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BioSystems and Micromechanics (BioSyM) IRG

Lead PI: Professor Roger D. Kamm
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The SMART BioSyM IRG has three major areas of focus. First and foremost is the development of new technologies to address critical medical and biological questions applicable to a variety of diseases but focusing on liver disease. Second, is the further development of these technologies to provide novel solutions for the healthcare industry. Third, is to provide a constant source of new technologies to the broader Singapore research infrastructure.

  
BioSyM

Mission
Our mission is to develop the fundamental science and technologies that will enable the discoveries that will revolutionize medicine.

Major Objectives
The guiding tenet of BioSyM is that accelerated progress in biology and medicine will critically depend upon the development of modern analytical methods and tools that will provide a deep understanding of disease at the molecular, cellular and organ levels.

RESEARCH AREAS AND PROJECTS

Single Molecule Sensors and Sequence Identification

DNA Micromechanics
Develop nanofluidic devices for the manipulation and mapping of single DNA molecules. Interface optical and magnetic tweezers with fluidic devices to interrogate DNA-protein interactions.

Analysis of Active Proteases in Inflammation
Biotin-linked probes will be designed to capture active forms of serine-, cysteine-, and metallo-proteases. Analysis of the probes will be by Avidin binding and release for both gel electrophoresis and mass spectrometry.

Single-Molecule Binding and Force Spectroscopy
Single proteins can be manipulated using an optical trap, and their force-extension relationships measured. By careful analysis of these measurements, information on protein conformation and complex formation will be obtained.

Micro/Nanofluidic and Optical Profiling of Cells and Molecules

Continuous, high-throughput sorting of malaria-infected RBC
Develop a microfluidic cell sorting device to be applied for sorting rare, infected or diseased cells from a larger population. This could lead to more accurate diagnostics in rural, resource-limited settings, as well as scientific advances in studying these diseases.

A flow-through assay for tumor cell extravasation
It is now possible to separate rare circulating tumor cells from a cancer patient. Methods are being developed to simulate the process by which these cells adhere to the vascular wall, and migrate into tissue in order to test new anti-metastatic drugs.

Multi-Scale Image Informatics Investigation of Fibrotic Diseases

Studying liver fibrosis based on high throughput, high content Image cytometry
The goal of this project is to understand the molecular factors that induce the activation of hepatic stellate cells in three-dimensional tissue constructs and in animal models.

Applications to other fibrotic diseases
These same methods are being applied to a variety of other diseases that invoke fibrotic tissue growth such as pulmonary fibrosis and scarring.

Control of Cell Population Behavior in Tissue Constructs Using Image Analysis and Stochastic Modeling

Creation of Organ Mimics for Drug Testing and Toxicity Screens
A need exists to create experimental platforms that recapitulate certain aspects of organ function, for the purpose of drug testing and toxicity screens. Microfluidic systems are being developed that incorporate multiple cell types and can be used in high throughput screening.

Stochastic Modeling of Cell Population Behaviors
Cells are modeled as stochastic agents reacting to biochemical and biomechanical cues. Collective behaviors emerging from cell-cell interactions as well as from cell-matrix interactions are predicted through computer simulation.

Microfluidic Experiment and Identification
Stochastic cell population models are identified through microfluidic experiments. Three-dimensional images using a confocal microscope are revealing cell sprouting and growth processes. Effective identification methods are developed to capture complex stochastic behaviors of the cell population.

Model-Based Stochastic Feedback Control
The microfluidic bioreactor is instrumented for real-time feedback control of cell population growth experiments. Based on the stochastic cell population models, an optimal sequence of control inputs is computed in real time, guiding the cell population towards a desired morphological formation.

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