ORCID Profile
0000-0001-8099-3863
Current Organisations
Columbia University
,
University of Queensland
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Nanomaterials | Nanotechnology | Sensor Technology (Chemical aspects) | Nanobiotechnology |
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology
Publisher: Springer Science and Business Media LLC
Date: 04-12-2018
DOI: 10.1038/S41467-018-07214-W
Abstract: Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as Methylscape is displayed by most cancer types, thus may serve as a universal cancer biomarker. To-date most research has focused on the biological consequences of DNA Methylscape changes whereas its impact on DNA physicochemical properties remains unexplored. Herein, we examine the effect of levels and genomic distribution of methylcytosines on the physicochemical properties of DNA to detect the Methylscape biomarker. We find that DNA polymeric behaviour is strongly affected by differential patterning of methylcytosine, leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes. We exploit these Methylscape differences to develop simple, highly sensitive and selective electrochemical or colorimetric one-step assays for the detection of cancer. These assays are quick, i.e., analysis time ≤10 minutes, and require minimal s le preparation and small DNA input.
Publisher: Elsevier BV
Date: 04-2019
Publisher: MDPI AG
Date: 04-02-2022
DOI: 10.3390/EPIGENOMES6010006
Abstract: The efficiency of conventional screening programs to identify early-stage malignancies can be limited by the low number of cancers recommended for screening as well as the high cumulative false-positive rate, and associated iatrogenic burden, resulting from repeated multimodal testing. The opportunity to use minimally invasive liquid biopsy testing to screen asymptomatic in iduals at-risk for multiple cancers simultaneously could benefit from the aggregated diseases prevalence and a fixed specificity. Increasing both latter parameters is paramount to mediate high positive predictive value—a useful metric to evaluate a screening test accuracy and its potential harm-benefit. Thus, the use of a single test for multi-cancer early detection (stMCED) has emerged as an appealing strategy for increasing early cancer detection rate efficiency and benefit population health. A recent flurry of these stMCED technologies have been reported for clinical potential however, their development is facing unique challenges to effectively improve clinical cost–benefit. One promising avenue is the analysis of circulating tumour DNA (ctDNA) for detecting DNA methylation biomarker fingerprints of malignancies—a hallmark of disease aetiology and progression holding the potential to be tissue- and cancer-type specific. Utilizing panels of epigenetic biomarkers could potentially help to detect earlier stages of malignancies as well as identify a tumour of origin from blood testing, useful information for follow-up clinical decision making and subsequent patient care improvement. Overall, this review collates the latest and most promising stMCED methodologies, summarizes their clinical performances, and discusses the specific requirements multi-cancer tests should meet to be successfully implemented into screening guidelines.
Publisher: IEEE
Date: 12-2015
Publisher: Wiley
Date: 19-07-2023
Abstract: Tumor cells display heterogenous molecular signatures during the course of cancer and create distinct tumor cell subpopulations which challenge effective therapeutic decisions. Detection and monitoring of these heterogenous molecular events at single cell level are imperative to identify tumor cell subpopulations and to engage the best therapeutic options for the in idual patient. Herein, a microfluidic liquid biopsy platform to analyze circulating tumor cells (CTCs) at single cell level is reported. The in idual CTCs are captured in an alternating current‐induced microfluidic platform and analyzed by using surface‐enhanced Raman scattering spectroscopy. This platform selectively captures single CTCs from the patient's peripheral blood mononuclear cells. Using cell line models and patient s les, it is shown that the assay can simultaneously detect multiple protein biomarkers on a single CTC. The platform can stratify the CTCs into different subpopulations based on their cancer‐associated protein signature changes in response to drug treatment. This enables the identification of CTC subpopulations that are probably not responding to treatment and may assist clinicians in specifically monitoring and eliminating therapy‐resistant cancer cells within a lesion. This single CTC monitoring chip will likely have high clinical importance in disease diagnosis and treatment monitoring, and advance the knowledge of cancer heterogeneity.
