MAJID EBRAHIMI WARKIANI

Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics

Publisher: MDPI AG

Date: 11-07-2022

DOI: 10.3390/CANCERS14143364

Abstract: Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min−1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF s les of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF s le in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

The Pandora’s Box of novel technologies that may revolutionize lung cancer

Publisher: Elsevier BV

Date: 09-2021

DOI: 10.1016/J.LUNGCAN.2021.06.022

Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D0RA04090H

Abstract: Mussel inspired ZIF8 microcarriers with high surface area, biocompatibility, and nanoscale surface roughness are applied to enhance mesenchymal stem cell attachment and proliferation in 3D cell culture.

Engineering miniaturized hair cell sensors for auditory system

Publisher: IEEE

Date: 2017

DOI: 10.1109/MEMSYS.2017.7863624

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

Publisher: Springer Science and Business Media LLC

Date: 13-09-2016

DOI: 10.1038/SREP32955

Abstract: We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.

Application of circulating tumour cells to predict response to treatment in head and neck cancer

Publisher: Springer Science and Business Media LLC

Date: 23-06-2022

DOI: 10.1007/S13402-022-00681-W

Abstract: Local recurrence and metastasis remain the major causes of death in head and neck cancer (HNC) patients. Circulating tumour cells (CTCs) are shed from primary and metastatic sites into the circulation system and have been reported to play critical roles in the metastasis and recurrence of HNC. Here, we explored the use of CTCs to predict the response to treatment and disease progression in HNC patients. Blood s les were collected at diagnosis from HNC patients (n = 119). CTCs were isolated using a spiral microfluidic device and were identified using immunofluorescence staining. Correlation of baseline CTC numbers to 13-week PET-CT data and multidisciplinary team consensus data were conducted. CTCs were detected in 60/119 (50.4%) of treatment naïve HNC patients at diagnosis. Baseline CTC numbers were higher in stage III vs. stage I-II p16-positive oropharyngeal cancers (OPCs) and other HNCs ( p = 0.0143 and 0.032, respectively). In addition, we found that baseline CTC numbers may serve as independent predictors of treatment response, even after adjusting for other conventional prognostic factors. CTCs were detected in 10 out of 11 patients exhibiting incomplete treatment responses. We found that baseline CTC numbers are correlated with treatment response in patients with HNC. The expression level of cell-surface vimentin (CSV) on CTCs was significantly higher in patients with persistent or progressive disease, thus providing additional prognostic information for stratifying the risk at diagnosis in HNC patients. The ability to detect CTCs at diagnosis allows more accurate risk stratification, which in the future may be translated into better patient selection for treatment intensification and/or de-intensification strategies.

Prognostic value of integrating circulating tumour cells and cell-free DNA in non-small cell lung cancer.

Publisher: Elsevier BV

Date: 07-2022

DOI: 10.1016/J.HELIYON.2022.E09971

Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells.

Publisher: Royal Society of Chemistry (RSC)

Date: 2014

DOI: 10.1039/C3LC50617G

Abstract: The enumeration and characterization of circulating tumor cells (CTCs), found in the peripheral blood of cancer patients, provide a potentially accessible source for cancer diagnosis and prognosis. This work reports on a novel spiral microfluidic device with a trapezoidal cross-section for ultra-fast, label-free enrichment of CTCs from clinically relevant blood volumes. The technique utilizes the inherent Dean vortex flows present in curvilinear microchannels under continuous flow, along with inertial lift forces which focus larger CTCs against the inner wall. Using a trapezoidal cross-section as opposed to a traditional rectangular cross-section, the position of the Dean vortex core can be altered to achieve separation. Smaller hematologic components are trapped in the Dean vortices skewed towards the outer channel walls and eventually removed at the outer outlet, while the larger CTCs equilibrate near the inner channel wall and are collected from the inner outlet. By using a single spiral microchannel with one inlet and two outlets, we have successfully isolated and recovered more than 80% of the tested cancer cell line cells (MCF-7, T24 and MDA-MB-231) spiked in 7.5 mL of blood within 8 min with extremely high purity (400-680 WBCs mL(-1) ~4 log depletion of WBCs). Putative CTCs were detected and isolated from 100% of the patient s les (n = 10) with advanced stage metastatic breast and lung cancer using standard biomarkers (CK, CD45 and DAPI) with the frequencies ranging from 3-125 CTCs mL(-1). We expect this simple and elegant approach can surmount the shortcomings of traditional affinity-based CTC isolation techniques as well as enable fundamental studies on CTCs to guide treatment and enhance patient care.

A Biomimetic Microfluidic Selection Platform Providing Improved Sperm Quality Metrics Compared to Swim-Up

Publisher: Research Square Platform LLC

Date: 16-09-2022

DOI: 10.21203/RS.3.RS-1993459/V1

Abstract: Sperm Selection is an essential component of all Assisted Reproductive Treatments (ART), and is by far and large the most neglected step in the ART workflow when it comes to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies and levels of DNA integrity Gold-standard techniques Density Gradient Centrifugation (DGC) and Swim Up (SU) have been proven to induce DNA fragmentation through the introduction of reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey towards selection. Sperm are first selected based on their motility and boundary following behavior, then on their expression of apoptotic markers, yielding over 68% more motile sperm than previously reported methods within a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results demonstrate an easy-to-use platform for sperm selection mimicking the biological function of the female reproductive tract during conception.

Circulating Tumour Cell Isolation and Molecular Profiling; Potential Therapeutic Intervention

Publisher: Springer International Publishing

Date: 2023

DOI: 10.1007/978-3-031-22903-9_14

Isolation of circulating tumor cells from seminal fluid of patients with prostate cancer using inertial microfluidics

Publisher: Research Square Platform LLC

Date: 11-03-2022

DOI: 10.21203/RS.3.RS-1399684/V1

Abstract: Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving the efficiency and throughput as high as 82% and ~ 1.7 mL min − 1 , respectively, while 99% of sperm cells was disposed of. The introduced approach was further tested in clinical setting by collecting and processing SF s les of PCa patients. The yield of isolated CTCs was measured as high as 613 cells per SF s le in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC amounts with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise of the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

Volume-preserving strategies to improve the mixing efficiency of serpentine micromixers

Publisher: IOP Publishing

Date: 30-09-2020

DOI: 10.1088/1361-6439/ABB8C2

Abstract: In this study, we have proposed volume-preserving strategies to boost chaoticadvection and improve the mixing efficiency of serpentine micromixers. The proposed strategies revolve around the point that the volume of the micromixer is kept constant during the manipulation. The first strategy involves the utilization of a nozzle-diffuser (ND) shaped microchannel. Using this, the velocity of the fluids fluctuates in an alternating pattern, leading to additional chaotic advection, a decrease in the mixing path, and an increase in the mixing index. The second strategy uses non-aligned inlets to generate swirl inducing effects at the microchannel entrance, where the collision of two fluids generates angular momentum in the flow, providing more chaotic advection. These strategies proved to be effective in boosting the mixing efficiency over wide ranges of Re in which 60% enhancement (from 20.53% to 80.31%) was achieved for Re of 30 by applying an ND shaped microchannel, and 20% enhancement (from 12.71% to 32.21%) was achieved for a critical Re of 15 by applying both of the strategies simultaneously.

Rapid and label-free isolation of tumour cells from the urine of patients with localised prostate cancer using inertial microfluidics

Publisher: MDPI AG

Date: 29-12-2020

DOI: 10.3390/CANCERS12010081

Abstract: During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco’s phosphate-buffered saline s le, where it demonstrated (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa—Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.

A 3D-printed microfluidic platform for simulating the effects of CPAP on the nasal epithelium

Publisher: IOP Publishing

Date: 08-04-2021

DOI: 10.1088/1758-5090/ABE4C1

Abstract: Obstructive sleep apnea (OSA) is a chronic disorder that involves a decrease or complete cessation of airflow during sleep. It occurs when the muscles supporting the soft tissues in the throat relax during sleep, causing narrowing or closure of the upper airway. Sleep apnea is a serious medical condition with an increased risk of cardiovascular complications and impaired quality of life. Continuous positive airway pressure (CPAP) is the most effective treatment for moderate to severe cases of OSA and is effective in mild sleep apnea. However, CPAP therapy is associated with the development of several nasal side effects and is inconvenient for the user, leading to low compliance rates. The effects of CPAP treatment on the upper respiratory system, as well as the pathogenesis of side effects, are incompletely understood and not adequately researched. To better understand the effects of CPAP treatment on the upper respiratory system, we developed an in vitro 3D-printed microfluidic platform. A nasal epithelial cell line, RPMI 2650, was then exposed to certain conditions to mimic the in vivo environment. To create these conditions, the microfluidic device was utilized to expose nasal epithelial cells grown and differentiated at the air–liquid interface. The airflow was similar to what is experienced with CPAP, with pressure ranging between 0 and 20 cm of H 2 O. Cells exposed to pressure showed decreased barrier integrity, change in cellular shape, and increased cell death (lactate dehydrogenase release into media) compared to unstressed cells. Stressed cells also showed increased secretions of inflammatory markers IL-6 and IL-8 and had increased production of ATP. Our results suggest that stress induced by airflow leads to structural, metabolic, and inflammatory changes in the nasal epithelium, which may be responsible for developing nasal side-effects following CPAP treatment.

Ex vivo culture of circulating tumour cells derived from non-small cell lung cancer

Publisher: AME Publishing Company

Date: 10-2020

DOI: 10.21037/TLCR-20-521

A microfluidic approach to rapid sperm recovery from heterogeneous cell suspensions

Publisher: Springer Science and Business Media LLC

Date: 12-04-2021

DOI: 10.1038/S41598-021-87046-9

Abstract: The isolation of sperm cells from background cell populations and debris is an essential step in all assisted reproductive technologies. Conventional techniques for sperm recovery from testicular sperm extractions stagnate at the s le processing stage, where it can take several hours to identify viable sperm from a background of collateral cells such as white bloods cells (WBCs), red blood cells (RBCs), epithelial cells (ECs) and in some cases cancer cells. Manual identification of sperm from contaminating cells and debris is a tedious and time-consuming operation that can be suitably addressed through inertial microfluidics. Microfluidics has proven an effective technology for high-quality sperm selection based on motility. However, motility-based selection methods cannot cater for viable, non-motile sperm often present in testicular or epididymal sperm extractions and aspirations. This study demonstrates the use of a 3D printed inertial microfluidic device for the separation of sperm cells from a mixed suspension of WBCs, RBCs, ECs, and leukemic cancer cells. This technology presents a 36-fold time improvement for the recovery of sperm cells ( 96%) by separating sperm, RBCS, WBCs, ECs and cancer cells into tight bands in less than 5 min. Furthermore, microfluidic processing of sperm has no impact on sperm parameters vitality, motility, morphology, or DNA fragmentation of sperm. Applying inertial microfluidics for non-motile sperm recovery can greatly improve the current processing procedure of testicular sperm extractions, simplifying the fertility outcomes for severe forms of male infertility that warrant the surgery.

Static droplet array for culturing single live adherent cells in an isolated chemical microenvironment

Publisher: Royal Society of Chemistry (RSC)

Date: 2018

DOI: 10.1039/C8LC00403J

Abstract: Rapid and reliable capture and analysis of single cells in a chemically isolated static droplet array for fast-tracking single cell discoveries.

A Reappraisal of Circulating Fetal Cell Noninvasive Prenatal Testing.

Publisher: Elsevier BV

Date: 06-2019

DOI: 10.1016/J.TIBTECH.2018.11.001

Abstract: New tools for higher-resolution fetal genome analysis including microarray and next-generation sequencing have revolutionized prenatal screening. This article provides commentary on this rapidly advancing field and a future perspective emphasizing circulating fetal cell (CFC) utility. Despite the tremendous technological challenges associated with their reliable and cost-effective isolation from maternal blood, CFCs have a strong potential to bridge the gap between the diagnostic sensitivity of invasive procedures and the desirable noninvasive nature of cell-free fetal DNA (cffDNA). Considering the rapid advances in both rare cell isolation and low-input DNA analysis, we argue here that CFC-based noninvasive prenatal testing is poised to be implemented clinically in the near future.

Microfluidics for Porous Systems: Fabrication, Microscopy and Applications

Publisher: Springer Science and Business Media LLC

Date: 26-11-2018

DOI: 10.1007/S11242-018-1202-3

Development of a Biomimetic semicircular canal with MEMS sensors to restore balance

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 12-2019

DOI: 10.1109/JSEN.2019.2935480

Ultra-high throughput microfluidic concentrator for harvesting of Tetraselmis sp. (Chlorodendrophyceae, Chlorophyta)

Publisher: Elsevier BV

Date: 05-2023

DOI: 10.1016/J.ALGAL.2023.103145

Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture.

Publisher: Springer Science and Business Media LLC

Date: 27-07-2017

DOI: 10.1038/S41598-017-06949-8

Abstract: Continuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. Current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. We introduce a novel cell retention device based on inertial sorting for perfusion culture of suspended mammalian cells. The device was characterized in terms of cell retention capacity, biocompatibility, scalability, and long-term reliability. This technology was demonstrated using a high concentration ( million cells/mL) perfusion culture of an IgG 1 -producing Chinese hamster ovary (CHO) cell line for 18–25 days. The device demonstrated reliable and clog-free cell retention, high IgG 1 recovery ( %) and cell viability ( %). Lab-scale perfusion cultures (350 mL) were used to demonstrate the technology, which can be scaled-out with parallel devices to enable larger scale operation. The new cell retention device is thus ideal for rapid perfusion process development in a biomanufacturing workflow.

Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer

Publisher: MDPI AG

Date: 31-07-2021

DOI: 10.3390/CANCERS13153869

Abstract: Keratins are the main identification markers of circulating tumor cells (CTCs) however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 (KRT16) mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer. By performing RT-qPCR, western blot, and immunocytochemistry, we investigated the expression patterns of K16 in metastatic breast cancer cell lines and evaluated the clinical relevance of K16 expression in CTCs of 20 metastatic breast cancer patients. High K16 protein expression was associated with an intermediate mesenchymal phenotype. Functional studies showed that K16 has a regulatory effect on EMT and overexpression of K16 significantly enhanced cell motility (p 0.001). In metastatic breast cancer patients, 64.7% of the detected CTCs expressed K16, which was associated with shorter relapse-free survival (p = 0.0042). Our findings imply that K16 is a metastasis-associated protein that promotes EMT and acts as a positive regulator of cellular motility. Furthermore, determining K16 status in CTCs provides prognostic information that helps to identify patients whose tumors are more prone to metastasize.

The Prognostic Role of Circulating Tumor Cells (CTCs) in Lung Cancer

Publisher: Frontiers Media SA

Date: 14-08-2018

DOI: 10.3389/FONC.2018.00311

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

Publisher: Impact Journals, LLC

Date: 27-06-2017

DOI: 10.18632/ONCOTARGET.18641

AI facilitated sperm detection in azoospermic samples for use in ICSI

Publisher: Cold Spring Harbor Laboratory

Date: 25-10-2023

DOI: 10.1101/2023.10.25.23297520

Decellularized human amniotic membrane reinforced by MoS₂-Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering

Publisher: SAGE Publications

Date: 25-01-2022

DOI: 10.1177/08853282211063289

Abstract: In order to regenerate myocardial tissues with functional characteristics, we need to copy some properties of the myocardium, such as its extracellular matrix and electrical conductivity. In this study, we synthesized nanosheets of Molybdenum disulfide (MoS 2 ), and integrated them into polycaprolactone (PCL) and electrospun on the surface of decellularized human amniotic membrane (DHAM) with the purpose of improving the scaffolds mechanical properties and electrical conductivity. For in vitro studies, we seeded the mouse embryonic cardiac cells, mouse Embryonic Cardiac Cells (mECCs), on the scaffolds and then studied the MoS 2 nanocomposites by scanning electron microscopy and Raman spectroscopy. In addition, we characterized the DHAM/PCL and DHAM/PCL-MoS 2 by SEM, transmission electron microscopy, water contact angle measurement, electrical conductivity, and tensile test. Besides, we confirmed the scaffolds are biocompatible by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT assay. Furthermore, by means of SEM images, it was shown that mECCs attached to the DHAM/PCL-MoS 2 scaffold have more cell aggregations and elongated morphology. Furthermore, through the Real-Time PCR and immunostaining studies, we found out cardiac genes were maturated and upregulated, and they also included GATA-4, c-TnT, NKX 2.5, and alpha-myosin heavy chain in cells cultured on DHAM/PCL-MoS 2 scaffold in comparison to DHAM/PCL and DHAM. Therefore, in terms of cardiac tissue engineering, DHAM nanofibrous scaffolds reinforced by PCL-MoS 2 can be suggested as a proper candidate.

