A5039683697- Single-cell and spatial transcriptomics
- Microfluidic and Capillary Electrophoresis Applications
- Biosensors and Analytical Detection
- Microfluidic and Bio-sensing Technologies
- Innovative Microfluidic and Catalytic Techniques Innovation
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Advanced MEMS and NEMS Technologies
- Advanced Biosensing Techniques and Applications
- T-cell and B-cell Immunology
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Electrowetting and Microfluidic Technologies
- Acoustic Wave Resonator Technologies
- Prenatal Screening and Diagnostics
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Atherosclerosis and Cardiovascular Diseases
- Molecular Communication and Nanonetworks
- Molecular Biology Techniques and Applications
National University of Singapore
2019-2024
Singapore-MIT Alliance for Research and Technology
2023-2024
Singapore Institute of Technology
2022
City University of Hong Kong
2022
National University Health System
2020
Institute of Molecular and Cell Biology
2013-2018
Agency for Science, Technology and Research
2008-2017
Institute of Molecular and Cell Biology
2017
National University System
2017
Massachusetts Institute of Technology
2007-2014
Abstract The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing 49,155 cells. identified a pervasive genetic and transcriptomic dichotomy malignant cells, distinct gene expression, DNA copy number regulatory network. recapitulated these subtypes in 3,614 patients. two intrinsic subtypes, iCMS2 iCMS3, refine CMS....
Fatal Chimeras Impaired DNA-methylation maintenance during early embryonic development may cause imprinting-related diseases. Lorthongpanich et al. (p. 1110 ) have devised a sensitive assay to probe multiple imprinted gene loci for their state at the single-cell level. Blastomeres with defective imprinting showed complex, epigenetic chimeras developed fatal defects. Pronuclear transfer restored normal mouse development, offering therapeutic strategy overcome defects caused by maternal...
The authors present microfluidic logic gates based on two-phase flows at low Reynold’s number. presence and the absence of a dispersed phase liquid (slug) in continuous represent 1 0, respectively. working principle these devices is change hydrodynamic resistance for channel containing droplets. Logical operations including AND, OR, NOT are demonstrated, may pave way microfludic system automation computation.
We developed a novel method to increase the sensitivity of standard enzyme-linked immunosorbent assay (ELISA) using multiplexed electrokinetic concentration chip. The poly(dimethylsiloxane) (PDMS) molecular concentrator(1) was used trap and collect charged fluorescent product target-bound enzyme turnover reaction ELISA that occurred in 96 well plate. Detection sensitivities both prostate specific antigen (PSA) CA 19-9 (a human pancreatic gastrointestinal cancer marker) ELISAs serum are...
A massively parallel nanofluidic concentration device array for multiplexed and high-throughput biomolecule detection is demonstrated. By optimizing the microchannel/nanojunction design channel conductivity, an of up to 128 devices were fabricated. Operation entire requires only one inlet outlet reservoir, with application a single operational voltage bias across them. Concentration efficiencies found be uniform within array, 5% error. Alternatively, speed in each can individually tuned by...
We describe an electrokinetic concentration-enhanced aptamer affinity probe electrophoresis assay to achieve highly sensitive and quantitative detection of protein targets in a microfluidic device. The key weaknesses as binding agent (weak strength/fast target dissociation) were counteracted by continuous injection fresh sample while band-broadening phenomena minimized due self-focusing effects. With 30 min signal enhancement, we can detect 4.4 pM human immunoglobulin E (IgE) 9...
Digital real-time PCR assay rapidly measures single telomere lengths and uncovers maintenance mechanisms in cancer.
Nanofluidic channels can be used to enhance surface binding reactions, since the target molecules are closely confined surfaces that coated with specific partners. Moreover, diffusion-limited significantly enhanced if steered into nanochannels via either pressure-driven or electrokinetic flow. By monitoring nanochannel impedance, which is sensitive binding, low analyte concentrations have been detected electrically in nanofluidic within response times of 1−2 h. This represents a ∼54 fold...
