ORCID Profile
0000-0002-0818-0443
Current Organisations
Linköpings universitet
,
National Heart Centre Singapore
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Publisher: Springer Science and Business Media LLC
Date: 06-2005
Publisher: American Chemical Society (ACS)
Date: 08-02-2018
DOI: 10.1021/ACS.ANALCHEM.7B03791
Abstract: As paper-based diagnostics has become predominantly driven by more advanced microfluidic technology, many of the research efforts are still focused on developing reliable and versatile fluidic control devices, apart from improving sensitivity and reproducibility. In this work, we introduce a novel and robust paper fluidic control system enabling versatile fluidic control. The system comprises a linear push-pull solenoid and an Arduino Uno microcontroller. The precisely controlled pressure exerted on the paper stops the flow. We first determined the stroke distance of the solenoid to obtain a constant pressure while examining the fluidic time delay as a function of the pressure. Results showed that strips of grade 1 chromatography paper had superior reproducibility in fluid transport. Next, we characterized the reproducibility of the fluidic velocity which depends on the type and grade of paper used. As such, we were able to control the flow velocity on the paper and also achieve a complete stop of flow with a pressure over 2.0 MPa. Notably, after the actuation of the pressure driven valve (PDV), the previously pressed area regained its original flow properties. This means that, even on a previously pressed area, multiple valve operations can be successfully conducted. To the best of our knowledge, this is the first demonstration of an active and repetitive valve operation in paper microfluidics. As a proof of concept, we have chosen to perform a multistep detection system in the form of an enzyme-linked immunosorbent assay with mouse IgG as the target analyte.
Publisher: SAGE Publications
Date: 10-2004
DOI: 10.1016/J.JALA.2004.07.008
Abstract: Automation will be a necessary step for the success of molecular computing. Here we have applied microfluidic technology to DNA computers, with a s le application towards solving Boolean logic problems.
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B617357H
Abstract: In this study, we introduce a microfluidic device equipped with pneumatically actuated valves, generating a linear gradient of chemoeffectors to quantify the chemotactic response of Tetrahymena pyriformis, a freshwater ciliate. The microfluidic device was fabricated from an elastomer, poly(dimethylsiloxane) (PDMS), using multi-layer soft lithography. The components of the device include electronically controlled pneumatic microvalves, microchannels and microchambers. The linear gradient of the chemoeffectors was established by releasing a chemical from a ciliate-free microchamber into a microchamber containing the ciliate. The ciliate showed chemotactic behaviours by either swimming toward or avoiding the gradient. By counting the number of ciliates residing in each microchamber, we obtained a precise time-response curve. The ciliates in the microfluidic device were sensitive enough to be attracted to 10 pmol glycine-proline, which indicates a 10(5) increase in the ciliate's known sensitivity. With the use of blockers, such as DL-2-amino-5-phosphonopentanoic acid (APPA) or lanthanum chloride (LaCl3), we have demonstrated that the NMDA (N-methyl-d-aspartate) receptor plays a critical role in the perception of chemoeffectors, whereas the Ca2+ channel is related to the motility of the ciliate. These results demonstrate that our microfluidic chemotaxis assay system is useful not only for the study of ciliate chemotaxis but also for a better understanding of the signal transduction mechanism on their receptors.
Publisher: Springer Science and Business Media LLC
Date: 12-2004
Publisher: Springer Berlin Heidelberg
Date: 2011
DOI: 10.1007/128_2011_147
Abstract: Microfluidic devices offer a realistic environment for cell cultures as it is related to scales found in biological systems. The aim is to create more in vivo like systems, in comparison to 2D plate cultures. Creating 3D cell culture constructs increase the cell's functionality. By controlling the microenvironment (e.g., cell matrix, flow rate, temperature) cell functionality can be increased even more. As microfluidic devices allow for precise control of the microenvironment, they are a paramount tool to study stem cells and their differentiation caused by external factors. We will give an overview of the use of microfluidic devices for some biological problems, and especially as a cell culture platforms. We focus on 3D cell cultures and stem cells and their microenvironment.
Publisher: Elsevier BV
Date: 03-2003
Publisher: IOP Publishing
Date: 21-02-2017
Abstract: The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.