Publisher: American Chemical Society (ACS)
Date: 29-09-2014
DOI: 10.1021/AC502214Z
Abstract: The analysis of DNA methylation is becoming increasingly important both in the clinic and also as a research tool to unravel key epigenetic molecular mechanisms in biology. Current methodologies for the quantification of regional DNA methylation (i.e., the average methylation over a region of DNA in the genome) are largely affected by comprehensive DNA sequencing methodologies which tend to be expensive, tedious, and time-consuming for many applications. Herein, we report an alternative DNA methylation detection method referred to as "Methylsorb", which is based on the inherent affinity of DNA bases to the gold surface (i.e., the trend of the affinity interactions is adenine > cytosine ≥ guanine > thymine).1 Since the degree of gold-DNA affinity interaction is highly sequence dependent, it provides a new capability to detect DNA methylation by simply monitoring the relative adsorption of bisulfite treated DNA sequences onto a gold chip. Because the selective physical adsorption of DNA fragments to gold enable a direct read-out of regional DNA methylation, the current requirement for DNA sequencing is obviated. To demonstrate the utility of this method, we present data on the regional methylation status of two CpG clusters located in the EN1 and MIR200B genes in MCF7 and MDA-MB-231 cells. The methylation status of these regions was obtained from the change in relative mass on gold surface with respect to relative adsorption of an unmethylated DNA source and this was detected using surface plasmon resonance (SPR) in a label-free and real-time manner. We anticipate that the simplicity of this method, combined with the high level of accuracy for identifying the methylation status of cytosines in DNA, could find broad application in biology and diagnostics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8LC00991K
Abstract: We report an integrated multi-molecular sensor (IMMS) platform for an entire s le-to-answer protocol encompassing melanoma cell capture in biological fluids, on-chip cell lysis, and combined quantification of intracellular BRAF V600E DNA and protein amounts.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.BIOTECHADV.2018.11.010
Abstract: Assessing T-cell mediated immune status can help to understand the body's response to disease and also provide essential diagnostic information. However, detection and characterization of immune response are challenging due to the rarity of signature biomolecules in biological fluid and require highly sensitive and specific assay technique for the analysis. Until now, several techniques spanning from flow cytometry to microsensors have been developed or under investigation for T-cell mediated immune response monitoring. Most of the current assays are designed to estimate average immune responses, i.e., total functional protein analysis and detection of total T-cells irrespective of their antigen specificity. Although potential, immune response analysis without detecting and characterizing the rare subset of T-cell population could lead to over or underestimation of patient's immune status. Addressing this limitation, recently a number of technological advancements in biosensing have been developed for this. The potential of simple and precise micro-technologies including microarray and microfluidic platforms for assessing antigen-specific T-cells will be highlighted in this review, together with a discussion on existing challenges and future aspects of immune-sensor development.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2014
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.MOLMED.2019.05.014
Abstract: Eukaryotic cell DNA conserves a distinct genomic methylation pattern, which acts as a molecular switch to control the transcriptional machinery of the cell. However, pathological processes can alter this methylation pattern, leading to the onset of diseases such as cancer. Recent advances in methylation analysis provide a more precise understanding of the consequence of DNA methylation changes towards cancer progression. Consequently, the discoveries of numerous methylation-based biomarkers have inspired the development of simple tests for cancer detection. In this opinion article, we systematically discuss the benefits and challenges associated with the promising methylation-based approaches and develop a point-of-care index to evaluate their potential in terms of point-of-care cancer diagnostics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9AN02106J
Abstract: Raman tag intercalated short-length DNA and dual nanoplatform based SERS DNA biosensor for the ultrasensitive and selective detection of DNA.
