Integrated flow cytometer system on a chip platform

University Of California, San Diego, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): Flow cytometers are an indispensable biomedical tool that measures the angular scattering of light from a cell/sample and/or the fluorescence the cell/sample emits, creating the basis for routine blood counts, cancer screenings, and a wide range of other diagnostics and assays. Flow cytometers employ high-quality optical systems and complex electrical or mechanical cell sorting devices to enable sensitive, reproducible detection and sorting of cells, but these same systems make the instrument expensive to fabricate and maintain. The aim of the project is to create a low-cost, compact flow cytometer that can be widely available to clinicians and researchers. The system will also possess unique functionality unavailable by today's system. Plastic photonic circuits will be integrated with microfluidics and microacoustically actuated cell sorters on a microchip platform. This design readily allows the creation of a sorting scheme for the ordered removal of a small number of cells of interest, allowing researchers to remove the specific cells they are interested in for additional individual studies, such as the genotyping of individual cancer cells. Device design will be carried out based on combined results from optical and fluidic simulations performed for polymer-based structures. Over the course of three years, several device test and redesign cycles will be made possible by the rapid prototyping allowed by polymer replica molding and the use of off-the-shelf piezoelectric actuators, LED/diode laser sources, and Si photodetectors. Successful demonstration of the feasibility of this device will be measured by (1) the realization of a cell detection module capable of simultaneously detecting forward scatter, side scatter, and fluorescence from standard cytometry calibration polymer beads with sufficient sensitivity to yield a coefficient of variation with 11% of that measured by a commercial benchtop cytometer. (2) the development of a system prototype with capabilities sufficient for removal of a single cell from a high-throughput flow channel (i.e. up to 100,000 cells/min per channel, multiplied by the number of channels). (3) the ability to choose and remove individual cells in flow to a spatially-indexed sorting channel for further study (e.g. genotyping of single cancer cells). The development of an inexpensive, disposable chip-based flow cytometer would make the device more widely available from a financial standpoint to both clinicians and researchers alike, helping to lower net testing costs, contain biohazard materials, and provide a more rapid turnaround on results from the wide range of tests currently run on flow cytometers, such as routine clinical bloodwork, HIV and cancer progression monitoring, or research-based cell studies. In addition, the development of our proposed single-cell sorting capabilities would automate the isolation of individual cells of interest, making it an invaluable tool for facilitating biomedical breakthroughs in areas such as our understanding of cancer, where the ability to perform single-cell genotyping for studies of the evolution of cancers will be critical.