Research

 

Single Cell

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No two cells are identical with each other because of cellular heterogeneity. In order to understand the cell-to-cell variation, we develop droplet-based single-cell assay platform where individual cells are encapsulated into isolated water-in-oil droplets. With the developed microfluidic platform, we could study proteolytic activity of single cancer cells and have a better understanding of cancer progression.

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Single cell multiplexed proteolytic assay in droplet microfluidics. (a) Proteases produced within cell-encapsulated droplets cleave multi-color FRET substrates to yield multiple fluorescent signals. (b) Individual cells and FRET substrates are encapsulated in single droplets through microfluidics. (c) Four different signals from FRET-substrate sensors with different excitation and emission wavelengths can be observed simultaneously in individual droplets.

 

Soft Materials

Rongcong-AFM1

Intelligent soft materials have gained increasing interest due to their ability to dynamically respond to external stimuli and convert them into user-defined functionalities. We developed stimuli-responsive soft hydrogels as microfluidic components, flexible actuators, drug carriers and soft robotics.

BioAssay

Miles_Chia_JACSCoverDraft

Our research work in bioassay development focuses centrally on a new highly integrative approach that combines microfluidics with computational analysis to study proteolytic activities, particularly within the Matrix Metalloproteinase (MMP) and A Disintegrin and Metalloproteinase (ADAM) enzyme families.  These enzymes often become dysregulated in diseases such as cancer and endometriosis, where they principally mediate extracellular matrix degradation and cellular invasion. Although metalloproteinases have been extensively studied for decades, clinical trials targeting them have largely failed in part due to a poor understanding of the complex web of interactions in which they participate. Diverse repertoires of substrates, extensive post-translational regulation, and complex feedback mechanisms have frustrated efforts to understand metalloproteinase biology in the context of a broader network of biochemical interactions.

Although the measurements of protease activities are critical to study the disease model systematically, no current method satisfactorily enables efficient multi-variate study of proteases in a direct, quantitative, specific, multiplexed manner, particularly in sample-limited applications including those utilizing primary clinical samples.  We address this need by integrating a microfluidic droplet-generator, a picoinjector, and the computational approach Proteolytic Activity Matrix Analysis (PrAMA) to infer specific protease activities from an array of droplet-based kinetic measurements using FRET-based synthetic protease substrates.  With minimal sample volumes (<20uL), our approach allows for the rapid assessment of multiple metalloproteinase activities in complex biological samples by automatically and simultaneous monitoring up to hundreds of droplet reactions containing distinct biochemical reagents for determining multiple specific enzymatic activities.

 

Integrative Devices

Biosensor

By incorporating microfluidic platform, single cell analysis, ion concentration polarisation etc, we try to develop integrated biosensors for biomedical applications including POC and disease diagnosis.