Publisher: Bangladesh Journals Online (JOL)
Date: 28-12-2014
Abstract: A ferrocenyl imine complex, Fc-C(CH3)=N-NH-C6H3-2,4-(NO2)2 (Fc = ferrocenyl) has been synthesized by the condensation reaction between acetylferrocene and 2,4-dinitrophenyl hydrazine. The compound was synthesised previously, and characterized by IR, 1H and elemental analysis. It was further characterized by 13C {1H} NMR spectroscopy and mass spectrometry. The redox property of the complex was studied by cyclic voltammetry, differential pulse voltammetry and chronocoulometry. The redox process of the complex was found to be reversible at a platinum-disc electrode, and the redox potential of the imine complex was shifted to more anodic position with respect to ferrocene. The redox reactivity of the complex was enhanced in the presence of oxygen. DOI: 0.3329/jbas.v38i2.21342 Journal of Bangladesh Academy of Sciences, Vol. 38, No. 2, 177-187, 2014
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NR09496E
Abstract: Interfacial nanomixing enhances the adsorption of cancer biomarkers and enables in situ electrochemical detection in a multiplexed device.
Publisher: Elsevier
Date: 2018
Publisher: American Chemical Society (ACS)
Date: 06-07-0016
Abstract: Cancer is a dynamic disease with heterogenic molecular signatures and constantly evolves during the course of the disease. Single cell proteomic analysis could offer a suitable pathway to monitor cancer cell heterogeneity and deliver critical information for the diagnosis, recurrence, and drug-resistant mechanisms in cancer. Current standard techniques for proteomic analysis such as ELISA, mass spectrometry, and Western blots are time-consuming, expensive, and often require fluorescence labeling that fails to provide accurate information about the multiple protein expression changes at the single cell level. Herein, we report a surface-enhanced Raman spectroscopy-based simple microfluidic device that enables the screening of single circulating tumor cells (CTC) in a dynamic state to precisely understand the heterogeneous expression of multiple protein biomarkers in response to therapy. It further enables identifying intercellular heterogeneous expression of CTC surface proteins which would be highly informative to identify the cancer cells surviving treatment and potentially responsible for drug resistance. Using a bead and cell line-based model system, we successfully detect single bead and single cell spectra when flowed through the device. Using SK-MEL-28 melanoma cells, we demonstrate that our system is capable of monitoring heterogeneous expressions of multiple surface protein markers (MCSP, MCAM, and LNGFR) before and during drug treatment. Integrating a label-free electrochemical system with the device, we also monitor the expression of an intracellular protein (here, BRAF V600E ) under drug treatment. Finally, we perform a longitudinal study with 15 s les from five different melanoma patients who underwent therapy. We find that the average expression of receptor proteins in a patient fails to determine the therapy response particularly when the disease progresses. However, single CTC analysis with our device shows a high level of intercellular heterogeneity in the receptor expression profiles of patient-derived CTCs and identifies heterogeneity within CTCs. More importantly, we find that a fraction of CTCs still shows a high expression of these receptor proteins during and after therapy, indicating the presence of resistant CTCs which may evolve after a certain time and progress the disease. We believe this automated assay will have high clinical importance in disease diagnosis and monitoring treatment and will significantly advance the understanding of cancer heterogeneity on the single cell level.
Publisher: American Chemical Society (ACS)
Date: 24-05-2023
Publisher: Springer Science and Business Media LLC
Date: 17-02-2021
DOI: 10.1038/S41467-021-21431-W
Abstract: The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.
