The use of electrochemical impedance spectroscopy (EIS) to carry out real-time observations of cells and extract information about their physiological properties has expanded in recent years. The ease of integrating EIS with microfluidic devices has allowed the technology to further expand into biomedical research. We have developed a 64X64 sensing array, with 10μm pixels in 180nm CMOS, that supports switching frequencies up to 100MHz.
Market Opportunity
Capacitive sensing and EIS are appealing technologies for miniaturized and integrated biochemical and cellular measurement systems because of their low cost and ease of use. Unfortunately, they often have low dynamic range and low chemical specificity. CMOS-compatible ion-sensitive field effect transistors (ISFETs) can scale up to large, dense arrays, enabling high-throughput DNA sequencing and assays, cellular metabolism sensing, chemical imaging, and food safety screening, but drift and flicker noise make longer applications such as cell-culture monitoring challenging for ISFETs.
Innovation and Meaningful Advantages
Our innovative 64X64 sensing array, with 10μm pixels in 180nm CMOS, supports switching frequencies up to 100 MHz. The array features code-division multiplexed readout of all 64 rows simultaneously, offering opportunities for extended integration times, higher frame rates, improved common-mode rejection, and new wide-bandwidth sensing modalities. In addition to traditional row-scanned image-acquisition, our sensor array can acquire data through code division multiplexing (CDM), which records all rows using orthogonal spreading codes. CDM offers extended integration times, faster frame rates, and improved rejection of parasitic capacitances within the array.
The CMOS sensor array includes an active sensing area of pixels arranged in an array with a pitch, each pixel having an exposed surface electrode alongside switches and logic gates, as well as non-overlapping clocks configured to rapidly charge and discharge the exposed surface electrode. This allows control signals to steer a switched output current between shared column outputs.
Our novel in-pixel chopping method simultaneously reduces the drift and l/f noise of CMOS-integrated titanium nitride (TiN) ISFETs. It has long been understood that metal-oxide-semiconductor field-effect transistor (MOSFET) noise can be reduced by cycling between accumulation and inversion. However, directly chopping the solution potential at high frequencies is impractical. Our ISFET switching scheme modulates the source and the drain voltages instead of the chemical gate. In addition to lowering l/f noise, cycling Vgs helps to reduce the mean electric field at the electrode, supporting slower ion crossing rates and reducing drift.
This integrated electrochemical imaging has the potential to contribute to medical diagnostics and environmental monitoring, as well as discoveries of new microbial populations.
Collaboration Opportunity
We are interested in exploring 1) startup opportunities with investors in the diagnostic or medical imaging space; 2) research collaborations with leading diagnostic or medical imaging companies to develop this technology; and 3) licensing opportunities with diagnostic or medical imaging companies.
Principal Investigator
Jacob Rosenstein, PhD
Associate Professor of Engineering
Brown University
IP Information
US Application US 2022-0214304 A1, Published July 7, 2022
Publications
Hu K, Arcadia CE, Rosenstein JK. A Large-Scale Multimodal CMOS Biosensor Array With 131,072 Pixels and Code-Division Multiplexed Readout. IEEE Solid-State Circuits Letters 2021 Feb 3;4:48-51. doi: 10.1109/LSSC.2021.3056515.
Arcadia CE, Hu K, Epstein S, Wanunu M, A. Adler A, J. K. Rosenstein JK. CMOS Electrochemical Imaging Arrays for the Detection and Classification of Microorganisms. 2021 IEEE International Symposium on Circuits and Systems (ISCAS):1-5. doi: 10.1109/ISCAS51556.2021.9401471.