Publisher: SPIE
Date: 16-02-2005
DOI: 10.1117/12.582210
Publisher: American Chemical Society (ACS)
Date: 04-10-2018
DOI: 10.1021/ACS.ANALCHEM.8B03532
Abstract: Cells were separated with the aid of a multistep spiral fractionation device, utilizing hydrodynamic forces in a spiral tubing. The spiral was fabricated using "off-the-shelf" microbore tubing, allowing for cheap and fast prototyping to achieve optimal cell separation. As a first step, a model system with 20 and 40 μm beads was used to demonstrate the effectiveness of the multistep separation device. With an initial purity of 5%, a separation purity of 83% was achieved after a two-step separation with the addition of 0.1% polyethylene glycol (PEG)-8000. Next, doxorubicin-resistant polyploid giant breast cancer cells (MDA-MB-231) were separated from doxorubicin-sensitive monoploid small breast cancer cells in the same fashion as the beads, resulting in a purity of around 40%, while maintaining a cell viability of more than 90%. Combined with basic cell analytical methods, the hydrodynamic separation principle of the device could be envisaged to be useful for a variety of cell fractionation needs in cell biology and in clinical applications.
Publisher: MDPI AG
Date: 14-10-2021
DOI: 10.3390/MI12101245
Abstract: Malaria affects 228 million people worldwide each year, causing severe disease and worsening the conditions of already vulnerable populations. In this review, we explore how malaria has been detected in the past and how it can be detected in the future. Our primary focus is on finding new directions for low-cost diagnostic methods that unspecialized personnel can apply in situ. Through this review, we show that microfluidic devices can help pre-concentrate s les of blood infected with malaria to facilitate the diagnosis. Importantly, these devices can be made cheaply and be readily deployed in remote locations.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2LC20677C
Abstract: Biomolecules inside a microfluidic system can be used to solve computational problems, such as theorem proving, which is an important class of logical reasoning problems. In this article, the Boolean variables (literals) were represented using single-stranded DNA molecules, and theorem proving was performed by the hybridization and ligation of these variables into a double-stranded "solution" DNA. Then, a novel sequential reaction mixing method in a microfluidic chip was designed to solve a theorem proving problem, where a reaction loop and three additional chambers were integrated and controlled by pneumatic valves. DNA hybridization, ligation, toehold-mediated DNA strand displacement, exonuclease I digestion, and fluorescence detection of the double-stranded DNA were sequentially performed using this platform. Depending on the computational result, detection of the correct answer was demonstrated based on the presence of a fluorescence signal. This result is the first demonstration that microfluidics can be used to facilitate DNA-based logical inference.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.BIOMATERIALS.2008.04.022
Abstract: 3D microfluidic cell culture systems offer a biologically relevant model to conduct micro-scale mammalian cell-based research and applications. Various natural and synthetic hydrogels have been successfully incorporated into microfluidic systems to support mammalian cells in 3D. However, embedment of cells in hydrogels introduces operational complexity, potentially hinders mass transfer, and is not suitable for establishing cell-dense, ECM-poor constructs. We present here a gel-free method for seeding and culturing mammalian cells three-dimensionally in a microfluidic channel. A combination of transient inter-cellular polymeric linker and micro-fabricated pillar arrays was used for the in situ formation and immobilization of 3D multi-cellular aggregates in a microfluidic channel. 3D cellular constructs formed this way are relieved of hydrogel embedment for cellular support. Two mammalian cell lines (A549 and C3A) and a primary mammalian cell (bone marrow mesenchymal stem cells) were cultured in the gel-free 3D microfluidic cell culture system. The cells displayed 3D cellular morphology, cellular functions and differentiation capability, affirming the versatility of the system as a 3D cell perfusion culture platform for anchorage-dependent mammalian cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B614872G
Abstract: Mammalian cells cultured on 2D surfaces in microfluidic channels are increasingly used in drug development and biological research applications. These systems would have more biological or clinical relevance if the cells exhibit 3D phenotypes similar to the cells in vivo. We have developed a microfluidic channel based system that allows cells to be perfusion-cultured in 3D by supporting them with adequate 3D cell-cell and cell-matrix interactions. The maximal cell-cell interaction was achieved by perfusion-seeding cells through an array of micropillars and 3D cell-matrix interactions were achieved by a polyelectrolyte complex coacervation process to form a thin layer of matrix conforming to the 3D cell shapes. Carcinoma cell lines (HepG2, MCF7), primary differentiated (hepatocytes) and primary progenitor cells (bone marrow mesenchymal stem cells) were perfusion-cultured for 72 hours to 1 week in the microfluidic channel, which preserved their 3D cyto-architecture and cell-specific functions or differentiation competence. This transparent 3D microfluidic channel-based cell culture system also allows direct optical monitoring of cellular events for a wide range of applications.