Publisher: MDPI AG
Date: 28-02-2022
DOI: 10.3390/CHEMOSENSORS10030093
Abstract: Detecting circulating biomarkers sensitively and quantitatively is paramount for cancer screening, diagnosis, and treatment selection. Particularly, screening of a panel of circulating protein biomarkers followed by mapping of in idual biomarkers could assist better diagnosis and understanding of the cancer progression mechanisms. Herein, we present a miniaturized biosensing platform with dual readout schemes (electrochemical and Surface enhanced Raman scattering (SERS)) for rapid cancer screening and specific biomarker expressional profiling to support cancer management. Our approach utilizes a controlled nanomixing phenomena under alternative current electrohydrodynamic condition to improve the isolation of cancer-associated circulating proteins (i.e., Epidermal growth factor receptor (EGFR), BRAF, Programmed death-ligand 1 (PD-L1)) with antibody functionalized sensor surface for rapid and efficient isolation of the targets and subsequent labelling with SERS nanotags. The method employs Differential Pulse Voltammetry (DPV) for rapidly screening for the presence of the circulating proteins on biosensor surface irrespective of their type. Upon positive DPV detection, SERS is applied for sensitive read-out of in idual biomarkers biomarker levels. In a proof-of-concept study, we demonstrate the dual detection biosensor for analysing circulating BRAF, EGFR and PDL-1 proteins and successfully screened both ensemble and in idual biomarker expressional levels as low as 10 pg (1 ng/mL). Our findings clearly indicate the potential of the proposed method for cancer biomarker analysis which may drive the translation of this dual sensing concept in clinical settings.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2019
DOI: 10.1007/S00216-019-01608-5
Abstract: The development of a sensitive and specific detection platform for exosomes is highly desirable as they are believed to transmit vital tumour-specific information (mRNAs, microRNAs, and proteins) to remote cells for secondary metastasis. Herein, we report a simple method for the real-time and label-free detection of clinically relevant exosomes using a surface plasmon resonance (SPR) biosensor. Our method shows high specificity in detecting BT474 breast cancer cell-derived exosomes particularly from complex biological s les (e.g. exosome spiked in serum). This approach exhibits high sensitivity by detecting as low as 8280 exosomes/μL which may potentially be suitable for clinical analysis. We believe that this label-free and real-time method along with the high specificity and sensitivity may potentially be useful for clinical settings.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0AN01096K
Abstract: A nanostructured mesoporous gold electrode is demonstrated to detect the phosphorylated protein over non-phosphorylated in cancer using electrochemical signal lification through differential pulse voltammetry in the presence of the [Fe(CN) 6 ] 3−/4− .
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8NR02886A
Abstract: Monitoring of circulating cancer biomarkers was enabled in a graphene oxide functionalised ac-EHD microfluidic device with SERS barcoding.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC06732K
Abstract: Base dependent affinity interaction of DNA with gold has been utilised to electrochemically quantify the methylation status of bisulphite treated DNA s les.
Publisher: MDPI AG
Date: 18-04-2021
Abstract: Polyimide-silica (PI-Silica) composites are of tremendous research interest as high-performance materials because of their excellent thermal and mechanical properties and chemical resistance to organic solvents. Particularly, the sol-gel method of fabricating such composites is popular for manipulating their properties. In this work, PI-silica composite films are synthesized by the sol-gel method and thermal imidization from the solution mixtures of hydrolyzed tetraethoxysilane (TEOS) (or glycidoxypropyltrimethoxysilane (GPMS)) modified silica and an aromatic polyamic acid (PAA) based on 3,3′,4,4′-biphenyl tetracarboxylic dianhydride (BPDA)–p-phenylenediamine (PDA). The phase morphology of composites is found to be controlled by the substitution of TEOS with GPMS. Solid-state NMR spectroscopy is used to confirm the structural components of silica and GPMS-modified silica, whereas FT-IR results confirm the complete imidization of polyimide and composite film and suggest successful incorporation of Si–O–Si bonds into polyimide. The thermal, optical transmittance, and dielectric constant characterizations of pure polyimide and composite films are also carried out. Thermal stability of pure polyimide is found to be increased significantly by the addition of silica, whereas the partial substitution of TEOS with GPMS decreases the thermal stability of the composite, due to the presence of the alkyl organic segment of GPMS. The optical transmittance and dielectric constant of the composite films are controlled by manipulating the GPMS content.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9AN01450K
