Hydrodynamic focusing for impedance-based detection of specifically bound microparticles and cells: Implications of fluid dynamics on tunable sensitivity

A 4-electrode impedance-based microfluidic sensor was designed to achieve tunable sensitivity, while simultaneously decreasing the channel clogging and nonspecific binding that often adversely impact device function. Hydrodynamic focusing – a characteristic of laminar flow at low Reynoldʹs number – provides highly controllable sensitivity in impedance-based microfluidic biosensors, by creating a “virtual” microchannel with soft walls and adjustable dimensions. Enhanced sensitivity, limited nonspecific binding, and a reduction in microchannel clogging have been achieved using hydrodynamic focusing within a 250 μm deep by 1 mm wide microchannel. The microfluidic sensor was able to detect microparticles as small as 5 μm in diameter specifically bound between co-planar platinum micro-electrodes. However, detection of submicron particles and E. coli cells in similar fashion proved to be challenging. A theoretical analysis of forces exerted by the fluids within the microchannel allowed specification of flow rates amenable to decreased nonspecific binding of interfering cells or microparticles, while ensuring minimal disruption to specifically bound targets. Simulations revealed that complex flow behavior of the hydrodynamically focused streams around specifically bound micron-sized particles reduces sensitivity. An improved understanding is thus presented of the parameters that impact the sensitivity of impedance-based biosensors implementing hydrodynamic focusing and specific target binding.