Publisher: Elsevier BV
Date: 06-2000
DOI: 10.1016/S0956-5663(00)00061-0
Abstract: The sensitivity of optical biosensors where the detection takes place on a planar gold surface can be improved by making the surface porous. The porosity allows a larger number of ligands per surface area resulting in larger optical shifts when interacting with specifically binding analyte molecules. The porous gold was deposited as a thin layer on a planar gold surface by electrochemical deposition in a solution of tetrachloroaurate and lead acetate. A protein, streptavidin, was adsorbed into the formed porous layer and the time course of the adsorption was monitored by in-situ ellipsometry. When the porous layer was 500 nm in thickness a six-fold increase of the ellipsometric response was obtained compared with a planar gold surface. The dependency of porosity and layer thickness was explained with a mathematical model of the gold orous gold rotein/solution system.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1LC20351G
Abstract: We have developed a multi-channel microfluidic perfusion platform for culturing zebrafish embryos and capturing live images of various tissues and organs inside the embryo. The Fish and Chips was micro-fabricated in silicon and glass for reproducibility and accuracy of the microfluidic structure. The microfluidic platform consists of three parts: a microfluidic gradient generator, a row of eight fish tanks, in which the fish embryos are in idually placed, and eight output channels. The fluidic gradient generator supports dose-dependent drug and chemical studies. A unique perfusion system ensures a uniform and constant flow of media to the fish tank while the wastes are efficiently removed. The fish tanks restrict the embryo movements, except rotationally, for live imaging of internal tissues and organs. The embryos showed developmental abnormalities under the influence of the drug valproic acid (VPA).
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B814371D
Abstract: We present a novel active mixing method in a microfluidic chip, where the controlled stirring of magnetic particles is used to achieve an effective mixing of fluids. To perform mixing, the ferromagnetic particles were embedded and manipulated under the influence of a rotating magnetic field. By aligning the magnetic beads along the magnetic field lines, rod-like structures are formed, functioning as small stir bars. Under higher flow conditions the particles did not form the typical rod structure but rather formed aggregates, which were even more beneficial for mixing. Our system reached a 96% mixing efficiency in a relatively short distance (800 microm) at a flow rate of 1.2-4.8 mm/s. These results demonstrate that our mixing method is useful for microfluidic devices with low aspect ratios and molecules with large molecular weights.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.BIOS.2014.01.039
Abstract: Protein kinases control cellular functions by regulating protein phosphorylation. Monitoring protein kinase activity is essential for medical diagnosis and drug screening. Here, we present a novel microfluidic device for performing simple and versatile protein kinase assays, which utilizes a microbead-based chemosensor. An automatic mix-and-measure technique was achieved using integrated pneumatic valves. After mixing each reagent for the kinase assay, the mixture was transferred to the sensing chamber. Then, phosphorylated and fluorescence-labeled peptides were captured and detected by the chemosensor. A fluorescence signal was observed depending on the presence of the kinase. Furthermore, activities of various kinases in the cell lysate and the inhibitory effect of specific chemicals on the kinases were monitored. These results indicate that chemosensor-based microfluidic chips can be developed as a versatile kinase assay system.