Mesenchymal stem cells induce PD-L1 expression through the secretion of CCL5 in breast cancer cells

Publisher: Wiley

Date: 04-11-2021

DOI: 10.1002/JCP.30135

Abstract: Various factors in the tumor microenvironment (TME) regulate the expression of PD‐L1 in cancer cells. In TME, mesenchymal stem cells (MSCs) play a crucial role in tumor progression, metastasis, and drug resistance. Emerging evidence suggests that MSCs can modulate the immune‐suppression capacity of TME through the stimulation of PD‐L1 expression in various cancers nonetheless, their role in the induction of PD‐L1 in breast cancer remained elusive. Here, we assessed the potential of MSCs in the stimulation of PD‐L1 expression in a low PD‐L1 breast cancer cell line and explored its associated cytokine. We assessed the expression of MSCs‐related genes and their correlation with PD‐L1 across 1826 breast cancer patients from the METABRIC cohort. After culturing an ER+/differentiated/low PD‐L1 breast cancer cells with MSCs conditioned‐medium (MSC‐CM) in a microfluidic device, a variety of in‐vitro assays was carried out to determine the role of MSC‐CM in breast cancer cells' phenotype plasticity, invasion, and its effects on induction of PD‐L1 expression. In‐silico analysis showed a positive association between MSCs‐related genes and PD‐L1 expression in various types of breast cancer. Through functional assays, we revealed that MSC‐CM not only prompts a phenotype switch but also stimulates PD‐L1 expression at the protein level through secretion of various cytokines, especially CCL5. Treatment of MSCs with cytokine inhibitor pirfenidone showed a significant reduction in the secretion of CCL5 and consequently, expression of PD‐L1 in breast cancer cells. We concluded that MSCs‐derived CCL5 may act as a PD‐L1 stimulator in breast cancer.

Effects of sample rheology on the equilibrium position of particles and cells within a spiral microfluidic channel

Publisher: Springer Science and Business Media LLC

Date: 10-08-2021

DOI: 10.1007/S10404-021-02475-2

Advancing techniques and insights in circulating tumor cell (CTC) research

Publisher: Springer International Publishing

Date: 10-12-2017

DOI: 10.1007/978-3-319-45397-2_5

A miniaturized piezoresistive flow sensor for real‐time monitoring of intravenous infusion

Publisher: Wiley

Date: 20-05-2019

DOI: 10.1002/JBM.B.34412

Abstract: Drug overdose (DO) is considered one of the current issues of intravenous (IV) infusion particularly resulting in serious injuries and deaths. Malfunction of infusion pumps is reported as the main cause of the drug overdose. Live monitoring and flow rate calculation by health professionals have been practicing to avoid DO. However, human errors and miscalculations are inevitable. A secondary measurement tool is required to avoid the risk of OD when infusion pump malfunctions cannot be detected immediately. Here, inspired by nature, we developed a real-time monitoring device through which an administrator can review, evaluate, and modify the IV infusion process. Our flow sensor possesses an erected polymer hair cell on a multi-layered silicon base forming from a patterned gold strained gauge layer on a piezoresistive liquid crystal polymer (LCP) membrane. Gold strain gauges on an LCP membrane have been used instead of a piezoresistive silicon membrane as the sensing element. The combination of gold strain gauges and LCP membrane provides better sensitivity than a piezoresistive silicon membrane of the same dimensions and thickness. We also miniaturized our biocompatible sensor such that it can be possible to install it inside the IV tube in contact with the liquid providing an in-suite online flow monitoring. The proposed LCP membrane sensor is compared with two commercially available IV sensors to validate its flow sensing ability. The experimental results demonstrate that the proposed sensor provides a low threshold detection limit of 5 mL/hr, which betters the performance of other commercial sensors at low flow rates.

Alkaline Surfactant Polymer Flooding: What Happens at the Pore Scale?

Publisher: SPE

Date: 12-06-2017

DOI: 10.2118/185832-MS

Abstract: Alkaline-surfactant-polymer (ASP) flooding is a Chemical Enhanced Oil Recovery (CEOR) method whereby alkali, surfactant and polymer are injected as the same slug. It is one of the most promising world-wide focus of CEOR research and field trials, due to the unique synergy of the three chemical components. Polymers increase the viscosity of injected water, which improves macroscopic sweep efficiency by stabilizing the displacing front and counteracting heterogeneity effects. Surfactants, on the other hand, decrease the interfacial tension between the injected water and crude oil, which improves microscopic displacement efficiency by mobilizing trapped oil. Alkaline chemicals generate soap when reacting with crude oil, which reduces surfactant adsorption to grain surfaces. To fully understand the flow mechanisms in oil reservoirs and develop efficient recovery methods, it is essential to recognize the physics at the pore scale since this is the length scale at which capillary-trapped oil is mobilized. We developed an experimental micro-scale approach in which oil recovery is analyzed using microfluidics. The micromodels are fabricated based on: (1) a pore network generated via a Delaunay triangulation with an average pore size of 60 µm, (2) X-ray micro-Computed Tomography images of Bentheimer sandstone with resolution of 4.95 µm, and (3) a fractured network with a porosity of 10%. The networks are etched into silicon wafers and used to fabricate polydimethylsiloxane (PDMS) microfluidic devices. We compare not only oil recovery with ASP flooding between different porous networks but we also study displacement mechanisms and pore scale emulsion formation for ASP formulations that exhibit Winsor Type II+, II- and III behaviour. Our studies elucidate micro-scale oil recovery mechanisms for different ASP flooding scenarios. Our results provide direct visualization of the micro-scale phenomena occurring during ASP flooding and will guide further studies to target effective ASP flooding scenarios.

Surface modification of micro/nano-fabricated filters

Publisher: Trans Tech Publications, Ltd.

Date: 03-2012

DOI: 10.4028/WWW.SCIENTIFIC.NET/KEM.508.87

Abstract: Polymeric Micro-Fabricated Filters Have Excellent Sieving Properties. Their Identical Properties such as High Surface Porosity and Perfectly Patterned Pore Structure, which Is Combined with Mechanical Strength Make them Ideal for many Applications such as Microorganism Removal, Blood Filtration and Protein Purification. To Improve the Performance of the Micro-Fabricated Filters, we Employed Oxygen Plasma Treatment to Increase the Surface Hydrophilicity and Reduce the Membrane Fouling during Microfiltration. Hydrophilization and Integrity of the Surfaces Were Analyzed by Contact Angle Measurements and Topographic Imaging with an Atomic Force Microscope (AFM). Treatment of Polymeric Membranes with Oxygen Plasma Led to a Stable Hydrophilization and an Increased Surface Roughness. The Filtration Properties of the Modified and Unmodified Membranes Were Examined Using Clay Particles. A Significant Increase in Total Collected Volume of Filtrate Was Observed for the Treated Membranes during Filtration of Simulated Drinking Water S les Using Clay Suspension.

NEW 3D MULTICELLULAR MODELS OF PLACENTAL TISSUE FOR STUDYING IMPORTANT MECHANISMS OF PREECLAMPSIA

Publisher: Elsevier BV

Date: 09-2023

DOI: 10.1016/J.PLACENTA.2023.07.035

Selective separation of microalgae cells using inertial microfluidics

Publisher: Elsevier BV

Date: 03-2018

DOI: 10.1016/J.BIORTECH.2017.12.065

Abstract: Microalgae represent the most promising new source of biomass for the world's growing demands. However, the biomass productivity and quality is significantly decreased by the presence of bacteria or other invading microalgae species in the cultures. We therefore report a low-cost spiral-microchannel that can effectively separate and purify Tetraselmis suecica (lipid-rich microalgae) cultures from Phaeodactylum tricornutum (invasive diatom). Fluorescent polystyrene-microbeads of 6 μm and 10 μm diameters were first used as surrogate particles to optimize the microchannel design by mimicking the microalgae cell behaviour. Using the optimum flowrate, up to 95% of the P. tricornutum cells were separated from the culture without affecting the cell viability. This study shows, for the first time, the potential of inertial microfluidics to sort microalgae species with minimal size difference. Additionally, this approach can also be applied as a pre-sorting technique for water quality analysis.

Evaluation of Nanofiber PLA Scaffolds Using Dry- and Wet-Electrospinning Methods

Publisher: IEEE

Date: 11-2018

DOI: 10.1109/ICBME.2017.8430270

High-Plex and High-Throughput Digital Spatial Profiling of Non-Small-Cell Lung Cancer (NSCLC)

Publisher: MDPI AG

Date: 27-11-2020

DOI: 10.3390/CANCERS12123551

Abstract: Profiling the tumour microenvironment (TME) has been informative in understanding the underlying tumour–immune interactions. Multiplex immunohistochemistry (mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX Digital Spatial Profiler (DSP) platform to profile a non-small-cell lung cancer (NSCLC) tissue microarray for protein markers across immune cell profiling, immuno-oncology (IO) drug targets, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest (ROIs) were selected that described tumour, TME, and normal adjacent tissue (NAT) compartments. Our data revealed that paired analysis (n = 18) of matched patient compartments indicate that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to the tumour. Unmatched analysis indicated that the NAT (n = 19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1, and PTEN when compared to the TME (n = 32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3 (hazard ratio (HR): 0.5, p = 0.018), CD34 (HR: 0.53, p = 0.004), and ICOS (HR: 0.6, p = 0.047) in tumour compartments were significantly associated with improved overall survival (OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy s les, and demonstrate the power of such tools for a new generation of pathology research.

Biological diagnosis based on microfluidics and nanotechnology

Publisher: Wiley

Date: 27-12-2020

DOI: 10.1002/9783527818341.CH7

Attenuation of Cigarette-Smoke-Induced Oxidative Stress, Senescence, and Inflammation by Berberine-Loaded Liquid Crystalline Nanoparticles: In Vitro Study in 16HBE and RAW264.7 Cells

Publisher: MDPI AG

Date: 28-04-2022

DOI: 10.3390/ANTIOX11050873

Abstract: Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary disease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress and airway inflammation that further exacerbate disease progression. Generally, the broncho-epithelial cells and alveolar macrophages exposed to cigarette smoke release massive amounts of oxidative stress and inflammation mediators. Chronic exposure of cigarette smoke leads to premature senescence of airway epithelial cells. This impairs cellular function and ultimately leads to the progression of chronic lung diseases. Therefore, an ideal therapeutic candidate should prevent disease progression by controlling oxidative stress, inflammation, and senescence during the initial stage of damage. In our study, we explored if berberine (an alkaloid)-loaded liquid crystalline nanoparticles (berberine-LCNs)-based treatment to human broncho-epithelial cells and macrophage inhibits oxidative stress, inflammation, and senescence induced by cigarette-smoke extract. The developed berberine-LCNs were found to have favourable physiochemical parameters, such as high entrapment efficiency and sustained in vitro release. The cellular-assay observations revealed that berberine-LCNs showed potent antioxidant activity by suppressing the generation of reactive oxygen species in both broncho-epithelial cells (16HBE) and macrophages (RAW264.7), and modulating the genes involved in inflammation and oxidative stress. Similarly, in 16HBE cells, berberine-LCNs inhibited the cigarette smoke-induced senescence as revealed by X-gal staining, gene expression of CDKN1A (p21), and immunofluorescent staining of p21. Further in-depth mechanistic investigations into antioxidative, anti-inflammatory, and antisenescence research will ersify the current findings of berberine as a promising therapeutic approach for inflammatory lung diseases caused by cigarette smoking.

A Portable RT-LAMP/CRISPR Machine for Rapid COVID-19 Screening

Publisher: MDPI AG

Date: 02-10-2021

DOI: 10.3390/BIOS11100369

Abstract: The COVID-19 pandemic has changed people’s lives and has brought society to a sudden standstill, with lockdowns and social distancing as the preferred preventative measures. To lift these measurements and reduce society’s burden, developing an easy-to-use, rapid, and portable system to detect SARS-CoV-2 is mandatory. To this end, we developed a portable and semi-automated device for SARS-CoV-2 detection based on reverse transcription loop-mediated isothermal lification followed by a CRISPR/Cas12a reaction. The device contains a heater element mounted on a printed circuit board, a cooler fan, a proportional integral derivative controller to control the temperature, and designated areas for 0.2 mL Eppendorf® PCR tubes. Our system has a limit of detection of 35 copies of the virus per microliter, which is significant and has the capability of being used in crisis centers, mobile laboratories, remote locations, or airports to diagnose in iduals infected with SARS-CoV-2. We believe the current methodology that we have implemented in this article is beneficial for the early screening of infectious diseases, in which fast screening with high accuracy is necessary.

Lattice-Boltzmann modelling for inertial particle microfluidics applications - a tutorial review

Publisher: Informa UK Limited

Date: 24-09-2023

DOI: 10.1080/23746149.2023.2246704

Artificial fish skin of self-powered micro-electromechanical systems hair cells for sensing hydrodynamic flow phenomena

Publisher: The Royal Society

Date: 10-2015

DOI: 10.1098/RSIF.2015.0322

Abstract: Using biological sensors, aquatic animals like fishes are capable of performing impressive behaviours such as super-manoeuvrability, hydrodynamic flow ‘vision’ and object localization with a success unmatched by human-engineered technologies. Inspired by the multiple functionalities of the ubiquitous lateral-line sensors of fishes, we developed flexible and surface-mountable arrays of micro-electromechanical systems (MEMS) artificial hair cell flow sensors. This paper reports the development of the MEMS artificial versions of superficial and canal neuromasts and experimental characterization of their unique flow-sensing roles. Our MEMS flow sensors feature a stereolithographically fabricated polymer hair cell mounted on Pb(Zr 0.52 Ti 0.48 )O 3 micro-diaphragm with floating bottom electrode. Canal-inspired versions are developed by mounting a polymer canal with pores that guide external flows to the hair cells embedded in the canal. Experimental results conducted employing our MEMS artificial superficial neuromasts (SNs) demonstrated a high sensitivity and very low threshold detection limit of 22 mV/(mm s −1 ) and 8.2 µm s −1 , respectively, for an oscillating dipole stimulus vibrating at 35 Hz. Flexible arrays of such superficial sensors were demonstrated to localize an underwater dipole stimulus. Comparative experimental studies revealed a high-pass filtering nature of the canal encapsulated sensors with a cut-off frequency of 10 Hz and a flat frequency response of artificial SNs. Flexible arrays of self-powered, miniaturized, light-weight, low-cost and robust artificial lateral-line systems could enhance the capabilities of underwater vehicles.

Enhancing osteoregenerative potential of biphasic calcium phosphates by using bioinspired ZIF8 coating.

Publisher: Elsevier BV

Date: 04-2021

DOI: 10.1016/J.MSEC.2021.111972

Phenotypic Characterization of Circulating Lung Cancer Cells for Clinically Actionable Targets

Publisher: MDPI AG

Date: 18-03-2019

DOI: 10.3390/CANCERS11030380

Abstract: Objectives: In non-small cell lung cancers (NSCLC), tumour biopsy can often be an invasive procedure. The development of a non-invasive methodology to study genetic changes via circulating tumour cells (CTCs) is an appealing concept. Whilst CTCs typically remain as rare cells, improvements in epitope-independent CTC isolation techniques has given rise to a greater capture of CTCs. In this cross sectional study, we demonstrate the capture and characterization of NSCLC CTCs for the clinically actionable markers epidermal growth factor receptor (EGFR) alterations, anaplastic lymphoma kinase (ALK) rearrangements and programmed death ligand-1 (PD-L1) expression. The study identified CTCs/CTC clusters in 26/35 Stage IV NSCLC patients, and subsequently characterized the CTCs for EGFR mutation, ALK status and PD-L1 status. This pilot study demonstrates the potential of a non-invasive fluid biopsy to determine clinically relevant biomarkers in NSCLC.

Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro.

Publisher: Springer Science and Business Media LLC

Date: 13-07-2023

DOI: 10.1007/S00210-023-02603-5

Abstract: Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN , and metastasis-associated gene KRT18 . The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.

Understanding the tumor microenvironment in head and neck squamous cell carcinoma

Publisher: Wiley

Date: 2022

DOI: 10.1002/CTI2.1397

Abstract: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of tumors. While significant progress has been made using multimodal treatment, the 5‐year survival remains at 50%. Developing effective therapies, such as immunotherapy, will likely lead to better treatment of primary and metastatic disease. However, not all HNSCC tumors respond to immune checkpoint blockade therapy. Understanding the complex cellular composition and interactions of the tumor microenvironment is likely to lead to new knowledge for effective therapies and treatment resistance. In this review, we discuss HNSCC characteristics, predictive biomarkers, factors influencing immunotherapy response, with a focus on the tumor microenvironment.