Abstract: A nanofluidic mixing-enhanced biosensor enables parallel detection of soluble PD-1, PD-L1, and LAG-3 immune checkpoints in minute liquid biopsy s les.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7AN00611J
Abstract: We report a new multiplexed strategy for the electrochemical detection of regional DNA methylation across multiple regions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1MA00848J
Abstract: Liquid biopsy-based diagnosis in precision oncology exhibits significant advantages over the traditional tissue biopsies by offering dynamic assessment of tumour heterogeneity, minimally invasive procedures for frequent s ling, and cost-effective tests.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.BIOS.2018.10.044
Abstract: Immune checkpoint blockade therapies are promising next generation immunotherapeutic treatments for cancer. Whilst sequential solid biopsies are an invaluable source of prognostic information, they are not feasible for monitoring therapeutic outcomes over time. Monitoring soluble immune checkpoint markers expression in body fluids could potentially be a better alternative. Current methods (e.g. ELISA) for detecting immune-checkpoint proteins mostly rely on the use of monoclonal antibodies which are expensive and time-consuming to manufacture and isolate. Herein, we report an integrated surface enhanced Raman scattering (SERS)-microfluidics device for the detection of immune checkpoint proteins which involves the use of i) nano yeast single chain variable fragment (scFv) as a promising alternative to monoclonal antibodies providing high stability at relative low-cost and simplicity for production, ii) graphene oxide functionalised surface to reduces the bio functionalization steps, thus avoiding the general paradigm of biotin-streptavidin chemistry and iii) a microfluidic platform enabling alternating current electrohydrodynamics (ac-EHD) induced nanomixing to enhance the target scFv binding and minimize the non-specific interactions. Specific and multiplex detection of immune checkpoint biomarkers is achieved by SERS based spectral encoding. Using this platform, we successfully demonstrated the detection of clinically relevant soluble immune checkpoints PD-1, PD-L1 and LAG-3 from as low as 100 fg/mL of analytes spiked in human serum.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3CC49607D
Abstract: DNA regional methylation can be detected in real-time and label-free using surface plasmon resonance biosensing coupled to molecular inversion probe based lification.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.BIOS.2016.12.012
Abstract: Protein phosphorylation is one of the most prominent post-translational mechanisms for protein regulation, which is frequently impaired in cancer. Through the covalent addition of phosphate groups to certain amino-acids, the interactions of former residues with nearby amino-acids are drastically altered, resulting in major changes of protein conformation that impacts its biological function. Herein, we report that these conformational changes can also disturb the protein's ability to interact with and adsorb onto bare gold surfaces. We exploited this feature to develop a simple electrochemical method for detecting the aberrant phosphorylation of EGFR protein in several lung cancer cell lines. This method, which required as low as 10ng/µL (i.e., 50ng) of purified EGFR protein, also enabled monitoring cell sensitivity to tyrosine kinase inhibitors (TKI) - a common drug used for restoring the function of aberrantly phosphorylated proteins in lung cancer. The reported strategy based on direct gold-protein affinity interactions avoids the conventional paradigm of requiring a phospho-specific antibody for detection and could be a potential alternative of widely used mass spectrometry.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5AY01479D
Abstract: Sequence-dependent non-thiolated DNA–gold affinity interaction for biosensing applications, and the underlying principles governing these interactions are comprehensively reviewed.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-02-2020
Abstract: An extracellular vesicle phenotype analyzer chip shines a light on patients’ responses to targeted therapy in cancer.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6AN00528D
Abstract: New electrochemical method to detect glycosylation of protein using lectin and protein gold interaction.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4AN01641F
Abstract: A simple, sensitive and inexpensive electrochemical method has been reported to detect regional DNA methylation by using differential adsorption affinity of DNA bases to gold.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2016
DOI: 10.1038/SREP30460
Abstract: Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological s les could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-in idual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves ( i ) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and ( ii ) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from s les containing designated proportions of HER2(+) BT474 and HER2(−) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient s les and identified that approximately 14–35% of their bulk population express HER2.