Electrokinetic preconcentration coupled with mobility shift assays can give rise to very high detection sensitivities. We describe a microfluidic device that utilizes this principle detect cellular kinase activities by simultaneously concentrating and separating substrate peptides different phosphorylation states. This platform is capable of reliably measuring single adherent cells cultured in nanoliter volume microwells. also novel method utilizing spacer significantly increase separation...
Abstract Human pancreatic islets containing insulin-secreting β-cells are notoriously heterogeneous in cell composition. Since β-cell failure is the root cause of diabetes, understanding this heterogeneity paramount importance. Recent reports have cataloged human islet transcriptome but not compared single detail. Here, we scrutinized ex vivo cells from healthy donors and show that they exhibit de-differentiation signatures. Using single-cell gene expression immunostaining analyses, found to...
In keeping with the rule of "form follows function", morphological aspects a cell can reflect its role. Here, it is shown that cellular granularity lymphocyte, represented by intrinsic side scatter (SSC), potent indicator state and function. The lymphocyte increases from naïve to terminal effector state. High-throughput cell-sorting yields SSC
Homogeneous assay platforms for measuring protein–ligand interactions are highly valued due to their potential high-throughput screening. However, the implementation of these multiplexed assays in conventional microplate formats is considerably expensive large amounts reagents required and need automation. We implemented a homogeneous fluorescence anisotropy-based binding an automated microfluidic chip simultaneously interrogate >2300 pairwise interactions. demonstrated utility this platform...
Quantitative nucleic acid amplification tests are of great importance for diagnostics, but current approaches require complex and costly optical setups that limit their nonlaboratory applications. Herein we describe the implementation a microfluidics platform can perform binary DNA-amplification-activated droplet sorting. The digital sort-enabled counting (DISCO) enables label-free absolute quantification acid. This is achieved by provoking pH change in droplets through loop-mediated...
A single-ended input to balanced output 425MHz mechanically coupled electromechanical filter is presented. This technology provides 1MHz channel select filtering while eliminating the need for RF switches and baluns in front-end transceivers. The achieves 8dB insertion loss with -50dB stop-band rejection -48dB common-mode suppression
Drop-PEARL enables rapid screening and isolation of virus-neutralizing antibody secreting cells for high-throughput therapeutic discovery.
We introduce a laser-patterned tape as master for replica moulding microfluidics in poly(dimethylsiloxane) (PDMS). Normally, laser is applied to scribe microchannels directly on poly(methyl methacrylate) (PMMA) substrates. This direct engraving usually offers faster turn-around time than conventional soft lithography but generates rough surfaces which perform poorly under phase-contrast microscopy imaging. Using the template replica-moulding PDMS, we combine rapid of ablation and relatively...
Enzymatic secretion of immune cells (leukocytes) plays a dominant role in host responses to myriad biological triggers, including infections, cancers, and cardiovascular diseases. Current tools probe these leukocytes inadequately profile vital biomarkers; the need for sample preprocessing steps cell lysis, labeling, washing, pipetting inevitably triggers cells, changes its basal state, dilutes individual bulk assays. Using fully integrated system multiplexed profiling native single-cell...
Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection many cancers. However, scaling such assays clinical translation impractical because the high cost whole-genome bisulfite sequencing. We show that small fraction GC-rich genome highly enriched in CpG sites disproportionately harbors most cancer-specific signature. Here, we report on simple effective heat enrichment CpG-rich regions sequencing (Heatrich-BS) platform allows...
Digital PCR (dPCR) is an important tool for precise nucleic acid quantification in clinical setting, but the limited multiplexing capability restricts its applications quantitative gene panel profiling. Here, this work describes melt-encoded-tags expanded optical readout digital (METEOR-dPCR), a simple two-step assay that enables simultaneous of large arbitrary genes dPCR platform. Target are quantitatively converted into DNA tags with unique melting temperatures through ligation approach....
5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the most abundant DNA modifications that have important roles in gene regulation. Detailed studies of these different epigenetic marks aimed at understanding their combined effects dynamic interconversion are, however, hampered by inability current methods to simultaneously measure both modifications, particularly samples with limited quantities. We present analysis restriction enzyme for simultaneous detection multiple epigenomic...