A two-step microengineered system for high-density cell retention from bioreactors

Publisher: Elsevier BV

Date: 2021

DOI: 10.1016/J.SEPPUR.2020.117610

Lattice-Boltzmann Modelling for Inertial Particle Microfluidics Applications — A Tutorial Review

Publisher: Cold Spring Harbor Laboratory

Date: 10-04-2023

DOI: 10.1101/2023.04.10.536205

Abstract: Inertial particle microfluidics (IPMF) is an emerging technology for the manipulation and separation of microparticles and biological cells. Since the flow physics of IPMF is complex and experimental studies are often time-consuming or costly, computer simulations can offer complementary insights. In this tutorial review, we provide a guide for researchers who are exploring the potential of the lattice-Boltzmann (LB) method for simulating IPMF applications. We first review the existing literature to establish the state of the art of LB-based IPMF modelling. After summarising the physics of IPMF, we then present related methods used in LB models for IPMF and show several case studies of LB simulations for a range of IPMF scenarios. Finally, we conclude with an outlook and several proposed research directions.

ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration.

Publisher: Informa UK Limited

Date: 12-2020

DOI: 10.2147/IJN.S269169

Polymeric micro-filter manufactured by a dissolving mold technique

Publisher: IOP Publishing

Date: 21-05-2010

DOI: 10.1088/0960-1317/20/7/075005

Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA.

Publisher: American Chemical Society (ACS)

Date: 09-01-2023

DOI: 10.1021/ACS.ANALCHEM.2C04046

The Role of Circulating Biomarkers in Lung Cancer.

Publisher: Frontiers Media SA

Date: 21-01-2021

DOI: 10.3389/FONC.2021.801269

Abstract: Lung cancer is the leading cause of cancer morbidity and mortality worldwide and early diagnosis is crucial for the management and treatment of this disease. Non-invasive means of determining tumour information is an appealing diagnostic approach for lung cancers as often accessing and removing tumour tissue can be a limiting factor. In recent years, liquid biopsies have been developed to explore potential circulating tumour biomarkers which are considered reliable surrogates for understanding tumour biology in a non-invasive manner. Most common components assessed in liquid biopsy include circulating tumour cells (CTCs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), microRNA and exosomes. This review explores the clinical use of circulating tumour biomarkers found in liquid biopsy for screening, early diagnosis and prognostication of lung cancer patients.

Flow-induced stress on adherent cells in microfluidic devices

Publisher: Royal Society of Chemistry (RSC)

Date: 2015

DOI: 10.1039/C5LC00633C

Abstract: The article describes flow-induced stress on adherent cells in microfluidics devices in light of ongoing discoveries in mechanobiology.

Isolation, characterization and expansion of circulating tumor cells in solid cancers

Publisher: American Association for Cancer Research (AACR)

Date: 07-2019

DOI: 10.1158/1538-7445.AM2019-1333

Abstract: Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an in idual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=300) and lung cancer (n=80) patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient s les which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR- lification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (PFS) (Hazard ratio [HR]: 4.946 95% confidence internal [CI]:1.571-15.57 P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159 95% [CI]:1.011-26.33 P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient’s body from 7/18 HNC s les (4/7 HPV-positive). Recently, we have preliminary data that suggests that PD-L1 is frequently expressed on CTCs in HNC and lung cancer and an immunoscore may be able to identify patients likely to benefit from immunotherapy-a current unmet clinical need. Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular ersity present within the tumor, understanding of the disease progression and testing of therapies. Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean-Paul Thiery, Ken O'Byrne, Chamindie Punyadeera. Isolation, characterization and expansion of circulating tumor cells in solid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019 2019 Mar 29-Apr 3 Atlanta, GA. Philadelphia (PA): AACR Cancer Res 2019 (13 Suppl):Abstract nr 1333.

SC3_3. FKBPL signalling in placental development and preeclampsia

Publisher: Elsevier BV

Date: 09-2023

DOI: 10.1016/J.PREGHY.2023.07.153

The Use of Microfluidic Technology for Cancer Applications and Liquid Biopsy

Publisher: MDPI AG

Date: 10-08-2018

DOI: 10.3390/MI9080397

Abstract: There is growing awareness for the need of early diagnostic tools to aid in point-of-care testing in cancer. Tumor biopsy remains the conventional means in which to s le a tumor and often presents with challenges and associated risks. Therefore, alternative sources of tumor biomarkers is needed. Liquid biopsy has gained attention due to its non-invasive s ling of tumor tissue and ability to serially assess disease via a simple blood draw over the course of treatment. Among the leading technologies developing liquid biopsy solutions, microfluidics has recently come to the fore. Microfluidic platforms offer cellular separation and analysis platforms that allow for high throughout, high sensitivity and specificity, low s le volumes and reagent costs and precise liquid controlling capabilities. These characteristics make microfluidic technology a promising tool in separating and analyzing circulating tumor biomarkers for diagnosis, prognosis and monitoring. In this review, the characteristics of three kinds of circulating tumor markers will be described in the context of cancer, circulating tumor cells (CTCs), exosomes, and circulating tumor DNA (ctDNA). The review will focus on how the introduction of microfluidic technologies has improved the separation and analysis of these circulating tumor markers.

Fundamentals and applications of inertial microfluidics: a review

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C5LC01159K

Abstract: We provide a comprehensive review describing the fundamental mechanisms of inertial microfluidics, structure design and applications in biology, medicine and industry.

Metal-Organic Framework-Enhanced ELISA Platform for Ultrasensitive Detection of PD-L1

Publisher: American Chemical Society (ACS)

Date: 02-06-2020

DOI: 10.1021/ACSABM.0C00227

Abstract: The programmed cell death ligand 1 (PD-L1) protein has emerged as a predictive cancer biomarker and sensitivity to immune checkpoint blockade-based cancer immunotherapies. Current technologies for the detection of protein-based biomarkers, including the enzyme-linked immunosorbent assay (ELISA), have limitations such as low sensitivity and limit of detection (LOD) in addition to degradation of antibodies in exposure to environmental changes such as temperature and pH. To address these issues, we have proposed a metal-organic framework (MOF)-based ELISA for the detection of the PD-L1. A protective coating based on Zeolitic Imidazolate Framework 8 (ZIF-8) MOF thin film and polydopamine-polyethylenimine (PDA-PEI) was introduced on an ELISA plate for the improvement of antibody immobilization. Sensitivity and LOD of the resulting platform were compared with a conventional ELISA kit, and the bioactivity of the antibody in the proposed immunoassay was investigated in response to various pH and temperature values. The LOD and sensitivity of the MOF-based PD-L1 ELISA were 225 and 15.12 times higher, respectively, compared with those of the commercial ELISA kit. The antibody@ZIF-8/PDA-PEI was stable up to 55 °C and the pH range 5-10. The proposed platform can provide sensitive detection for target proteins, in addition to being resistant to elevated temperature and pH. The proposed MOF-based ELISA has significant potential for the clinical and diagnostic studies.

Microfluidics for research and applications in oncology.

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C5AN00382B

Abstract: Cancer is currently one of the top non-communicable human diseases, and continual research and developmental efforts, particularly in microfluidics technology, are being made to better understand and manage this disease.

Emerging role of circulating tumor cells in immunotherapy

Publisher: Ivyspring International Publisher

Date: 2021

DOI: 10.7150/THNO.59677

Design and applications of MEMS flow sensors: A review

Publisher: Elsevier BV

Date: 08-2019

DOI: 10.1016/J.SNA.2019.06.020

Unidirectional intercellular communication on a microfluidic chip

Publisher: Elsevier BV

Date: 03-2021

DOI: 10.1016/J.BIOS.2020.112833

High-Plex and High-throughput Digital Spatial Profiling of non-small-cell lung cancer (NSCLC)

Publisher: Cold Spring Harbor Laboratory

Date: 24-07-2020

DOI: 10.1101/2020.07.22.20160325

Abstract: Profiling the tumour microenvironment(TME) has been informative in understanding the underlying tumour-immune interactions. Multiplex immunohistochemistry(mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX™ Digital Spatial Profiler (DSP) platform to profile a NSCLC tissue microarray for protein markers across immune cell profiling, immuno-oncology(IO) drug target, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest(ROIs) were selected that described tumour, TME and normal adjacent tissue(NAT) compartments. Our data revealed that paired analysis (n=18) of patient matched compartments indicated that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to tumour. Unmatched analysis indicated that the NAT(n=19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1 and PTEN when compared to the TME(n=32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3(HR:0.5, p=0.018), CD34(HR:0.53, p=0.004) and ICOS (HR:0.6, p=0.047) in tumour compartments were significantly associated with improved overall survival(OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy s les and demonstrate the power of such tools for a new generation of pathology research. The authors have declared that no conflict of interest exists.

Correction to Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA.

Publisher: American Chemical Society (ACS)

Date: 03-08-2023

DOI: 10.1021/ACS.ANALCHEM.3C03312

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

Publisher: Frontiers Media SA

Date: 05-01-2023

DOI: 10.3389/FIMMU.2022.1060438

Abstract: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients. We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For ex le, in the pandemic H1N1/09 influenza virus infection, IFI27- like genes were highly upregulated in the blood s les of severely infected patients. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Rapid separation of bacteria from primary nasal samples using inertial microfluidics.

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D2LC00794K

Abstract: Development of an inertial microfluidic device based on a zigzag configuration for rapid separation of bacteria from primary nasal s les.

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations.

Publisher: Wiley

Date: 25-04-2019

DOI: 10.1002/JBM.A.36670

Abstract: To date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA-MB-231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569-1581, 2019.

Spatial Transcriptomic Approaches for Understanding the Tumor Microenvironment (TME)

Publisher: Springer Nature Switzerland

Date: 2023

DOI: 10.1007/16833_2022_111

Electrically conductive nanomaterials for cardiac tissue engineering.

Publisher: Elsevier BV

Date: 04-2019

DOI: 10.1016/J.ADDR.2019.06.001

Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C6LC00713A

Abstract: Blood and blood products are critical components of health care.

High-throughput sorting of eggs for synchronization ofC. elegansin a microfluidic spiral chip

Publisher: Royal Society of Chemistry (RSC)

Date: 2018

DOI: 10.1039/C7LC00998D

Abstract: High-throughput isolation of C. elegans eggs from a mixed worm population in a spiral chip using inertial microfluidics.

Inertial Microfluidic Purification of CAR-T-Cell Products.

Publisher: Wiley

Date: 08-12-2022

DOI: 10.1002/ADBI.202101018

Abstract: Chimeric antigen receptor T (CAR-T) cell therapy is rapidly becoming a frontline cancer therapy. However, the manufacturing process is time-, labor- and cost-intensive, and it suffers from significant bottlenecks. Many CAR-T products fail to reach the viability release criteria set by regulators for commercial cell therapy products. This results in non-recoupable costs for the manufacturer and is detrimental to patients who may not receive their scheduled treatment or receive out-of-specification suboptimal formulation. It is demonstrated here that inertial microfluidics can, within minutes, efficiently deplete nonviable cells from low-viability CAR-T cell products. The percentage of viable cells increases from 40% (SD ± 0.12) to 71% (SD ± 0.09) for untransduced T cells and from 51% (SD ± 0.12) to 71% (SD ± 0.09) for CAR-T cells, which meets the clinical trials' release parameters. In addition, the processing of CAR-T cells formulated in CryStor yields a 91% reduction in the amount of the cryoprotectant dimethyl sulfoxide. Inertial microfluidic processing has no detrimental effects on the proliferation and cytotoxicity of CAR-T cells. Interestingly, ≈50% of T-regulatory and T-suppressor cells are depleted, suggesting the potential for inertial microfluidic processing to tune the phenotypical composition of T-cell products.

Upregulation of PD-L1 expression in breast cancer cells through the formation of 3D multicellular cancer aggregates under different chemical and mechanical conditions.

Publisher: Elsevier BV

Date: 12-2019

DOI: 10.1016/J.BBAMCR.2019.118526

Abstract: Expression of programmed death-ligand 1 (PD-L1) in cancer cells plays an important role in cancer-immune cell interaction. The emerging evidence suggests regulation of PD-L1 expression by several tumor microenvironmental cues. However, the association of PD-L1 expression with chemical and mechanical features of the tumor microenvironment, specifically epidermal growth factor receptor (EGFR) signaling and matrix stiffness, remains elusive. Herein, we determine whether EGFR targeting and substrate stiffness affect the regulation of PD-L1 expression. Breast carcinoma cell lines, MCF7 and MDA-MB-231, were cultured under different conditions targeting EGFR and exposing cells to distinct substrate stiffness to evaluate PD-L1 expression. Furthermore, the ability to form aggregates in short-term culture of breast carcinoma cells and its effect on expression level of PD-L1 was probed. Our results indicated that PD-L1 expression was altered in response to both EGFR inhibition and substrate stiffness. Additionally, a positive association between the formation of multicellular aggregates and PD-L1 expression was observed. MDA-MB-231 cells expressed the highest PD-L1 level on a stiff substrate, while inhibition of EGFR reduced expression of PD-L1. The results suggested that both physical and chemical features of tumor microenvironment regulate PD-L1 expression through alteration of tumor aggregate formation potential. In line with these results, the in-silico study highlighted a positive correlation between PD-L1 expression, EGFR signaling, epithelial to mesenchymal transition related transcription factors (EMT-TFs) and stemness markers in metastatic breast cancer. These findings improve our understanding of regulation of PD-L1 expression by tumor microenvironment leading to evasion of tumor cells from the immune system.

Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA.

Publisher: SAGE Publications

Date: 2023

DOI: 10.1177/17588359231192401

COVID-19 spread in a classroom equipped with partition – A CFD approach

Publisher: Elsevier BV

Date: 10-2021

DOI: 10.1016/J.JHAZMAT.2021.126587

Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature

Publisher: Wiley

Date: 07-03-2019

DOI: 10.1002/ADMT.201800726

Abstract 5572: Circulating tumor cells: The tumor trail left in the blood

Publisher: American Association for Cancer Research (AACR)

Date: 07-2018

DOI: 10.1158/1538-7445.AM2018-5572

Abstract: Background: Metastasis in HNC patients is reflected by measurable levels of circulating tumor cells (CTCs) in the peripheral blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an in idual patient. For patients without CTCs at presentation, the detection of CTCs in the blood and analysis of biomarkers within them provide an opportunity to identify patients "at risk" of developing overt metastasis, accelerating targeted treatment in addition to routing care with the clear aim of improving cure. Methods: Our study aimed to assess whether CTCs from the blood of HNC patients attending the Princess Alexandra Hospital and Royal Brisbane and Women's Hospital provided early cues of distant metastases (n=250). Results: With significant advances in CTC isolation technologies, we could demonstrate a higher CTC capture efficiency using epitope-independent platforms. By assessment of single and clustered CTCs, our data showed that HNC patients can be identified 4-6 months prior to developing clinical/radiographically evident metastasis. In these patients, a window for treatment escalation could become a possibility. In a proof-of-principle study, using novel culture formulations and hypoxic conditions (1-2% O2), we were able to demonstrate, for the first time, short-term patient-derived CTC cultures ex vivo from 7/18 HNC s les (4/7 HPV-positive, oropharyngeal) in a clinically relevant time period. Recent advancements have shown that PD-1 immune checkpoint therapies have durable responses in metastatic HNC patients that fail 1st- and 2nd-line therapy. Our preliminary data suggest PD-L1 is frequently expressed on HNC CTCs, and an immunoscore may be able to stratify patients likely to respond to immunotherapy. Conclusion: Expanding CTCs outside the patient's body allows for the recapitulation of the molecular ersity present within the tumor, understanding the disease progression and testing of therapies. Patients with a high percentage of PD-L1+ CTCs could be potential candidates for anti-PD-L1 therapy, a promising new immunotherapy. Citation Format: Arutha Kulasinghe, Chris Perry, Liz Kenny, Tony Blick, Majid Warkiani, Ian Vela, Ken O'Byrne, Jean-Paul Thiery, Erik Thompson, Colleen Nelson, Chamindie Punyadeera. Circulating tumor cells: The tumor trail left in the blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018 2018 Apr 14-18 Chicago, IL. Philadelphia (PA): AACR Cancer Res 2018 (13 Suppl):Abstract nr 5572.