Publisher: IOP Publishing
Date: 24-05-2000
Publisher: IEEE
Date: 09-2007
Publisher: Wiley
Date: 04-02-2013
DOI: 10.1002/BIT.24822
Abstract: In vitro drug testing requires long-term maintenance of hepatocyte liver specific functions. Hepatocytes cultured at a higher seeding density in a sandwich configuration exhibit an increased level of liver specific functions when compared to low density cultures due to the better cell to cell contacts that promote long term maintenance of polarity and liver specific functions. However, culturing hepatocytes at high seeding densities in a standard 24-well plate poses problems in terms of the mass transport of nutrients and oxygen to the cells. In view of this drawback, we have developed a polydimethylsiloxane (PDMS) bioreactor that was able to maintain the long-term liver specific functions of a hepatocyte sandwich culture at a high seeding density. The bioreactor was fabricated with PDMS, an oxygen permeable material, which allowed direct oxygenation and perfusion to take place simultaneously. The mass transport of oxygen and the level of shear stress acting on the cells were analyzed by computational fluid dynamics (CFD). The combination of both direct oxygenation and perfusion has a synergistic effect on the liver specific function of a high density hepatocyte sandwich culture over a period of 9 days.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.BBRC.2011.04.044
Abstract: Microfluidics is a convenient platform to study the influences of fluid shear stress on calcium dynamics. Fluidic shear stress has been proven to affect bone cell functions and remodelling. We have developed a microfluidic system which can generate four shear flows in one device as a means to study cytosolic calcium concentration ([Ca(2+)](c)) dynamics of osteoblasts. Four shear forces were achieved by having four cell culture chambers with different widths while resistance correction channels compensated for the overall resistance to allow equal flow distribution towards the chambers. Computational simulation of the local shear stress distribution highlighted the preferred section in the cell chamber to measure the calcium dynamics. Osteoblasts showed an [Ca(2+)](c) increment proportional to the intensity of the shear stress from 0.03 to 0.30 Pa. A delay in response was observed with an activation threshold between 0.03 and 0.06 Pa. With computational modelling, our microfluidic device can offer controllable multishear stresses and perform quantitative comparisons of shear stress-induced intensity change of calcium in osteoblasts.
Publisher: IOP Publishing
Date: 20-09-2002
Publisher: Elsevier BV
Date: 1988
Publisher: Springer Science and Business Media LLC
Date: 27-11-2013
DOI: 10.1038/SREP03247
Publisher: Springer Berlin Heidelberg
Date: 2002
Publisher: MDPI AG
Date: 21-02-2020
DOI: 10.3390/S20041202
Abstract: Molecular diagnostics for sepsis is still a challenge due to the presence of compounds that interfere with gene lification and bacteria at concentrations lower than the limit of detection (LOD). Here, we report on the development of a 3D printed modular microfluidic device (3DpmμFD) that preconcentrates bacteria of interest in whole blood and purifies their genomic DNA (gDNA). It is composed of a W-shaped microchannel and a conical microchamber. Bacteria of interest are magnetically captured from blood in the device with antibody conjugated magnetic nanoparticles (Ab-MNPs) at 5 mL/min in the W-shaped microchannel, while purified gDNA of the preconcentrated bacteria is obtained with magnetic silica beads (MSBs) at 2 mL/min in the conical microchamber. The conical microchamber was designed to be connected to the microchannel after the capturing process using a 3D-printed rotary valve to minimize the exposure of the MSBs to interfering compounds in blood. The pretreatment process of spiked blood (2.5 mL) can be effectively completed within about 50 min. With the 3DpmμFD, the LOD for the target microorganism Escherichia coli O157:H7 measured by both polymerase chain reaction (PCR) with electrophoresis and quantitative PCR was 10 colony forming unit (CFU) per mL of whole blood. The results suggest that our method lowers the LOD of molecular diagnostics for pathogens in blood by providing bacterial gDNA at high purity and concentration.
Publisher: MDPI AG
Date: 16-12-2021
Abstract: Extracellular vesicles (EVs) are a group of membrane vesicles that play important roles in cell-to-cell and interspecies/interkingdom communications by modulating the pathophysiological conditions of recipient cells. Recent evidence has implied their potential roles in the gut–brain axis (GBA), which is a complex bidirectional communication system between the gut environment and brain pathophysiology. Despite the evidence, the roles of EVs in the gut microenvironment in the GBA are less highlighted. Moreover, there are critical challenges in the current GBA models and analyzing techniques for EVs, which may hinder the research. Currently, advances in organ-on-a-chip (OOC) technologies have provided a promising solution. Here, we review the potential effects of EVs occurring in the gut environment on brain physiology and behavior and discuss how to apply OOCs to research the GBA mediated by EVs in the gut microenvironment.