Publisher: MDPI AG
Date: 26-12-2020
Abstract: Tomatoes are consumed worldwide as fresh vegetables because of their high contents of essential nutrients and antioxidant-rich phytochemicals. Tomatoes contain minerals, vitamins, proteins, essential amino acids (leucine, threonine, valine, histidine, lysine, arginine), monounsaturated fatty acids (linoleic and linolenic acids), carotenoids (lycopene and β-carotenoids) and phytosterols (β-sitosterol, c esterol and stigmasterol). Lycopene is the main dietary carotenoid in tomato and tomato-based food products and lycopene consumption by humans has been reported to protect against cancer, cardiovascular diseases, cognitive function and osteoporosis. Among the phenolic compounds present in tomato, quercetin, kaempferol, naringenin, caffeic acid and lutein are the most common. Many of these compounds have antioxidant activities and are effective in protecting the human body against various oxidative stress-related diseases. Dietary tomatoes increase the body’s level of antioxidants, trapping reactive oxygen species and reducing oxidative damage to important biomolecules such as membrane lipids, enzymatic proteins and DNA, thereby ameliorating oxidative stress. We reviewed the nutritional and phytochemical compositions of tomatoes. In addition, the impacts of the constituents on human health, particularly in ameliorating some degenerative diseases, are also discussed.
Publisher: Wiley
Date: 17-11-2022
Abstract: Accurate identification of malignant lung lesions is a prerequisite for rational clinical management to reduce morbidity and mortality of lung cancer. However, classification of lung nodules into malignant and benign cases is difficult as they show similar features in computer tomography and sometimes positron emission tomography imaging, making invasive tissue biopsies necessary. To address the challenges in evaluating indeterminate nodules, the authors investigate the molecular profiles of small extracellular vesicles (sEVs) in differentiating malignant and benign lung nodules via a liquid biopsy‐based approach. Aiming to characterize phenotypes between malignant and benign groups, they develop a single‐molecule‐resolution‐digital‐sEV‐counting‐detection (DECODE) chip that interrogates three lung‐cancer‐associated sEV biomarkers and a generic sEV biomarker to create sEV molecular profiles. DECODE capturessEVs on a nanostructured pillar chip, confines in idual sEVs, and profiles sEV biomarker expression through surface‐enhanced Raman scattering barcodes. The author utilize DECODE to generate a digitally acquired sEV molecular profiles in a cohort of 33 people, including patients with malignant and benign lung nodules, and healthy in iduals. Significantly, DECODE reveals sEV‐specific molecular profiles that allow the separation of malignant from benign (area under the curve, AUC = 0.85), which is promising for non‐invasive characterisation of lung nodules found in lung cancer screening and warrants further clinincal validaiton with larger cohorts.