Coal-on-a-Chip: Visualizing Flow in Coal Fractures

Publisher: American Chemical Society (ACS)

Date: 25-09-2017

DOI: 10.1021/ACS.ENERGYFUELS.7B01046

Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics

Publisher: Elsevier BV

Date: 03-2023

DOI: 10.1016/J.BIOS.2022.114966

Strategically Designing a Pumpless Microfluidic Device on an inert Polypropylene Substrate with Potential Application in Biosensing and Diagnostics

Publisher: American Chemical Society (ACS)

Date: 22-05-2017

DOI: 10.1021/ACS.LANGMUIR.7B00537

Abstract: This study is an attempt to make a step forward to implement the very immature concept of pumpless transportation of liquid into a real miniaturized device or lab-on-chip (LOC) on a plastic substrate. "Inert" plastic materials such as polypropylene (PP) are used in a variety of biomedical applications but their surface engineering is very challenging. Here, it was demonstrated that with a facile innovative wettability patterning route using fluorosilanized UV-independent TiO

IFI27 transcription is an early predictor for COVID-19 outcomes; a multi-cohort observational study

Publisher: Cold Spring Harbor Laboratory

Date: 11-2021

DOI: 10.1101/2021.10.29.21265555

Abstract: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients. We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID-19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For ex le, in the pandemic H1N1/09 swine influenza virus infection, IFI27- like genes were highly upregulated in the blood s les of severely infected patients. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus. We searched the scientific literature using PubMed to identify studies that used the IFI27 biomarker to predict outcomes in COVID-19 patients. We used the search terms “ IFI27 ”, “COVID-19, “gene expression” and “outcome prediction”. We did not identify any study that investigated the role of IFI27 biomarker in outcome prediction. Although ten studies were identified using the general terms of “gene expression” and “COVID-19”, IFI27 was only mentioned in passing as one of the identified genes. All these studies addressed the broader question of the host response to COVID-19 none focused solely on using IFI27 to improve the risk stratification of infected patients in a pandemic. Here, we present the findings of a multi-cohort study of the IFI27 biomarker in COVID-19 patients. Our findings show that the host response, as reflected by blood IFI27 gene expression, accurately predicts COVID-19 disease progression (positive and negative predictive values 0.83 and 0.95, respectively), outperforming age, comorbidity, C-reactive protein and all other known risk factors. The strong association of IFI27 with disease severity occurs not only in SARS-CoV-2 infection, but also in other respiratory viruses with pandemic potential, such as the influenza virus. These findings suggest that host response biomarkers, such as IFI27 , could help identify high-risk COVID-19 patients - those who are more likely to develop infection complications - and therefore may help improve patient triage in a pandemic. This is the first systemic study of the clinical role of IFI27 in the current COVID-19 pandemic and its possible future application in other respiratory virus pandemics. The findings not only could help improve the current management of COVID-19 patients but may also improve future pandemic preparedness.

A rapid co-culture stamping device for studying intercellular communication

Publisher: Springer Science and Business Media LLC

Date: 18-10-2016

DOI: 10.1038/SREP35618

Abstract: Regulation of tissue development and repair depends on communication between neighbouring cells. Recent advances in cell micro-contact printing and microfluidics have facilitated the in-vitro study of homotypic and heterotypic cell-cell interaction. Nonetheless, these techniques are still complicated to perform and as a result, are seldom used by biologists. We report here development of a temporarily sealed microfluidic st ing device which utilizes a novel valve design for patterning two adherent cell lines with well-defined interlacing configurations to study cell-cell interactions. We demonstrate post-st ing cell viability of %, the st ing of multiple adherent cell types, and the ability to control the seeded cell density. We also show viability, proliferation and migration of cultured cells, enabling analysis of co-culture boundary conditions on cell fate. We also developed an in-vitro model of endothelial and cardiac stem cell interactions, which are thought to regulate coronary repair after myocardial injury. The st is fabricated using microfabrication techniques, is operated with a lab pipettor and uses very low reagent volumes of 20 μl with cell injection efficiency of %. This easy-to-use device provides a general strategy for micro-patterning of multiple cell types and will be important for studying cell-cell interactions in a multitude of applications.

Promoted chondrogenesis of hMCSs with controlled release of TGF-β3 via microfluidics synthesized alginate nanogels

Publisher: Elsevier BV

Date: 02-2020

DOI: 10.1016/J.CARBPOL.2019.115551

Abstract: The field of cartilage tissue engineering has been evolved in the last decade and a myriad of scaffolding biomaterials and bioactive agents have been proposed. Controlled release of growth factors encapsulated in the polymeric nanomaterials has been of interest notably for the repair of damaged articular cartilage. Here, we proposed an on-chip hydrodynamic flow focusing microfluidic approach for synthesis of alginate nanogels loaded with the transforming growth factor beta 3 (TGF-β3) through an ionic gelation method in order to achieve precise release profile of these bioactive agents during chondrogenic differentiation of mesenchymal stem cells (MSCs). Alginate nanogels with adjustable sizes were synthesized by fine-tuning the flow rate ratio (FRR) in the microfluidic device consisting of cross-junction microchannels. The result of present study showed that the proposed approach can be a promising tool to synthesize bioactive -loaded polymeric nanogels for applications in drug delivery and tissue engineering.

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Publisher: MDPI AG

Date: 13-10-2021

DOI: 10.3390/CANCERS13205118

Abstract: The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in s les with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in s les correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.

Experimental and numerical study of elasto-inertial focusing in straight channels.

Publisher: AIP Publishing

Date: 05-2019

DOI: 10.1063/1.5093345

Abstract: Elasto-inertial microfluidics has drawn significant attention in recent years due to its enhanced capabilities compared to pure inertial systems in control of small microparticles. Previous investigations have focused mainly on the applications of elasto-inertial sorting, rather than studying its fundamentals. This is because of the complexity of simulation and analysis, due to the presence of viscoelastic force. There have been some investigative efforts on the mechanisms of elasto-inertial focusing in straight channels however, these studies were limited to simple rectangular channels and neglected the effects of geometry and flow rates on focusing positions. Herein, for the first time, we experimentally and numerically explore the effects of elasticity accompanying channel cross-sectional geometry and s le flow rates on the focusing phenomenon in elasto-inertial systems. The results reveal that increasing the aspect ratio weakens the elastic force more than inertial force, causing a transition from one focusing position to two. In addition, they show that increasing the angle of a channel corner causes the elastic force to push the particles more efficiently toward the center over a larger area of the channel cross section. Following on from this, we proposed a new complex straight channel which demonstrates a tighter focusing band compared to other channel geometries. Finally, we focused Saccharomyces cerevisiae cells (3–5 μm) in the complex channel to showcase its capability in focusing small-size particles. We believe that this research work improves the understanding of focusing mechanisms in viscoelastic solutions and provides useful insights into the design of elasto-inertial microfluidic devices.

Malaria detection using inertial microfluidics.

Publisher: Royal Society of Chemistry (RSC)

Date: 2015

DOI: 10.1039/C4LC01058B

Abstract: Diagnosis of malaria at the early stage of infection is challenging due to the difficulty in detecting low abundance parasites from blood.

Immunotherapeutic targets in non‐small cell lung cancer

Publisher: Wiley

Date: 25-08-2022

DOI: 10.1111/IMM.13562

Abstract: Non‐small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5‐year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in‐depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.

Engineering a 3D microfluidic culture platform for tumor-treating field application.

Publisher: Springer Science and Business Media LLC

Date: 24-05-2016

DOI: 10.1038/SREP26584

Abstract: The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured in idually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo -like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.

A microfluidic framework for studying relative permeability in coal

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.COAL.2016.04.002

Application of level-set method in simulation of normal and cancer cells deformability within a microfluidic device.

Publisher: Elsevier BV

Date: 11-2020

DOI: 10.1016/J.JBIOMECH.2020.110066

Preparation of Iridescent 2D Photonic Crystals by Using a Mussel-Inspired Spatial Patterning of ZIF-8 with Potential Applications in Optical Switch and Chemical Sensor

Publisher: American Chemical Society (ACS)

Date: 19-10-2017

DOI: 10.1021/ACSAMI.7B13618

Abstract: In this work, spatial patterning of a thin, dense, zeolitic imidazolate framework (ZIF-8) pattern was generated using photolithography and nanoscale (60 nm) dopamine coating. A bioinspired, unique, reversible, two-color iridescent pattern can be easily obtained for potential applications in sensing and photonics.

Characterization of single polyvinylidene fluoride (PVDF) nanofiber for flow sensing applications

Publisher: AIP Publishing

Date: 10-2017

DOI: 10.1063/1.4994968

Abstract: The use of Polyvinylidene Fluoride (PVDF) based piezoelectric nanofibers for sensing and actuation has been reported widely in the past. However, in most cases, PVDF piezoelectric nanofiber mats have been used for sensing applications. This work fundamentally characterizes a single electrospun PVDF nanofiber and demonstrates its application as a sensing element for nanoelectromechanical sensors (NEMS). PVDF nanofiber mats were spun by far field electrospinning (FFES) process and complete material characterization was conducted by means of scanning electron microscope (SEM) imaging, Raman Spectroscopy and FTIR spectroscopy. An optimized recipe was developed for spinning a single suspended nanofiber on a specially designed MEMS substrate which allows the nano-mechanical and electrical characterization of a single PVDF nanofiber. Electrical characterization is conducted using a single suspended nanofiber to determine the piezoelectric coefficient (d33) of the nanofiber to be -58.77 pm/V. Also the mechanical characterization conducted using a nanoindenter revealed a Young’s Modulus and hardness of 2.2 GPa and 0.1 GPa respectively. Finally, an application that utilizes the single PVDF nanofiber as a sensing element to form a NEMS flow sensor is demonstrated. The single nanofiber flow sensor is tested in presence of various oscillatory flow conditions.

A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma

Publisher: Elsevier BV

Date: 08-2021

DOI: 10.1016/J.IJOM.2020.11.012

Improving capture efficiency of human cancer cell derived exosomes with nanostructured metal organic framework functionalized beads

Publisher: Elsevier BV

Date: 06-2021

DOI: 10.1016/J.APMT.2021.100994

Point of care diagnostics in the age of covid-19

Publisher: MDPI AG

Date: 23-12-2021

DOI: 10.3390/DIAGNOSTICS11010009

Abstract: The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times ( h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.

Axial localization and tracking of self-interference nanoparticles by lateral point spread functions

Publisher: Springer Science and Business Media LLC

Date: 04-2021

DOI: 10.1038/S41467-021-22283-0

Abstract: Sub-diffraction limited localization of fluorescent emitters is a key goal of microscopy imaging. Here, we report that single upconversion nanoparticles, containing multiple emission centres with random orientations, can generate a series of unique, bright and position-sensitive patterns in the spatial domain when placed on top of a mirror. Supported by our numerical simulation, we attribute this effect to the sum of each single emitter’s interference with its own mirror image. As a result, this configuration generates a series of sophisticated far-field point spread functions (PSFs), e.g. in Gaussian, doughnut and archery target shapes, strongly dependent on the phase difference between the emitter and its image. In this way, the axial locations of nanoparticles are transferred into far-field patterns. We demonstrate a real-time distance sensing technology with a localization accuracy of 2.8 nm, according to the atomic force microscope (AFM) characterization values, smaller than 1/350 of the excitation wavelength.

Micro-fabricated membranes with regular pores for efficient pathogen removal

Publisher: Springer International Publishing

Date: 2014

DOI: 10.1007/978-3-319-02913-9_108

An Efficient Graphene Quantum Dots-Based Electrochemical Cytosensor for the Sensitive Recognition of CD123 in Acute Myeloid Leukemia Cells

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 08-2021

DOI: 10.1109/JSEN.2021.3079224

Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.SNB.2018.01.223

Isolation of Circulating Fetal Trophoblasts Using Inertial Microfluidics for Noninvasive Prenatal Testing

Publisher: Wiley

Date: 14-06-2018

DOI: 10.1002/ADMT.201800066

Fabrication of unconventional inertial microfluidic channels using wax 3D printing.

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/C9SM02067E

Abstract: A novel workflow for the fabrication of inertial microfluidic devices based on the wax 3D printing method.

An easily fabricated three-dimensional threaded lemniscate-shaped micromixer for a wide range of flow rates

Publisher: AIP Publishing

Date: 2017

DOI: 10.1063/1.4974904

Abstract: Mixing fluid s les or reactants is a paramount function in the fields of micro total analysis system (μTAS) and microchemical processing. However, rapid and efficient fluid mixing is difficult to achieve inside microchannels because of the difficulty of diffusive mass transfer in the laminar regime of the typical microfluidic flows. It has been well recorded that the mixing efficiency can be boosted by migrating from two-dimensional (2D) to three-dimensional (3D) geometries. Although several 3D chaotic mixers have been designed, most of them offer a high mixing efficiency only in a very limited range of Reynolds numbers (Re). In this work, we developed a 3D fine-threaded lemniscate-shaped micromixer whose maximum numerical and empirical efficiency is around 97% and 93%, respectively, and maintains its high performance (i.e., & %) over a wide range of 1 & Re & 1000 which meets the requirements of both the μTAS and microchemical process applications. The 3D micromixer was designed based on two distinct mixing strategies, namely, the inducing of chaotic advection by the presence of Dean flow and diffusive mixing through thread-like grooves around the curved body of the mixers. First, a set of numerical simulations was performed to study the physics of the flow and to determine the essential geometrical parameters of the mixers. Second, a simple and cost-effective method was exploited to fabricate the convoluted structure of the micromixers through the removal of a 3D-printed wax structure from a block of cured polydimethylsiloxane. Finally, the fabricated mixers with different threads were tested using a fluorescent microscope demonstrating a good agreement with the results of the numerical simulation. We envisage that the strategy used in this work would expand the scope of the micromixer technology by broadening the range of efficient working flow rate and providing an easy way to the fabrication of 3D convoluted microstructures.

Biocatalytic micromixer coated with enzyme-MOF thin film for CO2 conversion to formic acid

Publisher: Elsevier BV

Date: 12-2021

DOI: 10.1016/J.CEJ.2021.130856

Computational inertial microfluidics: a review.

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/C9LC01022J

Abstract: Schematic illustration of various kinds of geometries used for inertial microfluidics.

Rapid separation and identification of beer spoilage bacteria by inertial microfluidics and MALDI-TOF mass spectrometry

Publisher: Royal Society of Chemistry (RSC)

Date: 2019

DOI: 10.1039/C9LC00152B

Abstract: Microfluidics and MALDI-TOF MS is a rapid, high-throughput, and accurate method for the identification of beer spoilage bacteria.

Mist harvesting using bioinspired polydopamine coating and microfabrication technology

Publisher: Elsevier BV

Date: 03-2018

DOI: 10.1016/J.DESAL.2017.12.023

A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells

Publisher: Wiley

Date: 11-03-2016

DOI: 10.1002/JBM.A.35689

Abstract: Controlling cellular orientation, proliferation, and differentiation is valuable in designing organ replacements and directing tissue regeneration. In the present study, we developed a hybrid microfluidic system to produce a dynamic microenvironment by placing aligned PDMS microgrooves on surface of biodegradable polymers as physical guidance cues for controlling the neural differentiation of human induced pluripotent stem cells (hiPSCs). The neuronal differentiation capacity of cultured hiPSCs in the microfluidic system and other control groups was investigated using quantitative real time PCR (qPCR) and immunocytochemistry. The functionally of differentiated hiPSCs inside hybrid system's scaffolds was also evaluated on the rat hemisected spinal cord in acute phase. Implanted cell's fate was examined using tissue freeze section and the functional recovery was evaluated according to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Our results confirmed the differentiation of hiPSCs to neuronal cells on the microfluidic device where the expression of neuronal-specific genes was significantly higher compared to those cultured on the other systems such as plain tissue culture dishes and scaffolds without fluidic channels. Although survival and integration of implanted hiPSCs did not lead to a significant functional recovery, we believe that combination of fluidic channels with nanofiber scaffolds provides a great microenvironment for neural tissue engineering, and can be used as a powerful tool for in situ monitoring of differentiation potential of various kinds of stem cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1534-1543, 2016.

Microengineered filters for efficient delivery of nanomaterials into mammalian cells.

