An optofluidic approach to miniature flow cytometry

Summary form only given. Flow cytometry is a powerful high-throughput single-cell characterization tool that has significant impact on both biomedical research and clinical diagnostics. In flow cytometry, the analysis is performed by passing a narrow stream of cells through a focused laser beam at a rate of thousands of cells per second. Information regarding the size, type, and contents of cells can be subsequently derived through the analyses of the excited fluorescence emission or scattered light arising from each individual cell. In the past decade, flow cytometry has undergone remarkable advancements. It offers reliable, high-throughput, high-accuracy single-cell analyses for a wide variety of biomedical studies. It has also quickly become the method of choice for many clinical diagnostics, ranging from routine blood tests to diagnoses of lethal diseases such as leukemia and HIV. However, as of now the full potential of flow cytometry as a clinical diagnostic tool has yet to be realized. Its high cost (generally >; $100,000), mechanical complexity, bulky size, and need for highly trained personnel have limited its usage. Therefore there is an incentive to develop affordable, highly integrated, miniaturized flow cytometry systems. Recently we have pioneered several novel on-chip flow and light manipulation techniques which could lead to the development of compact, inexpensive, and fully functionalized on-chip flow cytometry. Specifically these techniques include "microfluidic drifting"-based three-dimensional (3D) hydrodynamic focusing of fluids, tunable optofluidic cylindrical microlenses for light focusing in the X-Z chip plane, and tunable liquid gradient refractive index lens (L-GRIN) for focusing light in the X-Y plane. By integrating these newly developed/proposed fluidic and optical microcomponents, we have developed a fully-integrated microfluidic flow cytometry chip that is capable of high-throughput, multi-parametric cell analysis. The chip includ- s a fluidic component a three dimensional (3D) hydrodynamic cell focusing module based on the "microfluidic drifting" technique, and a series of integrated optical fibers to allow the coupling of laser detection light and on-chip detection of various optical signals such as forward scattering (FSC), side scattering (SSC), and fluorescence (FL). The successful integration of cell focusing and multi-parametric optical detection components in a mass-producible microfluidic device has made it possible for a low-cost flow cytometry chip suitable for point-of-care clinical diagnosis. This flow cytometry chip can also serve for the purpose for "decentralizing" the flow cytometry applications and make affordable flow cytometry analysis available to individual research laboratories.