Publisher: Wiley
Date: 11-01-2008
Publisher: IEEE
Date: 2003
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.BIOMATERIALS.2009.03.052
Abstract: 3D-microfluidic cell culture systems (3D-microFCCSs) support hepatocyte functions in vitro which can be further enhanced by controlled presentation of 100-200 pg/ml TGF-beta1, thus mimicking the roles of supporting cells in co-cultures. Controlled presentation of TGF-beta1 is achieved by either direct perfusion or in situ controlled release from gelatin microspheres immobilized in the 3D-microFCCS. Primary hepatocytes cultured for 7 days with the in situ controlled released TGF-beta1 exhibited up to four-fold higher albumin secretion and two-fold higher phase I/II enzymatic activities, significantly improving the sensitivity of hepatocytes to acetaminophen-mediated hepatotoxicity, compared to hepatocytes cultured with directly perfused TGF-beta1 or without TGF-beta1. The controlled presentation of TGF-beta1 enhanced hepatocyte functions in microfluidic systems without the complications of co-cultures, allowing for simplifications in drug testing and other hepatocyte-based applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1LC90044G
Publisher: MDPI AG
Date: 16-02-2020
DOI: 10.3390/MI11020203
Abstract: Influenza A viruses are often present in environmental and clinical s les at concentrations below the limit of detection (LOD) of molecular diagnostics. Here we report an integrated microfluidic preconcentration and nucleic lification system (μFPNAS) which enables both preconcentration of influenza A virus H1N1 (H1N1) and lification of its viral RNA, thereby lowering LOD for H1N1. H1N1 virus particles were first magnetically preconcentrated using magnetic nanoparticles conjugated with an antibody specific for the virus. Their isolated RNA was lified to cDNA through thermocycling in a trapezoidal chamber of the μFPNAS. A detection limit as low as 100 TCID50 (50% tissue culture infective dose) in saliva can be obtained within 2 hours. These results suggest that the LOD of molecular diagnostics for virus can be lowered by systematically combining immunomagnetic separation and reverse transcriptase-polymerase chain reaction (RT-PCR) in one microfluidic device.
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0956-5663(97)00094-8
Abstract: Porous silicon dioxide surfaces have been used for monitoring the specific affinity binding of low molecular weight molecules to streptavidin. Streptavidin was immobilized to the porous silicon dioxide surface by spontaneous adsorption at pH 7.4. Binding of biotin and an oligopeptide synthesized by means of combinatorial chemistry were monitored with an in situ null ellipsometer. Measurements were also done with hydroxy-azobenzene-2-carboxylic acid and DL-6-8-thioctic acid amide. The performance of porous silicon dioxide as a potential surface in biosensor applications was compared with a planar silicon dioxide surface. Porous silicon dioxide showed a 10-fold lification of the response compared to planar silicon dioxide. It was possible to monitor the binding of biotin and the oligopeptide in the concentration range 2-40 microM. A response time as low as 30 s was obtained for the oligopeptide at 40 microM.