Publisher: Springer Science and Business Media LLC

Date: 14-03-2022

DOI: 10.1038/S41598-022-08300-2

Abstract: Intracellular delivery of nanomaterials into the cells of interest has enabled cell manipulation for numerous applications ranging from cell-based therapies to biomedical research. To date, different carriers or membrane poration-based techniques have been developed to load nanomaterials to the cell interior. These biotools have shown promise to surpass the membrane barrier and provide access to the intracellular space followed by passive diffusion of exogenous cargoes. However, most of them suffer from inconsistent delivery, cytotoxicity, and expensive protocols, somewhat limiting their utility in a variety of delivery applications. Here, by leveraging the benefits of microengineered porous membranes with a suitable porosity, we demonstrated an efficient intracellular loading of erse nanomaterials to different cell types based on inducing mechanical disruption to the cell membrane. In this work, for the first time, we used ultra-thin silicon nitride (SiN) filter membranes with uniform micropores smaller than the cell diameter to load impermeable nanomaterials into adherent and non-adherent cell types. The delivery performance using SiN microsieves has been validated through the loading of functional nanomaterials from a few nanometers to hundreds of nanometers into mammalian cells with minimal undesired impacts. Besides the high delivery efficiency and improved cell viability, this simple and low-cost approach offers less clogging and higher throughput (10 7 cell min −1 ). Therefore, it yields to the efficient introduction of exogenous nanomaterials into the large population of cells, illustrating the potential of these microengineered filters to be widely used in the microfiltroporation (MFP) setup.

Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound-on-a-Chip Model.

Publisher: Wiley

Date: 04-12-2018

DOI: 10.1002/ADHM.201801307

Abstract: Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost-effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound-on-chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF-α) or by triculturing with macrophages. Both the approaches significantly increase IL-1β, IL-6, IL-8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti-inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound-on-chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti-inflammatory compounds.

Understanding the tumor microenvironment for effective immunotherapy

Publisher: Wiley

Date: 04-12-2020

DOI: 10.1002/MED.21765

The Use of Three-Dimensional DNA Fluorescent In Situ Hybridization (3D DNA FISH) for the Detection of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer (NSCLC) Circulating Tumor Cells

Publisher: MDPI AG

Date: 15-06-2020

DOI: 10.3390/CELLS9061465

Abstract: Tumor tissue biopsy is often limited for non-small cell lung cancer (NSCLC) patients and alternative sources of tumoral information are desirable to determine molecular alterations such as anaplastic lymphoma kinase (ALK) rearrangements. Circulating tumor cells (CTCs) are an appealing component of liquid biopsies, which can be s led serially over the course of treatment. In this study, we enrolled a cohort of ALK-positive (n = 8) and ALK-negative (n = 12) NSCLC patients, enriched for CTCs using spiral microfluidic technology and performed DNA fluorescent in situ hybridization (FISH) for ALK. CTCs were identified in 12/20 NSCLC patients ranging from 1 to 26 CTCs/7.5 mL blood. Our study revealed that 3D imaging of CTCs for ALK translocations captured a well-defined separation of 3′ and 5′ signals indicative of ALK translocations and overlapping 3′/5′ signal was easily resolved by imaging through the nuclear volume. This study provides proof-of-principle for the use of 3D DNA FISH in the determination of CTC ALK translocations in NSCLC.

A simple coating method of PDMS microchip with PTFE for synthesis of dexamethasone-encapsulated PLGA nanoparticles

Publisher: Springer Science and Business Media LLC

Date: 04-04-2019

DOI: 10.1007/S13346-019-00636-Z

Abstract: Dexamethasone is a widely used drug in medical and biological applications. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this anti-inflammatory drug in poly(lactic-co-glycolic acid) (PLGA) nanoparticles can minimize uncontrolled issues. As dexamethasone-encapsulated PLGA nanoparticles are synthesized in the presence of organic solvents, poly(dimethylsiloxane) (PDMS)-based microchannels collapse due to the swelling problem. In present study, PTFE nanoparticles were used for the surface modification of the microchannels to prevent absorption and adhesion of solvents into the microchannels' wall. The contact angle analysis of microchips after coating showed that the surface of microchannels bear the superhydrophobicity feature (140.30°) and SEM images revealed that PTFE covered the surface of PDMS, favorably. Then, the prepared microchip was tested for the synthesis of dexamethasone-loaded nanoparticles. SEM and atomic force microscopy (AFM) images of the synthesized nanoparticles represented that there was not any evidence of adhesion or absorption of nanoparticles. Furthermore, the monodispersity of nanoparticles was discernible. As AFM results revealed, the average diameters of 47, 63, and 82 nm were achieved for flow ratios of 0.01, 0.05, and 0.1, respectively. To evaluate the drug efficiency, cumulative release and encapsulation efficiency were analyzed which showed much more efficiency than the synthesized nanoparticles in the bulk mode. In addition, MTT test revealed that nanoparticles could be considered as a non-toxic material. Since the synthesis of drug-loaded nanoparticles is ubiquitous in laboratory experiments, the approach presented in this study can render more versatility in this regard.

Investigation of membrane fouling at the microscale using isopore filters

Publisher: Springer Science and Business Media LLC

Date: 31-12-2015

DOI: 10.1007/S10404-014-1538-0

A Novel Strategy for Square-Wave Micromixers: A Survey of RBC Lysis for Further Biological Analysis

Publisher: American Chemical Society (ACS)

Date: 02-10-2023

DOI: 10.1021/ACS.IECR.3C01336

Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions

Publisher: Springer Science and Business Media LLC

Date: 20-08-2018

DOI: 10.1038/S41598-018-31019-Y

Abstract: Rapidly evolving cell-based therapies towards clinical trials demand alternative approaches for efficient expansion of adherent cell types such as human mesenchymal stem cells (hMSCs). Using microcarriers (100–300 µm) in a stirred tank bioreactor offers considerably enhanced surface to volume ratio of culture environment. However, downstream purification of the harvested cell product needs to be addressed carefully due to distinctive features and fragility of these cell products. This work demonstrates a novel alternative approach which utilizes inertial focusing to separate microcarriers (MCs) from the final cell suspension. First, we systematically investigated MC focusing dynamics inside scaled-up curved channels with trapezoidal and rectangular cross-sections. A trapezoidal spiral channel with ultra-low-slope (Tan(α) = 0.0375) was found to contribute to strong MC focusing (~300 Re ~400) while managing high MC volume fractions up to ~1.68%. Accordingly, the high-throughput trapezoidal spiral channel successfully separated MCs from hMSC suspension with total cell yield~94% (after two passes) at a high volumetric flow rate of ~30 mL/min (Re~326.5).

Dryland communities find little refuge from grazing due to long-term changes in water availability

Publisher: Elsevier BV

Date: 05-2020

DOI: 10.1016/J.JARIDENV.2019.104098

A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing

Publisher: Springer Science and Business Media LLC

Date: 06-06-2022

DOI: 10.1186/S40643-022-00550-2

Abstract: Microfluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. Here, for the first time, we presented a 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator. We showed that this system can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality. The system can be multiplexed and scaled up to process large volumes of the industry. Importantly, this system is a closed system with no human intervention and is promising for current good manufacturing practices. Graphical Abstract

Incorporation of Nanoalumina Improves Mechanical Properties and Osteogenesis of Hydroxyapatite Bioceramics

Publisher: American Chemical Society (ACS)

Date: 05-03-2018

DOI: 10.1021/ACSBIOMATERIALS.7B00754

COVID-19 Spreading Prediction in a Control Room of Power Plant Using CFD Simulation

Publisher: Research Square Platform LLC

Date: 24-03-2022

DOI: 10.21203/RS.3.RS-1389314/V1

Abstract: Coughing and sneezing are the main ways of spreading coronavirus-2019 (SARS-CoV-2). Strategically critical facilities such as power plants cannot be shut down even in challenging situations like the COVID-19 outbreak. The personnel of the power plants' control room need to work together at close distances. This study presents the computational fluid dynamics (CFD) simulation results on the dispersion and transport of respiratory droplets emitted by an infected person coughs in a control room with an air ventilation system. This information would be helpful for risk assessment and for developing mitigation measures to prevent the spread of infection. The turbulent airflow in the control room is simulated using the k-ε model. The particle equation of motion included the drag, the Saffman lift, the Brownian, gravity/buoyancy, and thermophoresis forces. The simulation results showed that after 115 s, the cough droplets are dispersed in the entire room, and there is no safe (virus-free) space in the control room. Therefore, a safer design for the ventilation system is proposed by placing the ventilation air inlet and outlet registers across the control room and creating airflow patterns similar to air curtains that ided the room into three compartments.

Large-Volume Microfluidic Cell Sorting for Biomedical Applications.

Publisher: Annual Reviews

Date: 07-12-2015

DOI: 10.1146/ANNUREV-BIOENG-071114-040818

Abstract: Microfluidic cell-separation technologies have been studied for almost two decades, but the limited throughput has restricted their impact and range of application. Recent advances in microfluidics enable high-throughput cell sorting and separation, and this has led to various novel diagnostic and therapeutic applications that previously had been impossible to implement using microfluidics technologies. In this review, we focus on recent progress made in engineering large-volume microfluidic cell-sorting methods and the new applications enabled by them.

Biosensors and nanobiosensors for rapid detection of autoimmune diseases: a review.

Publisher: Springer Science and Business Media LLC

Date: 23-11-2019

DOI: 10.1007/S00604-019-3844-4

Abstract: This review (with 77 refs.) describes the progress that has been made in biosensors for the detection of autoimmune diseases, mainly via detection of autoantibodies. In addition, specific proteins, cytokines and ions have also been introduced as promising diagnostic biomarkers. Following an introduction into the various kinds of autoimmune diseases, we first discuss the state of the art in respective electrochemical biosensors and nanobiosensors (with subsections on erometric, impedimetric, voltammetric and photoelectrochemical methods). The next large chapter covers optical methods (with subsections on electrochemiluminescence, fluorescence and surface plasmon resonance). We then make a critical comparison between commercially available kits used for detection of autoimmune diseases with the established biosensors. Several Tables are also presented that give an overview on the wealth of methods and nanomaterials. Finally, in the conclusion part, we summarize the current status, addresse present issues, and give an outlook on potential future opportunities. Graphical abstractSchematic representation of various developed optical and electrochemical biosensors and nanobiosensors for rapid detection of autoimmune diseases nanobiosensors for rapid detection of autoimmune diseases which could significantly prevent irreversable tissue damages and increse the quality of life in these patients.

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

Publisher: Frontiers Media SA

Date: 08-03-2023

DOI: 10.3389/FIMMU.2023.1090416

Abstract: The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases’ vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs’ unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.

An Accurate PSO-GA Based Neural Network to Model Growth of Carbon Nanotubes

Publisher: Hindawi Limited

Date: 2017

DOI: 10.1155/2017/9702384

Abstract: By combining particle swarm optimization (PSO) and genetic algorithms (GA) this paper offers an innovative algorithm to train artificial neural networks (ANNs) for the purpose of calculating the experimental growth parameters of CNTs. The paper explores experimentally obtaining data to train ANNs, as a method to reduce simulation time while ensuring the precision of formal physics models. The results are compared with conventional particle swarm optimization based neural network (CPSONN) and Levenberg–Marquardt (LM) techniques. The results show that PSOGANN can be successfully utilized for modeling the experimental parameters that are critical for the growth of CNTs.

Background-free fibre optic Brillouin probe for remote mapping of micromechanics

Publisher: Optica Publishing Group

Date: 26-10-2020

DOI: 10.1364/BOE.404535

Abstract: Brillouin imaging (BI) has become a valuable tool for micromechanical material characterisation, thanks to extensive progress in instrumentation in the last few decades. This powerful technique is contactless and label-free, thus making it especially suitable for biomedical applications. Nonetheless, to fully harness the non-contact and non-destructive nature of BI, transformational changes in instrumentation are still needed to extend the technology’s utility into the domain of in vivo and in situ operation, which we foresee to be particularly crucial for wide spread usage of BI, e.g. in medical diagnostics and pathology screening. This work addresses this challenge by presenting the first demonstration of a fibre-optic Brillouin probe, capable of mapping the micromechanical properties of a tissue-mimicking phantom. This is achieved through combination of miniaturised optical design, advanced hollow-core fibre fabrication and high-resolution 3D printing. Our prototype probe is compact, background-free and possesses the highest collection efficiency to date, thus providing the foundation of a fibre-based Brillouin device for remote, in situ measurements in challenging and otherwise difficult-to-reach environments in biomedical, material science and industrial applications.

Capillary-assisted microfluidic biosensing platform captures single cell secretion dynamics in nanoliter compartments

Publisher: Elsevier BV

Date: 05-2020

DOI: 10.1016/J.BIOS.2020.112113

IEEE Access Special Section Editorial: Wearable and Implantable Devices and Systems

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 2019

DOI: 10.1109/ACCESS.2019.2942728

Surface modification of polypropylene membrane for the removal of iodine using polydopamine chemistry

Publisher: Elsevier BV

Date: 06-2020

DOI: 10.1016/J.CHEMOSPHERE.2020.126079

Engineering biomimetic hair bundle sensors for underwater sensing applications

Publisher: Author(s)

Date: 2018

DOI: 10.1063/1.5038533

Short term ex-vivo expansion of circulating head and neck tumour cells

Publisher: Impact Journals, LLC

Date: 09-08-2016

DOI: 10.18632/ONCOTARGET.11159

The role of 3D printing in the fight against COVID-19 outbreak

Publisher: Future Medicine Ltd

Date: 03-2021

DOI: 10.2217/3DP-2020-0028

Abstract: Along with the COVID-19 pandemic, urgent needs for medical and specialized products, especially personal protective equipment, has been overwhelming. The conventional production line of medical devices has been challenged by excessive global demand, and the need for an easy, low-cost and rapid fabrication method is felt more than ever. In a scramble to address this shortfall, manufacturers referred to additive manufacturing or 3D printing to fill the gap and increase the production line of medical devices. Various previously/conventionally fabricated designs have been modified and redesigned to suit the 3D printing requirement to fight against COVID-19. In this perspective, various designs accommodated for the current worldwide outbreak of COVID-19 are discussed and how 3D printing could help the global community against the current and future conditions has been explored.

The Isolation and Characterization of Circulating Tumor Cells from Head and Neck Cancer Patient Blood Samples Using Spiral Microfluidic Technology

Publisher: Springer New York

Date: 2019

DOI: 10.1007/978-1-4939-9769-5_8

Abstract: Metastasis is responsible for 90% of cancer-related deaths. The study of circulating tumor cells (CTCs) enables the study of the units of disease responsible for the process of metastasis. While the biology of the primary tissue is relatively known, little is understood about the cells en route to distant sites. Here we describe the isolation of CTCs using the spiral microfluidic technology for the efficient sorting of CTCs from head and neck cancer (HNC) patient blood s les. Furthermore, the molecular characterization of CTCs can aid in stratifying patients for targeted therapy such as immunotherapy, which is having a profound impact in the treatment of metastatic HNC.

Thermoset polyester-based superhydrophobic microchannels for nanofluid heat transfer applications

Publisher: SPIE

Date: 22-12-2015

DOI: 10.1117/12.2202524

Advances in MEMS and Microfluidics‐Based Energy Harvesting Technologies

Publisher: Wiley

Date: 09-02-2022

DOI: 10.1002/ADMT.202101347

Abstract: Energy harvesting from mechanical vibrations, thermal gradients, electromagnetic radiations, and solar radiations has experienced rapid progress in recent times not only to develop an alternative power source that can replace conventional batteries to energize portable and personal electronics smartly but also to achieve sustainable self‐sufficient micro/nanosystems. Utilizing micro‐electromechanical system (MEMS) and microfluidics technologies through selective designs and fabrications effectively, those energy harvesters can be considerably downsized while ensuring a stable, portable, and consistent power supply. Although ambient energy sources such as solar radiation are harvested for decades, recent developments have enabled ambient vibrations, electromagnetic radiation, and heat to be harvested wirelessly, independently, and sustainably. Developments in the field of microfluidics have also led to the design and fabrication of novel energy harvesting devices. This paper reviews the recent advancements in energy harvesting technologies such as piezoelectric, electromagnetic, electrostatic, thermoelectric, radio frequency, and solar to drive self‐powered portable electronics. Moreover, the potential application of MEMS and microfluidics as well as MEMS‐based structures and fabrication techniques for energy harvesting are summarized and presented. Finally, a few crucial challenges affecting the performance of energy harvesters are addressed.

Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy

Publisher: Impact Journals, LLC

Date: 06-05-2015

DOI: 10.18632/ONCOTARGET.3903

Abstract: Circulating tumor cells (CTCs) are considered as surrogate markers for prognosticating and evaluating patient treatment responses. Here, 226 blood s les from 92 patients with breast cancer, including patients with newly diagnosed or metastatic refractory cancer, and 16 blood s les from healthy subjects were cultured in laser-ablated microwells. Clusters containing an increasing number of cytokeratin-positive (CK+) cells appeared after 2 weeks, while most blood cells disappeared with time. Cultures were heterogeneous and exhibited two distinct sub-populations of cells: 'Small' (≤ 25 μm high nuclear/cytoplasmic ratio CD45-) cells, comprising CTCs, and 'Large' (> 25 μm low nuclear/cytoplasmic ratio CD68+ or CD56+) cells, corresponding to macrophage and natural killer-like cells. The Small cell fraction also showed copy number increases in six target genes (FGFR1, Myc, CCND1, HER2, TOP2A and ZNF217) associated with breast cancer. These expanded CTCs exhibited different proportions of epithelial-mesenchymal phenotypes and were transferable for further expansion as spheroids in serum-free suspension or 3D cultures. Cluster formation was affected by the presence and duration of systemic therapy, and its persistence may reflect therapeutic resistance. This novel and advanced method estimates CTC clonal heterogeneity and can predict, within a relatively short time frame, patient responses to therapy.

Development of a fiber-based membraneless hydrogen peroxide fuel cell

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C7RA08333E

Abstract: Polyvinylidene fluoride (PVDF) electrospun nano-fiber is suggested as the substrate material for developing biocompatible membraneless hydrogen peroxide fuel cells.

Simple-to-Operate Approach for Single Cell Analysis Using a Hydrophobic Surface and Nanosized Droplets.

Publisher: American Chemical Society (ACS)

Date: 03-03-2021

DOI: 10.1021/ACS.ANALCHEM.0C05026

A collective route to head and neck cancer metastasis

Publisher: Springer Science and Business Media LLC

Date: 15-01-2018

DOI: 10.1038/S41598-017-19117-9

Abstract: Distant metastasis (DM) from head and neck cancers (HNC) portends a poor patient prognosis. Despite its important biological role, little is known about the cells which seed these DM. Circulating tumour cells (CTCs) represent a transient cancer cell population, which circulate in HNC patients’ peripheral blood and seed at distant sites. Capture and analysis of CTCs offers insights into tumour metastasis and can facilitate treatment strategies. Whilst the data on singular CTCs have shown clinical significance, the role of CTC clusters in metastasis remains limited. In this pilot study, we assessed 60 treatment naïve HNC patients for CTCs with disease ranging from early to advanced stages, for CTC clusters utilizing spiral CTC enrichment technology. Single CTCs were isolated in 18/60–30% (Ranging from Stage I-IV), CTC clusters in 15/60–25% (exclusively Stage IV) with 3/15–20% of CTC clusters also containing leukocytes. The presence of CTC clusters associated with the development of distant metastatic disease( P = 0.0313). This study demonstrates that CTC clusters are found in locally advanced patients, and this may be an important prognostic marker. In vivo and in vitro studies are warranted to determine the role of these CTC clusters, in particular, whether leukocyte involvement in CTC clusters has clinical relevance.

Isolation and retrieval of circulating tumor cells using centrifugal forces

Publisher: Springer Science and Business Media LLC

Date: 12-02-2013

DOI: 10.1038/SREP01259

Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems.

Publisher: MDPI AG

Date: 08-03-2022

DOI: 10.3390/PHARMACEUTICS14030586

Abstract: Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists’ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.

New insights into the physics of inertial microfluidics in curved microchannels. II. Adding an additive rule to understand complex cross-sections

Publisher: AIP Publishing

Date: 05-2019

DOI: 10.1063/1.5109012

Abstract: Curved microchannels allow controllable microparticle focusing, but a full understanding of particle behavior has been limited—even for simple rectangular and trapezoidal shapes. At present, most microfluidic particle separation literature is dedicated to adding “internal” complexity (via sheath flow or obstructions) to relatively simple cross-sectional channel shapes. We propose that, with sufficient understanding of particle behavior, an equally viable pathway for microparticle focusing could utilize complex “external” cross-sectional shapes. By investigating three novel, complex spiral microchannels, we have found that it is possible to passively focus (6, 10, and 13 μm) microparticles in the middle of a convex channel. Also, we found that in concave and jagged channel designs, it is possible to create multiple, tight focusing bands. In addition to these performance benefits, we report an “additive rule” herein, which states that complex channels can be considered as multiple, independent, simple cross-sectional shapes. We show with experimental and numerical analysis that this new additive rule can accurately predict particle behavior in complex cross-sectional shaped channels and that it can help to extract general inertial focusing tendencies for suspended particles in curved channels. Overall, this work provides simple, yet reliable, guidelines for the design of advanced curved microchannel cross sections.

Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products

Publisher: Elsevier BV

Date: 10-2018

DOI: 10.1016/J.BIOMATERIALS.2018.07.016

Abstract: Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells play pivotal roles in cell-based therapies. Over the past decades, various methods for expansion and differentiation of stem cells have been developed to satisfy the burgeoning clinical demands. One of the most widely endorsed technologies for producing large cell quantities is using microcarriers (MCs) in bioreactor culture systems. In this review, we focus on microcarriers properties that can manipulate the expansion and fate of stem cells. Here, we provide an overview of commercially available MCs and focus on novel stimulus responsive MCs controlled by temperature, pH and field changes. Different features of MCs including composition, surface coating, morphology, geometry/size, surface functionalization, charge and mechanical properties, and their cellular effects are also highlighted. We then conclude with current challenges and outlook on this promising technology.

Fabrication of multi-layer polymeric micro-sieve having narrow slot pores with conventional ultraviolet-lithography and micro-fabrication techniques.

Publisher: AIP Publishing

Date: 09-2011

DOI: 10.1063/1.3637630

Abstract: Fast detection of waterborne pathogens is important for securing the hygiene of drinking water. Detection of pathogens in water at low concentrations and minute quantities demands rapid and efficient enrichment methods in order to improve the signal-to-noise ratio of bio-sensors. We propose and demonstrate a low cost and rapid method to fabricate a multi-layer polymeric micro-sieve using conventional lithography techniques. The micro-fabricated micro-sieves are made of several layers of SU-8 photoresist using multiple coating and exposure steps and a single developing process. The obtained micro-sieves have good mechanical properties, smooth surfaces, high porosity (≈40%), and narrow pore size distribution (coefficient of variation & 3.33%). S le loading and back-flushing using the multi-layer micro-sieve resulted in more than 90% recovery of pathogens, which showed improved performance than current commercial filters.

Zigzag microchannel for rigid inertial separation and enrichment (Z-RISE) of cells and particles.

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2LC00290F

Abstract: Separation and enrichment of target cells prior to downstream analyses is an essential pre-treatment step in many biomedical and clinical assays. Separation techniques utilizing simple, cost-effective, and user-friendly devices are highly desirable, both in the lab and at the point of need. Passive microfluidic approaches, especially inertial microfluidics, fit this brief perfectly and are highly desired. Using an optimized additive manufacturing technique, we developed a zigzag microchannel for rigid inertial separation and enrichment, hereafter referred to as Z-RISE. We empirically showed that the Z-RISE device outperforms equivalent devices based on curvilinear (sinusoidal), asymmetric curvilinear, zigzag with round corners, or square-wave formats and modelled this behavior to gain a better understanding of the physics underpinning the improved focusing and separation performance. The comparison between rigid and soft zigzag microchannels reveals that channel rigidity significantly affects and enhances the focusing performance of the microchannel. Compared to other serpentine microchannels, zigzag microfluidics demonstrates superior separation and purity efficiency due to the sudden channel cross-section expansion at the corners. Within Z-RISE, particles are aligned in either double-side or single-line focusing positions. The transition of particles from a double-focusing line to a single focusing line introduced a new phenomenon referred to as the plus focusing position. We experimentally demonstrated that Z-RISE could enrich leukocytes and their subtypes from diluted and RBC lysed blood while depleting dead cells, debris, and RBCs. Z-RISE was also shown to yield outstanding particle or cell concentration with a concentration efficiency of more than 99.99%. Our data support the great potential of Z-RISE for applications that involve particle and cell manipulations and pave the way for commercialization perspective in the near future.

Advances in microfluidics in combating infectious diseases.

Publisher: Elsevier BV

Date: 07-2016

DOI: 10.1016/J.BIOTECHADV.2016.02.002

Fabrication and characterization of a microporous polymeric micro-filter for isolation of Cryptosporidium parvum oocysts

Publisher: IOP Publishing

Date: 02-2011

DOI: 10.1088/0960-1317/21/3/035002

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.CANLET.2018.03.013

Abstract: The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.

Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods

Publisher: Springer Science and Business Media LLC

Date: 28-03-2023

DOI: 10.1038/S41378-023-00501-7

Abstract: Sperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen ( n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.

Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model

Publisher: Wiley

Date: 09-11-2021

DOI: 10.1002/BIT.27612

Advanced models for respiratory disease and drug studies

Publisher: Wiley

Date: 29-04-2023

DOI: 10.1002/MED.21956

Abstract: The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID‐19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung‐on‐a‐chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.

Advances in TEER measurements of biological barriers in microphysiological systems.

Publisher: Elsevier BV

Date: 08-2023

DOI: 10.1016/J.BIOS.2023.115355

Characterizing terahertz channels for monitoring human lungs with wireless nanosensor networks

Publisher: Elsevier BV

Date: 09-2016

DOI: 10.1016/J.NANCOM.2016.09.001

The role of vitamin D in the age of COVID‐19: A systematic review and meta‐analysis

Publisher: Hindawi Limited

Date: 06-08-2021

DOI: 10.1111/IJCP.14675

Diagnostic value of serum HER2 levels in breast cancer: a systematic review and meta-analysis.

Publisher: Springer Science and Business Media LLC

Date: 31-10-2020

DOI: 10.1186/S12885-020-07545-2

Abstract: Measurement of serum human epidermal growth factor receptor-2 (HER-2/ neu ) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods. We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82–65.28), but reasonable specificity of 79.27 (95%CI 73.02–85.51), accuracy of 72.06 (95%CI 67.04–77.08) and AUC of 0.79 (95%CI 0.66–0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16–68.20), NPV (NPV: 76.93, 95%CI 69.56–84.31), PLR (PLR: 2.10, 95%CI 1.69–2.50) and NLR (NLR: 0.58, 95%CI 0.44–0.71). Our findings revealed that although serum HER-2 levels showed low se nsitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends

Publisher: MDPI AG

Date: 31-12-2021

DOI: 10.3390/BIOS12010020

Abstract: Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.

Obstacle-free planar hybrid micromixer with low pressure drop

Publisher: Springer Science and Business Media LLC

Date: 15-07-2020

DOI: 10.1007/S10404-020-02367-X

INERTIAL-BASED MICROCARRIER-CELL RETENTION IN BIOPROCESSING

Publisher: Elsevier BV

Date: 05-2019

DOI: 10.1016/J.JCYT.2019.04.015

Jetting microfluidics with size-sorting capability for single-cell protease detection

Publisher: Elsevier BV

Date: 04-2015

DOI: 10.1016/J.BIOS.2014.11.001

Abstract: Activated proteases such as matrix metalloproteinases (MMPs) secreted from cancer cells can degrade the extracellular matrix (ECM) and contribute to tumour formation and metastasis. Measuring MMP activity in in idual cancer cells can provide important insights on cancer cell heterogeneity and disease progression. Here, we present a microfluidic platform combining a droplet jetting generator and a deterministic lateral displacement (DLD) size-sorting channel that is capable of encapsulating in idual cancer cells inside picoliter droplets effectively. Droplet jetting with cell-triggered Rayleigh-Plateau instability was employed which produced large droplets capable of cell encapsulation (diameter, ~25µm) and small empty droplets (diameter, ~14µm), which were then size-separated using a DLD size-sorting channel to enrich the single-cell encapsulated droplets (~78%), regardless of the cell density of input s le solutions. The droplets containing encapsulated cancer cells were collected in an observation chamber to determine the kinetic profiles of MMP secretion and the inhibitory response in the presence of the drug doxycycline at the single-cell level to reveal their heterogeneous MMPs secretion activities.

3D Printing of Inertial Microfluidic Devices.

Publisher: Springer Science and Business Media LLC

Date: 03-04-2020

DOI: 10.1038/S41598-020-62569-9

Abstract: Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.

New insights into the physics of inertial microfluidics in curved microchannels. I. Relaxing the fixed inflection point assumption

Publisher: AIP Publishing

Date: 05-2019

DOI: 10.1063/1.5109004

Abstract: Inertial microfluidics represents a powerful new tool for accurately positioning cells and microparticles within fluids for a variety of biomedical, clinical, and industrial applications. In spite of enormous advancements in the science and design of these devices, particularly in curved microfluidic channels, contradictory experimental results have confounded researchers and limited progress. Thus, at present, a complete theory which describes the underlying physics is lacking. We propose that this bottleneck is due to one simple mistaken assumption—the locations of inflection points of the Dean velocity profile in curved microchannels are not fixed, but can actually shift with the flow rate. Herein, we propose that the dynamic distance (δ) between the real equilibrium positions and their nearest inflection points can clearly explain several (previously) unexplained phenomena in inertial microfluidic systems. More interestingly, we found that this parameter, δ, is a function of several geometric and operational parameters, all of which are investigated (in detail) here with a series of experiments and simulations of different spiral microchannels. This key piece of understanding is expected to open the door for researchers to develop new and more effective inertial microfluidic designs.

Particle movement and fluid behavior visualization using an optically transparent 3D-printed micro-hydrocyclone

Publisher: AIP Publishing

Date: 11-2020

DOI: 10.1063/5.0025391

An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells

Publisher: Royal Society of Chemistry (RSC)

Date: 2014

DOI: 10.1039/C4AN00355A

Abstract: We demonstrate the high-throughput and high-resolution separation of rare circulating tumor cells (CTCs) from blood using a multiplexed spiral microfluidic device.

Microfluidics facilitating the use of small extracellular vesicles in innovative approaches to male infertility.

Publisher: Springer Science and Business Media LLC

Date: 08-11-2023

DOI: 10.1038/S41585-022-00660-8

Abstract: Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic s les with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.

Strategies for elevating hematopoietic stem cells expansion and engraftment capacity

Publisher: Elsevier BV

Date: 09-2019

DOI: 10.1016/J.LFS.2019.116598

Abstract: Hematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genetic defects such as thalassemia, sickle cell anemia, autoimmune disease, and certain solid cancers. Ex vivo proliferation of these cells prior to transplantation has been proposed as a potential solution against limited number of stem cells. In such culture process, MSCs have also been shown to exhibit high capacity for secretion of soluble mediators contributing to the principle biological and therapeutic activities of HSCs. In addition, endothelial cells have been introduced to bridge the blood and sub tissues in the bone marrow, as well as, HSCs regeneration induction and survival. Cell culture in the laboratory environment requires cell growth strict control to protect against contamination, symmetrical cell ision and optimal conditions for maximum yield. In this regard, microfluidic systems provide culture and analysis capabilities in micro volume scales. Moreover, two-dimensional cultures cannot fully demonstrate extracellular matrix found in different tissues and organs as an abstract representation of three dimensional cell structure. Microfluidic systems can also strongly describe the effects of physical factors such as temperature and pressure on cell behavior.

Reliability analysis of time-varying wireless nanoscale sensor networks

Publisher: IEEE

Date: 07-2015

DOI: 10.1109/NANO.2015.7388697

HIGHLY MULTIPLEXED DIGITAL SPATIAL PROFILING OF THE TUMOR MICROENVIRONMENT OF NON-SMALL-CELL LUNG CANCER (NSCLC)

Publisher: BMJ Publishing Group Ltd

Date: 11-2020

DOI: 10.1136/JITC-2020-SITC2020.0043

The effects of baffle configuration and number on inertial mixing in a curved serpentine micromixer: Experimental and numerical study

Publisher: Elsevier BV

Date: 04-2021

DOI: 10.1016/J.CHERD.2021.02.028

Microfluidics for fast and frugal diagnosis of malaria, sepsis, and HIV/AIDS

Publisher: Springer International Publishing

Date: 2018

DOI: 10.1007/978-3-319-66647-1_4

Microfluidic Platforms for Cell Sorting

Publisher: Wiley

Date: 29-03-2022

DOI: 10.1002/9781119740117.CH18

Nutraceuticals and COVID‐19: A mechanistic approach toward attenuating the disease complications

Publisher: Hindawi Limited

Date: 14-10-2022

DOI: 10.1111/JFBC.14445

Abstract: Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19.

Recent Advances in Chronotherapy Targeting Respiratory Diseases

Publisher: MDPI AG

Date: 25-11-2021

DOI: 10.3390/PHARMACEUTICS13122008

Abstract: Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep–wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an in idual’s circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.

