Thrust 1 focuses on developing micro/nanoscale tools to probe fundamentals of molecular interactions under dynamic constraints, and to study how phenomena such as molecular crowding affects cellular processes. Successful development of our approach – quantitative sensing of kinetic interactions among intra- and extracellular proteins and proteolytic enzymes – will be critical to the identification of drug targets that are implicated in cell/tissue disease or that significantly affect cell migration and tissue degeneration rates. The experimental and modeling capabilities explored herein will serve as the basis for a new class of mechano-diagnostic sensors.

Thrust 2 is organized around the unifying theme of multiplexed functional cytometry to study heterogeneous cell populations. Here, we are expanding the horizon of microfluidic cell characterization, biophysical characterization of cells and subcellular structures, and of multiwell cell culture analysis to various cell functional modalities, thereby aiming to resolve the critical technical bottlenecks of understanding complex cell systems.

Thrust 3 focuses on understanding of emergent behaviours of cell clusters in-vitro through analysis based on integrated nano / microscale optical, microfluidics and mechanical experiments and modelling. Our aim is to exploit such understanding for drug screening / development, regenerative medicine, and cancer treatment.

Thrust 4 represents our explicit recognition of the need for our work to move toward in vivo applications. Current focus is on developing a range of imaging technologies. Several breakthrough imaging technologies are at various stages of development in BioSyM. Multi-plexed volume holography methods are under development that will apply rapid, intrinsically three-dimensional capabilities to biological imaging. In separate studies, a new index for liver fibrogenesis, Fibro-C, has been developed that enhances the diagnostic capabilities of standard histopathology. New methods are under study that would allow similar measures to be made in vivo, under minimally-invasive conditions.

Cutting across the thrusts, BioSyM is working on three Cross-Thrust Initiatives (CTIs) that focus on translational applications that bridge length scales. The goal of these CTIs is to further develop and deploy selected BioSyM technologies to answer pressing questions in biofilm control, stem and progenitor cell isolation, and metastatic cancer.