Publisher: Springer Berlin Heidelberg
Date: 2005
DOI: 10.1007/11493785_32
Publisher: Springer Berlin Heidelberg
Date: 2006
DOI: 10.1007/11753681_30
Publisher: Springer Berlin Heidelberg
Date: 2006
DOI: 10.1007/11925903_22
Publisher: American Chemical Society (ACS)
Date: 11-07-2014
DOI: 10.1021/NL5008773
Abstract: The combination of micropillar array technology to measure cellular traction forces with super-resolution imaging allowed us to obtain cellular traction force maps and simultaneously zoom in on in idual focal adhesions with single-molecule accuracy. We achieved a force detection precision of 500 pN simultaneously with a mean single-molecule localization precision of 30 nm. Key to the achievement was a two-step etching process that provided an integrated spacer next to the micropillar array that permitted stable and reproducible observation of cells on micropillars within the short working distance of a high-magnification, high numerical aperture objective. In turn, we used the technology to characterize the super-resolved structure of focal adhesions during force exertion. Live-cell imaging on MCF-7 cells demonstrated the applicability of the inverted configuration of the micropillar arrays to dynamics measurements. Forces emanated from a molecular base that was localized on top of the micropillars. What appeared as a single adhesion in conventional microscopy were in fact multiple elongated adhesions emanating from only a small fraction of the adhesion on the micropillar surface. Focal adhesions were elongated in the direction of local cellular force exertion with structural features of 100-280 nm in 3T3 Fibroblasts and MCF-7 cells. The combined measure of nanoscale architecture and force exerted shows a high level of stress accumulation at a single site of adhesion.
Publisher: Future Medicine Ltd
Date: 03-2018
Abstract: Microfabrication and microfluidics contribute to the research of cellular functions of cells and their interaction with their environment. Previously, it has been shown that microfluidics can contribute to the isolation, selection, characterization and migration of cells. This review aims to provide stem cell researchers with a toolkit of microtechnology (mT) instruments for elucidating complex stem cells functions which are challenging to decipher with traditional assays and animal models. These microdevices are able to investigate about the differentiation and niche interaction, stem cells transcriptomics, therapeutic functions and the capture of their secreted microvesicles. In conclusion, microtechnology will allow a more realistic assessment of stem cells properties, driving and accelerating the translation of regenerative medicine approaches to the clinic.
Publisher: Wiley
Date: 2009
DOI: 10.1002/BTPR.171
Abstract: With the introduction of microtechnology and microfluidic platforms for cell culture, stem cell research can be put into a new context. Inside microfluidics, microenvironments can be more precisely controlled and their influence on cell fate studied. Microfluidic devices can be made transparent and the cells monitored real time by imaging, using fluorescence markers to probe cell functions and cell fate. This article gives a perspective on the yet untapped utility of microfluidic devices for stem cell research. It will guide the biologists through some basic microtechnology and the application of microfluidics to cell research, as well as highlight to the engineers the cell culture capabilities of microfluidics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B915147H
Abstract: We have developed a multi-channel 3D microfluidic cell culture system (multi-channel 3D-microFCCS) with compartmentalized microenvironments for potential application in human drug screening. To this end, the multi-channel 3D-microFCCS was designed for culturing different 3D cellular aggregates simultaneously to mimic multiple organs in the body. Four human cell types (C3A, A549, HK-2 and HPA) were chosen to represent the liver, lung, kidney and the adipose tissue, respectively. Cellular functions were optimized by supplementing the common medium with growth factors. However, TGF-beta1 was found to enhance A549 functions but inhibit C3A functions. Therefore, TGF-beta1 was specifically controlled-released inside the A549 compartment by means of gelatin microspheres mixed with cells, thus creating a cell-specific microenvironment. The function of A549 cells was enhanced while the functions of C3A, HK-2 and HPA cells were uncompromised, demonstrating the limited cross-talk between cell culture compartments similar to the in vivo situation. Such a multi-channel 3D-microFCCS could be potentially used to supplement or even replace animal models in drug screening.
Publisher: Springer Berlin Heidelberg
Date: 2004
Publisher: IOP Publishing
Date: 26-05-2017
Abstract: Mechatronic design is an engineering methodology for conceiving, configuring and optimising the design of a technical device or product to the needs and requirements of the final user. In this article, we show how the basic principles of this methodology can be exploited for in vitro cell cultures-often referred to as organ-on-a-chip devices. Due to the key role of the biological cells, we have introduced the term bio-mechatronic design, to highlight the complexity of designing a system that should integrate biology, mechanics and electronics in the same device structure. The strength of the mechatronic design is to match the needs of the potential users to a systematic evaluation of overall functional design alternative. It may be especially attractive for organs-on-chips where biological constituents such as cells and tissues in 3D settings and in a fluidic environment should be compared, screened and selected. Through this approach, design solutions ranked to customer needs are generated according to specified criteria, thereby defining the key constraints of the fabrication. As an ex le, the bio-mechatronic methodology is applied to a liver-on-a-chip based on information extrapolated from previous theoretical and experimental knowledge. It is concluded that the methodology can generate new fabrication solutions for devices, as well as efficient guidelines for refining the design and fabrication of many of today's organ-on-a-chip devices.
