Lab-on-a-chip systems for blood cell separation, counting, and characterization

Blood cell differential counting provides valuable information about human health and thus is essential for both medical diagnostics and scientific research. There is continuous demand for miniaturization of blood analysis system for real-time monitoring astronauts' health in spaceflight and for performing point-of-care diagnosis. Lab-on-a-chip (LOC) or micro total analysis system (muTAS) has opened new opportunities to achieve accurate, fast, and affordable blood analysis with minute sample consumption. In this work, LOC system has been designed, fabricated and tested for separating, counting, and characterizing blood cells with the aim of developing highly integrated blood cell analysis device. Deterministic lateral displacement principle which utilizes the asymmetric bifurcation of laminar flow around obstacles has been explored to successfully separate three major blood cells based on size differences. Microfabricated Coulter counter with dielectrophoretic focusing was able to count blood cells by impedance pulses with magnitudes proportional to their volumes. High counting ability was achieved with a differential measurement scheme and effective signal processing electronics. A microelectrode array in combination of a novel cell patterning method has been developed to characterize cell dielectric properties on the single-cell basis. Two issues related to impedance sensing at the microscale, the electrode polarization and the current leakage, have been successfully addressed by in situ polymerization of a conductive polymer on the microelectrodes and by using low conductive isotonic medium respectively. Two subtypes of lymphocytes were discriminated from each other by their impedance spectra. Best fitting parameters of each type of cells were derived using an equivalent circuit model and showed good agreement with published results obtained by AC electrokinetic method. Such method enables fast single-cell dielectric property characterization and can guide the design of an efficient cell counting system to differentiate white blood subtypes by their intrinsic dielectric parameter differences. It is possible to integrate these basic functions into a single chip which can be easily operated and provide accurate blood cell differential counting results with fast speed using a very small amount of blood sample.