BioMEMS Research

Microfabricated devices for biological applications (e.g., gene arrays and lab-on-a-chip) have become quitecommon, giving rise to useful tools for discovery and diagnosis. Our current efforts focus on thedevelopment of a new generation of microdevices that incorporate living cells. This research effort isfueled by recent advances in the understanding of cellular behavior in microenvironments, and the need for new, more sophisticated devices for discovery, diagnosis, treatment, and high-throughput drug testing.

Projects

Our current BioMEMS projects include:

1. blood-on-a-chip
2. microreactors for viral production
3. dynamic tissue microsystems
4. chemotaxis-on-a-chip
5. the living cell microarray

Brief representative descriptions are provided below.

Blood-On-A-Chip: We are designing and microfabricating integrated modules for depleting red blood cells and platelet populations, sorting leukocytes into homogenous phenotypes, and interrogating cells based on phenotypic and genotypic characteristics for applications in infectious diseases, trauma, and immunoinflammatory processes. Blood cells represent a wealth of information pertaining to diseases,infections, malignancies or allergic conditions. However, extracting unaltered and accurate information depends not only on sophisticated genomic and proteomic instrumentation, but can be seriously biased by improper blood handling and preparation procedures. We are building an integrated platform to automatically and systematically handle blood while avoiding artifacts, and extract scientific or clinically relevant information from target populations of cells in blood. Individual modules are being developed for depleting red blood cells, sorting leukocytes into homogenous phenotypes and interrogating cells based on phenotypic or genotypic characteristics. Integrated microsystems for rapid and comprehensive blood analysis are poised to become single use, disposable, point-of-care diagnostic tools for clinical applications or science research tools for blood analysis from small laboratory animals.

Living Cell Array: The Living Cell Array (LCA) consists of an arrangement of 500x800mm cell culture chambers and microfluidic channels that deliver nutrients, stimulate the cells and remove the waste.Through proper design of the microfluidic network several concentrations of the stimulus are generated by continuous-flow diffusive mixing of adjacent laminar flow streams and delivered to the cells. Gene expression dynamics are monitored in the LCA device by profiling the induction of specific transcription factors in reporter cells and comparing the results to standard tissue culture formats. We have been able to extend this platform to accommodate many reporters on a single device to profile the dynamics (~5000 single time point measurements in one day) of multiple pathways in hepatocytes during inflammatoryresponses.

Dynamic Tissue Systems: We are also developing a novel, microfabricated in vitro system that mimics the in vivo organization of the liver acinus to study the dynamic sequence of expression of pro- and anti-inflammatory mediators induced after ischemia-reperfusion injury. Elements of this model include the Living Cell Array (LCA) and the development of liver sinusoid models using novel microfabrication techniques for controlling cell-cell interactions, and extracellular matrix and/or biocompatible polyelectrolytes for building multilayered cellular architectures.