Publisher: American Chemical Society (ACS)
Date: 11-07-2019
DOI: 10.1021/ACS.ACCOUNTS.9B00192
Abstract: Historically, cancer was seen and treated as a single disease. Over the years, this image has shifted, and it is now generally accepted that cancer is a complex and dynamic disease that engages multiple progression pathways in each patient. The shift from treating cancer as single disease to tailoring the therapy based on the in idual's characteristic cancer profile promises to improve the clinical outcome and has also given rise to the field of personalized cancer treatment. To advise a suitable therapy plan and adjust personalized treatment, a reliable and fast diagnostic strategy is required. The advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems that show high potential for use in personalized cancer treatment. These devices require only minute s le volumes and have the capability to create instant cancer snapshots that could be used as tool for cancer risk indication, early detection, tumor classification, and recurrence. Miniaturized systems can combine a whole s le-to-answer workflow including s le handling, preparation, analysis, and detection. As such, this concept is also often referred to as "lab-on-a-chip". An inherit challenge of monitoring personalized cancer treatment using miniaturized systems is that cancer biomarkers are often only detectable at trace concentrations present in a complex biological s le rich in interfering molecules, necessitating highly specific and sensitive biosensing strategies. To address the need for trace level detection, highly sensitive fluorescence, absorbance, surface-enhanced Raman spectroscopy (SERS), electrochemical, mass spectrometric, and chemiluminescence approaches were developed. To reduce s le matrix interferences, ingenious device modifications including coatings and nanoscopic fluid flow manipulation have been developed. Of the latter, our group has exploited the use of alternating current electrohydrodynamic (ac-EHD) fluid flows as an efficient strategy to reduce nonspecific nontarget biosensor binding and speed-up assay times. ac-EHD provides fluid motion induced by an electric field with the ability to generate surface shear forces in nanometer distance to the biosensing surface (known as nanoshearing phenomenon). This is ideally suited to increase the collision frequency of cancer biomarkers with the biosensing surface and shear off nontarget molecules thereby minimizing nonspecific binding. In this Account, we review recent advancements in miniaturized diagnostic system development with potential use in personalized cancer treatment and monitoring. We focus on integrated microfluidic structures for controlled s le flow manipulation followed by on-device biomarker interrogation. We further highlight the progress in our group, emphasis fundamentals and applications of ac-EHD-enhanced miniaturized systems, and outline promising detection concepts for comprehensive cancer biomarker profiling. The advances are discussed based on the type of cancer biomarkers and cover circulating tumor cells, proteins, extracellular vesicles, and nucleic acids. The potential of miniaturized diagnostic systems for personalized cancer treatment and monitoring is underlined with representative ex les including device illustrations. In the final section, we critically discuss the future of personalized diagnostics and what challenges should be addressed to make these devices clinically translatable.
Publisher: American Chemical Society (ACS)
Date: 30-10-2013
Publisher: American Chemical Society (ACS)
Date: 15-07-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NH00258E
Abstract: Methylation dependent gold adsorption behaviour of extracellular vesicular DNA enables liquid biopsy test for cancer.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.BIOS.2019.02.028
Abstract: Surface-enhanced Raman scattering (SERS) based DNA biosensors have considered as excellent, fast and ultrasensitive sensing technique which relies on the fingerprinting ability to produce molecule specific distinct spectra. Unlike conventional fluorescence based strategies SERS provides narrow spectral bandwidths, fluorescence quenching and multiplexing ability, and fitting attribute with short length probe DNA sequences. Herein, we report a novel and PCR free SERS based DNA detection strategy involving dual platforms and short DNA probes for the detection of endangered species, Malayan box turtle (MBT) (Cuora amboinensis). In this biosensing feature, the detection is based on the covalent linking of the two platforms involving graphene oxide-gold nanoparticles (GO-AuNPs) functionalized with capture probe 1 and gold nanoparticles (AuNPs) modified with capture probe 2 and Raman dye (Cy3) via hybridization with the corresponding target sequences. Coupling of the two platforms generates locally enhanced electromagnetic field 'hot spot', formed at the junctions and interstitial crevices of the nanostructures and consequently provide significant lification of the SERS signal. Therefore, employing the two SERS active substrates and short-length probe DNA sequences, we have managed to improve the sensitivity of the biosensors to achieve a lowest limit of detection (LOD) as low as 10 fM. Furthermore, the fabricated biosensor exhibited sensitivity even for single nucleotide base-mismatch in the target DNA as well as showed excellent performance to discriminate closely related six non-target DNA sequences. Although the developed SERS biosensor would be an attractive platform for the authentication of MBT from erse s les including forensic and/or archaeological specimens, it could have universal application for detecting gene specific biomarkers for many diseases including cancer.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0RA05032F
Abstract: The detection of circulating biomarkers in liquid biopsies has the potential to provide a non-invasive route for earlier cancer diagnosis and treatment management.
Location: Australia
Location: Bangladesh
Start Date: 2021
End Date: 12-2023
Amount: $340,057.00
Funder: Australian Research Council
View Funded Activity