CMOS-Driven Pneumatic-Free Scalable Microfluidics and Fluid Processing with Label-Free Cellular and Bio-Molecular Sensing Capability for an End-to-End Point-of-Care System

Abstract

The emergence of the pandemic has demonstrated the necessity of point-of-care (POC) molecular diagnostic platforms that encompass an end-to-end system (from sample fluid to diagnostic information) with the ability to allow rapid analysis on the spot. While POC sensing technologies have been demonstrated in miniaturize chip-scale platforms [1–5], the bottlenecks in enabling end-to-end low-cost handheld platforms have often been bio-sample handling, filtering, mixing with re-agents that are critical to the robustness of the assay chemistry and sensing sensitivity/specificity. These processes are typically carried out either manually or by employing complex pneumatic flow control with multiple bulky syringe pumps, which have been a severe limitation to enable end-to-end biosensing systems (Fig. 18.2.1). While electrically driven droplets, molecular and cell manipulation techniques, such as electro-wetting, electrophoresis and dielectrophoresis, have been demonstrated in singular systems before [1], they do not have the ability to process bulk bio-sample fluids that is required for POC devices. In this paper, we present a scalable approach that merges the functionalities of sample processing and cellular/bio-molecular sensing in a single system and eliminates any pneumatic pumping mechanisms by exploiting CMOS-based electrically driven electro-kinetic flow of bulk fluids. We demonstrate, for the first time, a CMOS-microfluidic system that is capable of 1) pumping bulk electrolyte fluid with AC electro-osmosis, 2) cell manipulation and separation with dielectrophoresis (DEP), 3) label-free biomolecular and cell sensing, classification with dedicated 16-element impedance spectroscopy receivers. While we demonstrate these kernel functionalities in a multichip module/microfluidic interface (Fig. 18.2.1), the overall architecture, fluidics and sensing components can be massively scaled up for various POC applications due to elimination of pressure-driven flows (Fig. 18.2.1).