Many perturbations in cellular physiology, particularly at the genomic and proteomic levels, are transient in nature and thus frequently overlooked by traditional molecular techniques. The overarching theme in this group is to develop miniaturized platforms to modulate and monitor cell and tissue behavior in the context of normal and pathological states. We complement this empirical approach with mathematical models to develop functions that correlate stimulus patterns to cell/tissue response. We have invested significant effort in the development of tools to enable real-time monitoring of intracellular phenomena in mono- or multi-cellular systems. Specifically, we have engineered a large library of reporter cell lines, which act as living reagents to monitor critical components of the cellular transcriptional network and other cell signaling pathways. By culturing these reporters in microfabricated arrays, we have produced "Living Cell Arrays" that enable us to exert exquisite control over the cellular microenvironment while characterizing complex cellular responses in real-time. Another thrust of this group is to develop dynamic tissue systems, in which compartments containing complete tissue constructs (either synthetic or tissue slices), are connected via microcahnnels in order to allow in vivo-like communication. Finally, various projects are ongoing in which nanoparticles are being used for diagnosis and therapy.

Examples of ongoing projects include:

• Continuous-flow microfluidic device for real-time detection of cellular secretions
• Microfluidic platforms to study heterotypic cell interactions that mediate inflammatory and metabolic processes on a cellular level
• Rapid analysis of cell secretions and rare surface proteins in microdroplets on a single-cell level
• High-sensitivity nanostructured metal electrodes for neural electrophysiology applications
• Microplatforms for studying communication between organotypic brain slices in the context of epilepsy (Brain-on-a-chip)
• Allergy-on-a-Chip: a microdevice for assessing chemical sensitization
• Efficient viral and non-viral protein and oligonucleotide delivery to cells
• Microfluidic system for detection of autoantibodies for early diagnosis of diabetes

Representative Publications:

• Koria P, Yagi H, Megeed Z, Nahmias Y, Sheridan R, Yarmush ML. Self assembling elastin-growth factor chimeric nanoparticles for the treatment of chronic wounds. Proc Nat’l Acad Sci 2011; 108: 1034-9
• Konry T, Dominguez-Villar M, Baecher-Allan C, Hafler DA, Yarmush ML. Droplet-based microfluidic platforms for single T cell secretion analysis of IL-10 cytokine. Biosensors and Bioelectronics 2011; 26: 2707.
• Konry T, Smolina I, Yarmush JM, Irimia D, Yarmush ML. Ultrasensitive Detection of Low-Abundance Surface-Marker Protein Using Isothermal Rolling Circle Amplification in a Microfluidic Nanoliter Platform. Small 2011; 7: 395.

• Seker E, Berdichevsky Y, Begley M, Reed ML, Staley KJ, Yarmush ML. The fabrication of low-impedance nanoporous gold multiple-electrode arrays for neural electrophysiology studies Nanotechnology 2010; 12: 125504.
• Berdichevsky Y, Staley KJ, Yarmush ML. Building and manipulating neural pathways with microfluidics. Lab on a Chip 2010; 10: 999.
• Patel S, King KR, Yarmush ML. DNA-triggered innate immune responses are propagated by gap junction communication. Proc Nat’l Acad Sci 2009; 106: 12867-72.
• Roach KL, King KR, Uygun Basak, Kohane IS, Yarmush ML, Toner M. High throughput single cell bioinformatics. Biotechnol Prog 2009; 25: 1772-1779.
• Yarmush ML, King KR.  Living Cell Microarrays. Annual Rev Biomed Eng2009; 11: 235.
• King KR, Wang S, Jayaraman A, Yarmush ML, Toner M. Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments. Lab on a Chip 2008; 8: 107.
• King KR, Wang, S, Irimia D, JayaramanA, TonerM, Yarmush ML. A high-throughput microfluidic real-time gene expression living cell array.  Lab on a Chip 2007; 7: 77.