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. Silicon-based integrated circuit technology that has revolutionized computing and communication, can become a platform to realize these complex sensing systems, but a new design methodology needs to be considered to allow close interface with biosensing platforms with CMOS chips. In this project, we have shown multiple methodologies that address this very point.

In this first work, we demonstrated a crosscut approach to allow seamless microfluidic interface with CMOS based sensor array for high precision detection of magnetically label sensor cells. We proposed a signal processing based approach that allows multiple site detection with exponentially low false positive rates. Through this computational based approach, we leverage the ability to explore  signal processing algorithms for massively multiplexed rapid cell tracking and cell detection.

In a follow up work, we demonstrate, for the first time, a CMOS microfluidic system that is capable of 1) pumping bulk electrolyte flow with AC electroosmosis, 2) cell manipulation and separation with dielectrophoresis (DEP), 3) label-free bio-molecular and cell sensing, classification with dedicated 16-element impedance spectroscopy receivers. While we demonstrate these kernel functionalities in a multi-chip module/microfluidic interface, the overall architecture, fluidics and sensing components can be massively scaled up and customized for various POC applications due to complete elimination of pressure-driven flows. We also extended the concept of impedance spectroscopy to smart wound healing. Chronic wounds are  major health concern affecting more than 25 million people in USA. In this work, we present a CMOS (complementary-metal-oxide-semiconductor)-chip/nanowell based hybrid smart bandage interface that allows in-situ real-time and long-term label-free quantification of cytokine release from skin directly on complex wound fluids. These papers have been presented in flagship conferences and journals and appreciated by the leading researchers in the community.

The project has been involved multiple graduate students, and undergraduate students over the years. All the students have been trained in the multiple areas that span chip design, bio-sensing, signal processing, and testing coupled in a very multi-disciplinary program. We expect the research results from this project to have a major impact in a broader domain of science and technology, in enabling new sensing, imaging and communication platforms and capabilities.

Last Modified: 02/28/2022
Modified by: Kaushik Sengupta