CMOS-Based Electrokinetic Microfluidics With Multi-Modal Cellular and Bio-Molecular Sensing for End-to-End Point-of-Care System.

The importance of point-of-care (POC) bio-molecular diagnostics capable of rapid analysis has become abundantly evident after the outbreak of the Covid-19 pandemic. While sensing interfaces for both protein and nucleic-acid based assays have been demonstrated with chip-scale systems, sample preparation in compact form factor has often been a major bottleneck in enabling end-to-end POC diagnostics. Miniaturization of an end-to-end system requires addressing the front-end sample processing, without which, the goal for low-cost POC diagnostics remain elusive. In this paper, we address bulk fluid processing with AC-osmotic based electrokinetic fluid flows that can be fully controlled, processed and automated by CMOS ICs, fabricated in TSMC 65 nm LP process. Here, we combine bulk fluid flow control with bio-molecular sensing, cell manipulation, cytometry, and separation-all of which are controlled with silicon chips for an all-in-one bio-sensing device. We show CMOS controlled pneumatic-free bulk fluid flow with fluid velocities reaching up to 160 μm/s within a microfluidic channel of 100 × 50 μm 2 of cross-sectional area. We incorporate electrode arrays to allow precise control and focused cell flows ( ±2 μm precision) for robust cytometry, and for subsequent separation. We also incorporate a 16-element impedance spectroscopy receiver array for cell and label-free protein sensing. The massive scalability of CMOS-driven microfluidics, manipulation, and sensing can lead to a new design space and a new class of miniaturized sensing technologies.