The Effects of COVID-19 on the Placenta During Pregnancy.

Publisher: Frontiers Media SA

Date: 15-09-2021

DOI: 10.3389/FIMMU.2021.743022

Abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.

A 3D-printed mini-hydrocyclone for high throughput particle separation: Application to primary harvesting of microalgae

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C7LC00294G

Abstract: 3D-printed hydrocyclones are low-cost microdevices which be part of a library of standardized active and passive microfluidic components, suitable for particle–liquid separation.

A Comprehensive Review on Intracellular Delivery.

Publisher: Wiley

Date: 16-02-2021

DOI: 10.1002/ADMA.202005363

Liquid biopsy in diagnosis and prognosis of non-metastatic prostate cancer

Publisher: MDPI AG

Date: 02-12-2022

DOI: 10.3390/BIOMEDICINES10123115

Abstract: Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, erse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.

Isoporous micro/nanoengineered membranes.

Publisher: American Chemical Society (ACS)

Date: 11-03-2013

DOI: 10.1021/NN305616K

Abstract: Isoporous membranes are versatile structures with numerous potential and realized applications in various fields of science such as micro/nanofiltration, cell separation and harvesting, controlled drug delivery, optics, gas separation, and chromatography. Recent advances in micro/nanofabrication techniques and material synthesis provide novel methods toward controlling the detailed microstructure of membrane materials, allowing fabrication of membranes with well-defined pore size and shape. This review summarizes the current state-of-the-art for isoporous membrane fabrication using different techniques, including microfabrication, anodization, and advanced material synthesis. Various applications of isoporous membranes, such as protein filtration, pathogen isolation, cell harvesting, biosensing, and drug delivery, are also presented.

Advances of microfluidic technology in reproductive biology.

Publisher: Elsevier BV

Date: 2021

DOI: 10.1016/J.LFS.2020.118767

Circulating tumor cell clusters: Insights into tumour dissemination and metastasis.

Publisher: Informa UK Limited

Date: 11-2020

DOI: 10.1080/14737159.2020.1846523

Single-cell profiling approaches to probing tumor heterogeneity.

Publisher: Wiley

Date: 16-02-2016

DOI: 10.1002/IJC.30006

Abstract: Tumor heterogeneity is a major hindrance in cancer classification, diagnosis and treatment. Recent technological advances have begun to reveal the true extent of its heterogeneity. Single-cell analysis (SCA) is emerging as an important approach to detect variations in morphology, genetic or proteomic expression. In this review, we revisit the issue of inter- and intra-tumor heterogeneity, and list various modes of SCA techniques (cell-based, nucleic acid-based, protein-based, metabolite-based and lipid-based) presently used for cancer characterization. We further discuss the advantages of SCA over pooled cell analysis, as well as the limitations of conventional techniques. Emerging trends, such as high-throughput sequencing, are also mentioned as improved means for cancer profiling. Collectively, these applications have the potential for breakthroughs in cancer treatment.

Recent advances in lung-on-a-chip models.

Publisher: Elsevier BV

Date: 09-2022

DOI: 10.1016/J.DRUDIS.2022.06.004

Abstract: With the global burden of respiratory diseases, rapid identification of the best therapeutic measures to combat these diseases is essential. Animal models and 2D cell culture models do not replicate the findings observed in vivo. To gain deeper insight into lung pathology and physiology, 3D and advanced lung-on-a-chip models have been developed recently. Lung-on-a-chip models more accurately simulate the lung's microenvironment and functions in vivo, resulting in more-accurate assessments of drug safety and effectiveness. This review discusses the transition from 2D to 3D models and the recent advances in lung-on-a-chip platforms, their implementation and the numerous challenges faced. Finally, a general overview of this platform and its potential applications in respiratory disease research and drug discovery is highlighted.

Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics.

Publisher: Springer Science and Business Media LLC

Date: 17-12-2016

DOI: 10.1038/NPROT.2016.003

Abstract: Circulating tumor cells (CTCs) are rare cancer cells that are shed from primary or metastatic tumors into the peripheral blood circulation. Phenotypic and genetic characterization of these rare cells can provide important information to guide cancer staging and treatment, and thus further research into their characteristics and properties is an area of considerable interest. In this protocol, we describe detailed procedures for the production and use of a label-free spiral microfluidic device to allow size-based isolation of viable CTCs using hydrodynamic forces that are present in curvilinear microchannels. This spiral system enables us to achieve ≥ 85% recovery of spiked cells across multiple cancer cell lines and 99.99% depletion of white blood cells in whole blood. The described spiral microfluidic devices can be produced at an extremely low cost using standard microfabrication and soft lithography techniques (2-3 d), and they can be operated using two syringe pumps for lysed blood s les (7.5 ml in 12.5 min for a three-layered multiplexed chip). The fast processing time and the ability to collect CTCs from a large patient blood volume allows this technique to be used experimentally in a broad range of potential genomic and transcriptomic applications.

The evolving landscape of predictive biomarkers in immuno‐oncology with a focus on spatial technologies

Publisher: Wiley

Date: 2020

DOI: 10.1002/CTI2.1215

Scaled‐Up Inertial Microfluidics: Retention System for Microcarrier‐Based Suspension Cultures

Publisher: Wiley

Date: 15-04-2019

DOI: 10.1002/BIOT.201800674

Abstract: Recently, particle concentration and filtration using inertial microfluidics have drawn attention as an alternative to membrane and centrifugal technologies for industrial applications, where the target particle size varies between 1 µm and 500 µm. Inevitably, the bigger particle size (>50 µm) mandates scaling up the channel cross-section or hydraulic diameter (D

Sensitive and Flexible Polymeric Strain Sensor for Accurate Human Motion Monitoring.

Publisher: MDPI AG

Date: 02-2018

DOI: 10.3390/S18020418

Advances and enabling technologies for phase-specific cell cycle synchronisation

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1LC00724F

Abstract: Schematic illustration of conventional (left) and microfluidics-based (right) phase-specific cell cycle synchronization strategies.

3D printing enables the rapid prototyping of modular microfluidic devices for particle conjugation

Publisher: Elsevier BV

Date: 09-2020

DOI: 10.1016/J.APMT.2020.100726

Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells.

Publisher: Springer Science and Business Media LLC

Date: 18-09-2023

DOI: 10.1007/S12015-023-10585-3

Front Cover Image, Volume 43, Issue 5

Publisher: Wiley

Date: 07-08-2023

DOI: 10.1002/MED.21908

Microfluidics: Rapid Softlithography Using 3D‐Printed Molds (Adv. Mater. Technol. 10/2019)

Publisher: Wiley

Date: 10-2019

DOI: 10.1002/ADMT.201970056

MEMS piezoresistive flow sensors for sleep apnea therapy

Publisher: Elsevier BV

Date: 08-2018

DOI: 10.1016/J.SNA.2018.06.038

Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness

Publisher: Public Library of Science (PLoS)

Date: 23-07-2021

DOI: 10.1371/JOURNAL.PCBI.1009193

Abstract: Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of in idual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET.

Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration

Publisher: Springer Science and Business Media LLC

Date: 03-2018

DOI: 10.1007/S10404-018-2045-5

Lung-on-a-chip: the future of respiratory disease models and pharmacological studies

Publisher: Informa UK Limited

Date: 06-01-2020

DOI: 10.1080/07388551.2019.1710458

Abstract: Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional

Membrane-less microfiltration using inertial microfluidics.

Publisher: Springer Science and Business Media LLC

Date: 08-07-2015

DOI: 10.1038/SREP11018

Abstract: Microfiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10–20 μm) and yeast (3–5 μm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes.

A Microfluidic Approach for Enrichment and Single-Cell Characterization of Circulating Tumor Cells from Peripheral Blood.

Publisher: Springer US

Date: 2023

DOI: 10.1007/978-1-0716-3271-0_9

Manipulating electrokinetic conductance of nanofluidic channel by varying inlet pH of solution

Publisher: Springer Science and Business Media LLC

Date: 03-2017

DOI: 10.1007/S10404-017-1892-9

A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal Neurons

Publisher: Springer Science and Business Media LLC

Date: 14-09-2018

DOI: 10.1007/S10571-018-0620-7

Abstract: Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system.

Emerging Standards and the Hybrid Model for Organizing Scientific Events During and After the COVID-19 Pandemic

Publisher: Cambridge University Press (CUP)

Date: 26-10-2020

DOI: 10.1017/DMP.2020.406

Abstract: Since the beginning of 2020, the coronavirus disease (COVID-19) pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, canceled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings online, advantages of which include increased inclusivity and accessibility and a reduced carbon footprint. However, emerging online technologies cannot fully replace in-person scientific events. In-person meetings are not susceptible to poor Internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies, including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system, which was neglected previously and should become a part of routine practice in the scientific community.

Clinical Applications of Circulating Tumour Cells and Circulating Tumour DNA in Non-Small Cell Lung Cancer—An Update

Publisher: Frontiers Media SA

Date: 15-03-2022

DOI: 10.3389/FONC.2022.859152

Abstract: Despite efforts to improve earlier diagnosis of non-small cell lung cancer (NSCLC), most patients present with advanced stage disease, which is often associated with poor survival outcomes with only 15% surviving for 5 years from their diagnosis. Tumour tissue biopsy is the current mainstream for cancer diagnosis and prognosis in many parts of the world. However, due to tumour heterogeneity and accessibility issues, liquid biopsy is emerging as a game changer for both cancer diagnosis and prognosis. Liquid biopsy is the analysis of tumour-derived biomarkers in body fluids, which has remarkable advantages over the use of traditional tumour biopsy. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) are two main derivatives of liquid biopsy. CTC enumeration and molecular analysis enable monitoring of cancer progression, recurrence, and treatment response earlier than traditional biopsy through a minimally invasive liquid biopsy approach. CTC-derived ex-vivo cultures are essential to understanding CTC biology and their role in metastasis, provide a means for personalized drug testing, and guide treatment selection. Just like CTCs, ctDNA provides opportunity for screening, monitoring, treatment evaluation, and disease surveillance. We present an updated review highlighting the prognostic and therapeutic significance of CTCs and ctDNA in NSCLC.

PCR-free paper-based nanobiosensing platform for visual detection of telomerase activity via gold enhancement

Publisher: Elsevier BV

Date: 05-2020

DOI: 10.1016/J.MICROC.2020.104594

Application of microfluidic technology in cancer research and therapy.

Publisher: Elsevier

Date: 2020

DOI: 10.1016/BS.ACC.2020.02.012

Combined effects of 3D bone marrow stem cell-seeded wet-electrospun poly lactic acid scaffolds on full-thickness skin wound healing

Publisher: Informa UK Limited

Date: 08-01-2018

DOI: 10.1080/00914037.2017.1393681

Isolation of Circulating Tumour Cells in Patients With Glioblastoma Using Spiral Microfluidic Technology – A Pilot Study

Publisher: Frontiers Media SA

Date: 03-06-2021

DOI: 10.3389/FONC.2021.681130

Abstract: Glioblastoma (GBM) is the most common and aggressive type of tumour arising from the central nervous system. GBM remains an incurable disease despite advancement in therapies, with overall survival of approximately 15 months. Recent literature has highlighted that GBM releases tumoural content which crosses the blood-brain barrier (BBB) and is detected in patients’ blood, such as circulating tumour cells (CTCs). CTCs carry tumour information and have shown promise as prognostic and predictive biomarkers in different cancer types. Currently, there is limited data for the clinical utility of CTCs in GBM. Here, we report the use of spiral microfluidic technology to isolate CTCs from whole blood of newly diagnosed GBM patients before and after surgery, followed by characterization for GFAP, cell-surface vimentin protein expression and EGFR lification. CTCs were found in 13 out of 20 patients (9/20 before surgery and 11/19 after surgery). Patients with CTC counts equal to 0 after surgery had a significantly longer recurrence-free survival (p=0.0370). This is the first investigation using the spiral microfluidics technology for the enrichment of CTCs from GBM patients and these results support the use of this technology to better understand the clinical value of CTCs in the management of GBM in future studies.

Giardia purification from fecal samples using rigid spiral inertial microfluidics

Publisher: AIP Publishing

Date: 2022

DOI: 10.1063/5.0069406

Abstract: Giardia is one of the most common waterborne pathogens causing around 200 × 106 diarrheal infections annually. It is of great interest to microbiological research as it is among the oldest known eukaryotic cells. Purifying Giardia from fecal s les for both research and diagnostic purposes presents one of the most difficult challenges. Traditional purification methods rely on density gradient centrifugation, membrane-based filtration, and sedimentation methods, which suffer from low recovery rates, high costs, and poor efficiency. Here, we report on the use of microfluidics to purify Giardia cysts from mouse feces. We propose a rigid spiral microfluidic device with a trapezoidal cross section to effectively separate Giardia from surrounding debris. Our characterizations reveal that the recovery rate is concentration-dependent, and our proposed device can achieve recovery rates as high as 75% with 0.75 ml/min throughput. Moreover, this device can purify Giardia from extremely turbid s les to a level where cysts are visually distinguishable with just one round of purification. This highly scalable and versatile 3D printed microfluidic device is then capable of further purifying or enhancing the recovery rate of the s les by recirculation. This device also has the potential to purify other gastrointestinal pathogens of similar size, and throughput can be significantly increased by parallelization.

Ultra-high throughput enrichment of viable circulating tumor cells

Publisher: Springer International Publishing

Date: 2014

DOI: 10.1007/978-3-319-02913-9_1

A high-flux isopore micro-fabricated membrane for effective concentration and recovering of waterborne pathogens.

Publisher: Springer Science and Business Media LLC

Date: 24-03-2012

DOI: 10.1007/S10544-012-9647-6

Abstract: A high-flux metallic micro/nano-filtration membrane has been fabricated and validated for isolation of waterborne pathogens from drinking water. Obtained membrane with smooth surface and perfectly ordered pores was achieved by a high yield and cost effective multilevel lithography and electroplating technique. The micro-fabricated membrane was also strengthened with an integrated back-support, which can withstand a high pressure during filtration. The results of microfiltration tests with model particles revealed the superior performance of the micro-fabricated filter than current commercial filters in s le throughput, recovery ratio, and reusability. This study highlighted the potential application of micro-fabricated filer in rapid filtration and recovery of C. parvum oocysts for downstream analysis.

Developing Novel Fabrication and Optimisation Strategies on Aggregation-Induced Emission Nanoprobe/Polyvinyl Alcohol Hydrogels for Bio-Applications

Publisher: MDPI AG

Date: 02-02-2022

DOI: 10.3390/MOLECULES27031002

Abstract: The current study describes a new technology, effective for readily preparing a fluorescent (FL) nanoprobe-based on hyperbranched polymer (HB) and aggregation-induced emission (AIE) fluorogen with high brightness to ultimately develop FL hydrogels. We prepared the AIE nanoprobe using a microfluidic platform to mix hyperbranched polymers (HB, generations 2, 3, and 4) with AIE (TPE-2BA) under shear stress and different rotation speeds (0–5 K RPM) and explored the FL properties of the AIE nanoprobe. Our results reveal that the use of HB generation 4 exhibits 30-times higher FL intensity compared to the AIE alone and is significantly brighter and more stable compared to those that are prepared using HB generations 3 and 2. In contrast to traditional methods, which are expensive and time-consuming and involve polymerization and post-functionalization to develop FL hyperbranched molecules, our proposed method offers a one-step method to prepare an AIE-HB nanoprobe with excellent FL characteristics. We employed the nanoprobe to fabricate fluorescent injectable bioadhesive gel and a hydrogel microchip based on polyvinyl alcohol (PVA). The addition of borax (50 mM) to the PVA + AIE nanoprobe results in the development of an injectable bioadhesive fluorescent gel with the ability to control AIEgen release for 300 min. When borax concentration increases two times (100 mM), the adhesion stress is more than two times bigger (7.1 mN/mm2) compared to that of gel alone (3.4 mN/mm2). Excellent dimensional stability and cell viability of the fluorescent microchip, along with its enhanced mechanical properties, proposes its potential applications in mechanobiology and understanding the impact of microstructure in cell studies.

A rapidly prototyped lung-on-a-chip model using 3D-printed molds

Publisher: Elsevier BV

Date: 12-2019

DOI: 10.1016/J.OOC.2020.100001

Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta

Publisher: Oxford University Press (OUP)

Date: 07-2020

DOI: 10.1093/INTBIO/ZYAA014

Abstract: Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.