Publisher: EDP Sciences
Date: 12-1988
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B900912D
Abstract: We have developed a microfluidic 3D hepatocyte chip (3D HepaTox Chip) for in vitro drug toxicity testing to predict in vivo drug hepatotoxicity. The 3D HepaTox Chip is based on multiplexed microfluidic channels where a 3D microenvironment is engineered in each channel to maintain the hepatocytes' synthetic and metabolic functions. The multiplexed channels allow for simultaneous administration of multiple drug doses to functional primary hepatocytes while an incorporated concentration gradient generator enables the in vitro dose-dependent drug responses to predict in vivo hepatotoxicity. The IC(50) values of 5 model drugs derived from the dose-dependent on-chip testing correlate well with the reported in vivo LD(50) values. The 3D HepaTox Chip can be integrated with on-chip sensors and actuators as the next generation cell-based on-chip drug testing platform.
Publisher: American Chemical Society (ACS)
Date: 21-10-2019
DOI: 10.1021/ACS.ANALCHEM.9B03722
Abstract: Pipetting techniques play a crucial role in obtaining reproducible and reliable results, especially when seeding cells on small target areas, such as on microarrays, biochips or microfabricated cell culture systems. For very rare cells, such as human primary skeletal muscle cells (skMCs), manual (freehand) cell seeding techniques invariably result in nonuniform cell spreading and heterogeneous cell densities, giving rise to undesirable variations in myogenesis and differentiation. To prevent such technique-dependent variation, we have designed and fabricated a simple, low-cost pipet guidance device (PGD), and holder that works with hand-held pipettes. This work validates the accuracy and reproducibility of the PGD platform and compares its effectiveness with manual and robotic seeding techniques. The PGD system ensures reproducibility of cell seeding, comparable to that of more expensive robotic dispensing systems, resulting in a high degree of cell uniformity and homogeneous cell densities, while also enabling cell community studies. As compared to freehand pipetting, PGD-assisted seeding of C2C12 mouse myoblasts showed 5.3 times more myotube formation and likewise myotubes derived from PGD-seeded human primary skMCs were 3.6 times thicker and 2.2 times longer. These results show that this novel, yet simple PGD-assisted pipetting technique provides precise cell seeding on small targets, ensuring reproducible and reliable high-throughput cell assays.
Publisher: Springer Science and Business Media LLC
Date: 06-2001
Publisher: SPIE
Date: 19-11-2001
DOI: 10.1117/12.454623
Publisher: MDPI AG
Date: 08-04-2018
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.BIOMATERIALS.2009.10.049
Abstract: Three-dimensional (3D) in vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in vivo conditions. In cancer research, the multi-cellular tumor spheroid (MCTS) model is an established 3D cancer model that exhibits microenvironmental heterogeneity close to that of tumors in vivo. However, the established process of MCTS formation is time-consuming and often uncontrolled. Here, we report a method for engineering MCTS using a transient inter-cellular linker which facilitates cell-cell interaction. Using C3A cells (a hepatocellular carcinoma cell line) as a model, we formed linker-engineered spheroids which grew to a diameter of 250 microm in 7 days, as compared to 16 days using conventional non-adherent culture. Seven-day old linker-engineered spheroids exhibited characteristics of mature MCTS, including spheroid morphology, gene expression profile, cell-cell interaction, extracellular matrix secretion, proliferation and oxygen concentration gradients, and cellular functions. Linker-engineered spheroids also displayed a resistance to drug penetration similar to mature MCTS, with dose-dependent extracellular accumulation of the drug. The linker-engineered spheroids thus provide a reliable accelerated 3D in vitro tumor model for drug penetration studies.
Location: Singapore
Location: Korea, Republic of
Location: Singapore
No related grants have been discovered for Danny van Noort.