Grant: Research Tools and Instruments - Category 1 (<$150,000)

Fast, efficient isolation of specific phenotypes of cells from heterogeneous mixtures, such as blood, is important in many areas of biological and health sciences. Frequently, the desired cell types, such as Mesnchymal stem cells and circulating tumor cells, are extremely rare, with fractions ranging from 1:105 to 1:1011 compared to the main population. Recent work in microfluidic cell separation has demonstrated size-based separation at low flow rates, but has a tendency to be clogged at higher flow rates. The fundamental limitation of these current mechanisms is their ability to process vast quantities of cells while remaining selective enough to isolate specific rare cell types. The proposed RTI grant will support a research program to separate cells by their mechanical deformability, which prior AFM studies have shown to significantly vary across difference cell types. Using a new approach to actively deform cells in flow, this separation mechanism is capable of processing vast quantities of cells at high flow rates without clogging. Equipment requested by this grant will specifically enable new capabilities in high speed microscopy and imaging, microfabrication via soft lithography, as well as testing and instrumentation of microfluidic devices. By leveraging microfabrication of structures at the size scale of individual cells, with instrumentation techniques to mechanically deform structures with nanometer precision, as well as, precise control of flow in using the tools of multilayer soft lithography, this research program aims to create a 'deformability spectrometer' for cells. The requested equipment will also support several related research programs including: impedance spectroscopy flow cytometry, particle deposition in microfluidic environments, thermally actuated microfluidic relay valves, and MEMS-based drug delivery devices.