Rapid and Continuous Cryopreservation of Stem Cells with a 3D Micromixer

Publisher: MDPI AG

Date: 13-09-2022

DOI: 10.3390/MI13091516

Abstract: Cryopreservation is the final step of stem cell production before the cryostorage of the product. Conventional methods of adding cryoprotecting agents (CPA) into the cells can be manual or automated with robotic arms. However, challenging issues with these methods at industrial-scale production are the insufficient mixing of cells and CPA, leading to damage of cells, discontinuous feeding, the batch-to-batch difference in products, and, occasionally, cross-contamination. Therefore, the current study proposes an alternative way to overcome the abovementioned challenges a highly efficient micromixer for low-cost, continuous, labour-free, and automated mixing of stem cells with CPA solutions. Our results show that our micromixer provides a more homogenous mixing of cells and CPA compared to the manual mixing method, while the cell properties, including surface markers, differentiation potential, proliferation, morphology, and therapeutic potential, are well preserved.

Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells

Publisher: Public Library of Science (PLoS)

Date: 07-07-2014

DOI: 10.1371/JOURNAL.PONE.0099409

Miniature auto‐perfusion bioreactor system with spiral microfluidic cell retention device

Publisher: Wiley

Date: 03-2021

DOI: 10.1002/BIT.27709

Abstract: Medium perfusion is critical in maintaining high cell concentration in cultures. The conventional membrane filtration method for medium exchange has been challenged by the fouling and clogging of the membrane filters in long‐term cultures. In this study, we present a miniature auto‐perfusion system that can be operated inside a common‐size laboratory incubator. The system is equipped with a spiral microfluidic chip for cell retention to replace conventional membrane filters, which fundamentally overcomes the clogging and fouling problem. We showed that the system supported continuous perfusion culture of Chinese hamster ovary (CHO) cells in suspension up to 14 days without cell retention chip replacement. Compared to daily manual medium change, 25% higher CHO cell concentration can be maintained at an average auto‐perfusion rate of 196 ml/day in spinner flask at 70 ml working volume (2.8 VVD). The auto‐perfusion system also resulted in better cell quality at high concentrations, in terms of higher viability, more uniform and regular morphology, and fewer aggregates. We also demonstrated the potential application of the system for culturing mesenchymal stem cells on microcarriers. This miniature auto‐perfusion system provides an excellent solution to maintain cell‐favorable conditions and high cell concentration in small‐scale cultures for research and clinical uses.

Single-cell analysis of circulating tumour cells: enabling technologies and clinical applications.

Publisher: Elsevier BV

Date: 09-2022

DOI: 10.1016/J.TIBTECH.2022.02.004

Abstract: Multimodal analysis of circulating tumour cells (CTCs) has the potential to provide remarkable insight for cancer development and metastasis. CTCs and CTC clusters investigation using single-cell analysis, enables researchers to gain crucial information on metastatic mechanisms and the genomic alterations responsible for drug resistance, empowering treatment, and management of cancer. Despite a plethora of CTC isolation technologies, careful attention to the strengths and weaknesses of each method should be considered in order to isolate these rare cells. Here, we provide an overview of cutting-edge technologies used for single-cell isolation and analysis of CTCs. Additionally, we highlight the biological features, clinical application, and the therapeutic potential of CTCs and CTC clusters using single-cell analysis platforms for cancer management.

Generation and Culture of Organotypic Breast Carcinoma Spheroids for the Study of Drug Response in a 3D Microfluidic Device.

Publisher: Springer US

Date: 2022

DOI: 10.1007/978-1-0716-2513-2_4

Abstract: Breast cancer (BC) is a leading cause of cancer death among women worldwide. To better understand and predict therapeutic response in BC patient developing a fast, low-cost, and reliable preclinical tumor from patient's tumor specimen is needed. Here, we describe the development of a preclinical model of BC through the generation and ex vivo culture of patient-derived organotypic tumor spheroids (PDOTS) in a 3D microfluidic device. Moreover, the real-time screening of conventional chemotherapy agents on cultured PDOTS is also described.

Numerical and Experimental Study of Cross-Sectional Effects on the Mixing Performance of the Spiral Microfluidics.

Publisher: MDPI AG

Date: 29-11-2021

DOI: 10.3390/MI12121470

Abstract: Mixing at the microscale is of great importance for various applications ranging from biological and chemical synthesis to drug delivery. Among the numerous types of micromixers that have been developed, planar passive spiral micromixers have gained considerable interest due to their ease of fabrication and integration into complex miniaturized systems. However, less attention has been paid to non-planar spiral micromixers with various cross-sections and the effects of these cross-sections on the total performance of the micromixer. Here, mixing performance in a spiral micromixer with different channel cross-sections is evaluated experimentally and numerically in the

Advanced bioengineering of male germ stem cells to preserve fertility.

Publisher: SAGE Publications

Date: 2021

DOI: 10.1177/20417314211060590

Abstract: In modern life, several factors such as genetics, exposure to toxins, and aging have resulted in significant levels of male infertility, estimated to be approximately 18% worldwide. In response, substantial progress has been made to improve in vitro fertilization treatments (e.g. microsurgical testicular sperm extraction (m-TESE), intra-cytoplasmic sperm injection (ICSI), and round spermatid injection (ROSI)). Mimicking the structure of testicular natural extracellular matrices (ECM) outside of the body is one clear route toward complete in vitro spermatogenesis and male fertility preservation. Here, a new wave of technological innovations is underway applying regenerative medicine strategies to cell-tissue culture on natural or synthetic scaffolds supplemented with bioactive factors. The emergence of advanced bioengineered systems suggests new hope for male fertility preservation through development of functional male germ cells. To date, few studies aimed at in vitro spermatogenesis have resulted in relevant numbers of mature gametes. However, a substantial body of knowledge on conditions that are required to maintain and mature male germ cells in vitro is now in place. This review focuses on advanced bioengineering methods such as microfluidic systems, bio-fabricated scaffolds, and 3D organ culture applied to the germline for fertility preservation through in vitro spermatogenesis.

Acetylated bovine serum albumin differentially inhibits polymerase chain reaction in microdevices

Publisher: AIP Publishing

Date: 05-2017

DOI: 10.1063/1.4983692

Abstract: Bovine serum albumin (BSA) is widely used as an additive in polymerase chain reaction (PCR)-based microfluidic devices to passivate reactors and alleviate nucleic-acid lification. BSA is available commercially in two types: either acetylated or non-acetylated. A survey of literature indicates that both types of BSA are used in PCR-based microfluidic devices. Our study results reveal that the use of acetylated BSA in PCR micro-devices leads to differential inhibition of PCR, compared to non-acetylated BSA. This result is noticed for the first time, and the differential inhibition generally goes un-noticed, as compared to complete PCR inhibition.

Correction: Outside back cover (volume 15, issue 21)

Publisher: Royal Society of Chemistry (RSC)

Date: 2015

DOI: 10.1039/C5LC90125A

Metal-organic framework-based nanomaterials for bone tissue engineering and wound healing

Publisher: Elsevier BV

Date: 03-2022

DOI: 10.1016/J.MTCHEM.2021.100670

Capturing and recovering of Cryptosporidium parvum oocysts with polymeric micro-fabricated filter

Publisher: Elsevier BV

Date: 03-2011

DOI: 10.1016/J.MEMSCI.2010.12.038

Affibody functionalized beads for the highly sensitive detection of cancer cell-derived exosomes

Publisher: MDPI AG

Date: 06-11-2021

DOI: 10.3390/IJMS222112014

Abstract: Exosomes belong to the class of extracellular vesicles of endocytic origin, which are regarded as a promising source of cancer biomarkers in liquid biopsy. As a result, an accurate, sensitive, and specific quantification of these nano-sized particles is of significant importance. Affinity-based approaches are recognized as the most valuable technique for exosome isolation and characterization. Indeed, Affibody biomolecules are a type of protein scaffold engineered with small size and enjoy the features of high thermal stability, affinity, and specificity. While the utilization of antibodies, aptamers, and other biologically active substances for exosome detection has been reported widely, there are no reports describing Affibody molecules’ usage for exosome detection. In this study, for the first time, we have proposed a novel strategy of using Affibody functionalized microbeads (AffiBeads) for exosome detection with a high degree of efficiency. As a proof-of-concept, anti-EGFR-AffiBeads were fabricated and applied to capture and detect human lung A549 cancer cell-derived EGFR-positive exosomes using flow cytometry and fluorescent microscopy. Moreover, the capture efficiency of the AffiBeads were compared with its counterpart antibody. Our results showed that the Affibody probe had a detection limit of 15.6 ng exosomes per mL (~12 exosomes per AffiBead). The approach proposed in the current study can be used for sensitive detection of low expression level markers on tumor-derived exosomes, providing a basis for early-stage cancer diagnosis.

ImmunoInertial microfluidics: A novel strategy for isolation of small EV subpopulations

Publisher: Elsevier BV

Date: 02-2023

DOI: 10.1016/J.APMT.2022.101730

Twisted architecture for enhancement of passive micromixing in a wide range of Reynolds numbers

Publisher: Elsevier BV

Date: 03-2021

DOI: 10.1016/J.CEP.2020.108251

Numerical and experimental study of capillary-driven flow of PCR solution in hybrid hydrophobic microfluidic networks.

Publisher: Springer Science and Business Media LLC

Date: 18-07-2016

DOI: 10.1007/S10544-016-0099-2

Abstract: Capillary-driven microfluidics is essential for development of point-of-care diagnostic micro-devices. Polymerase chain reaction (PCR)-based micro-devices are widely developed and used in such point-of-care settings. It is imperative to characterize the fluid parameters of PCR solution for designing efficient capillary-driven microfluidic networks. Generally, for numeric modelling, the fluid parameters of PCR solution are approximated to that of water. This procedure leads to inaccurate results, which are discrepant to experimental data. This paper describes mathematical modeling and experimental validation of capillary-driven flow inside Poly-(dimethyl) siloxane (PDMS)-glass hybrid micro-channels. Using experimentally measured PCR fluid parameters, the capillary meniscus displacement in PDMS-glass microfluidic ladder network is simulated using computational fluid dynamic (CFD), and experimentally verified to match with the simulated data.

Spermatogenesis induction of spermatogonial stem cells using nanofibrous poly(l-lactic acid)/multi-walled carbon nanotube scaffolds and naringenin

Publisher: Wiley

Date: 08-2019

DOI: 10.1002/PAT.4733

Rapid Softlithography Using 3D-Printed Molds

Publisher: Wiley

Date: 12-08-2019

DOI: 10.1002/ADMT.201900425

Kinetic and thermodynamic study of c-Met interaction with single chain fragment variable (scFv) antibodies using phage based surface plasmon resonance

Publisher: Elsevier BV

Date: 07-2020

DOI: 10.1016/J.EJPS.2020.105362

High-Throughput Particle Concentration Using Complex Cross-Section Microchannels

Publisher: MDPI AG

Date: 22-04-2020

DOI: 10.3390/MI11040440

Abstract: High throughput particle/cell concentration is crucial for a wide variety of biomedical, clinical, and environmental applications. In this work, we have proposed a passive spiral microfluidic concentrator with a complex cross-sectional shape, i.e., a combination of rectangle and trapezoid, for high separation efficiency and a confinement ratio less than 0.07. Particle focusing in our microfluidic system was observed in a single, tight focusing line, in which higher particle concentration is possible, as compared with simple rectangular or trapezoidal cross-sections with similar flow area. The sharper focusing stems from the confinement of Dean vortices in the trapezoidal region of the complex cross-section. To quantify this effect, we introduce a new parameter, complex focusing number or CFN, which is indicative of the enhancement of inertial focusing of particles in these channels. Three spiral microchannels with various widths of 400 µm, 500 µm, and 600 µm, with the corresponding CFNs of 4.3, 4.5, and 6, respectively, were used. The device with the total width of 600 µm was shown to have a separation efficiency of ~98%, and by recirculating, the output concentration of the s le was 500 times higher than the initial input. Finally, the investigation of results showed that the magnitude of CFN relies entirely on the microchannel geometry, and it is independent of the overall width of the channel cross-section. We envision that this concept of particle focusing through complex cross-sections will prove useful in paving the way towards more efficient inertial microfluidic devices.

A hybrid micromixer with planar mixing units

Publisher: Royal Society of Chemistry (RSC)

Date: 2018

DOI: 10.1039/C8RA05763J

Abstract: Taguchi-optimized “hybrid micromixer” has been proposed which can be utilized in a wide range of chemical and biological applications.

Abstract 3384: Characterization of the tumor microenvironment and liquid biopsy in head and neck and non-small cell lung cancer

Publisher: American Association for Cancer Research (AACR)

Date: 15-08-2020

DOI: 10.1158/1538-7445.AM2020-3384

Abstract: Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an in idual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=350) and lung cancer (n=150) patients were recruited to investigate the prognostic role of CTCs. In parallel, a subset of HNC tumors were profiled using the NanoString GeoMx Digital Spatial Profiling (DSP) technology using a 44-plex antibody cocktail. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, Spiral, Straight and novel microfluidic chip technology) using matched patient s les which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR- lification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (Hazard ratio [HR]: 4.946 95% [CI]:1.571-15.57 P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159 95% [CI]:1.011-26.33 P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient's body and exome sequencing of CTCs cultures confirmed the presence of mutational signatures consistent with The Cancer Genome Atlas (TCGA). Spatial characterization of the tumor microenvironment revealed immune subsets predictive of outcome to immunotherapy. Comprehensive characterization of the tumor microenvironment and liquid biopsy allows for the recapitulation of the molecular ersity present within the tumor, understanding of the disease progression and testing of therapies. Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Brett Hughes, Majid Warkiani, Ian Vela, Jean-Paul Thiery, Ken O'Byrne, Chamindie Punyadeera. Characterization of the tumor microenvironment and liquid biopsy in head and neck and non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR Cancer Res 2020 (16 Suppl):Abstract nr 3384.

Circulating tumour cell RNA characterisation from colorectal cancer patient blood after inertial microfluidic enrichment

Publisher: Elsevier BV

Date: 2019

DOI: 10.1016/J.MEX.2019.06.012

Transparent Surfaces Inspired by Nature

Publisher: Wiley

Date: 09-05-2018

DOI: 10.1002/ADOM.201800091

An easy-to-operate method for single-cell isolation and retrieval using a microfluidic static droplet array.

Publisher: Springer Science and Business Media LLC

Date: 06-07-2021

DOI: 10.1007/S00604-021-04897-9

Abstract: In-depth study of cellular heterogeneity of rare cells (e.g. circulating tumour cells (CTCs) and circulating foetal cells (CFCs)) is greatly needed in disease management but has never been completely explored due to the current technological limitations. We have developed a retrieval method for single-cell detection using a static droplet array (SDA) device through liquid segmentation with almost no s le loss. We explored the potential of using SDA for low s le input and retrieving the cells of interest using everyday laboratory equipment for downstream molecular analysis. This single-cell isolation and retrieval method is low-cost, rapid and provides a solution to the remaining challenge for single rare cell detection. The entire process takes less than 15 min, is easy to fabricate and allows for on-chip analysis of cells in nanolitre droplets and retrieval of desired droplets. To validate the applicability of our device and method, we mimicked detection of single CTCs by isolating and retrieving single cells and perform real-time PCR on their mRNA contents.

Enrichment of circulating head and neck tumour cells using spiral microfluidic technology

Publisher: Springer Science and Business Media LLC

Date: 15-02-2017

DOI: 10.1038/SREP42517

Abstract: Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC.

Design and Analysis of a Wireless Nanosensor Network for Monitoring Human Lung Cells

Publisher: ICST

Date: 2015

DOI: 10.4108/EAI.28-9-2015.2261516

University Of Technology Sydney

Location: Australia

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Massachusetts Institute Of Technology

Location: United States of America

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University Of New South Wales

Location: Australia

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Nanyang Technological University

Location: Singapore

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Discovery Projects - Grant ID: DP200101860

Start Date: 07-2020

End Date: 11-2023

Amount: $505,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP180103003

Start Date: 2018

End Date: 06-2021

Amount: $373,136.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157

Start Date: 2018

End Date: 12-2018

Amount: $600,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE190100130

Start Date: 2019

End Date: 12-2019

Amount: $1,480,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100043

Start Date: 2018

End Date: 12-2019

Amount: $435,279.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP210200642

Start Date: 10-2022

End Date: 10-2025

Amount: $584,875.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100156

Start Date: 2021

End Date: 12-2021

Amount: $289,500.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP170103704

Start Date: 07-2017

End Date: 07-2020

Amount: $288,500.00

Funder: Australian Research Council