CoVSense: Ultrasensitive Nucleocapsid Antigen Immunosensor for Rapid Clinical Detection of Wildtype and Variant SARS-CoV-2.

The widespread accessibility of commercial/clinically-viable electrochemical diagnostic systems for rapid quantification of viral proteins demands translational/preclinical investigations. Here, Covid-Sense (CoVSense) antigen testing platform; an all-in-one electrochemical nano-immunosensor for sample-to-result, self-validated, and accurate quantification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N)-proteins in clinical examinations is developed. The platform's sensing strips benefit from a highly-sensitive, nanostructured surface, created through the incorporation of carboxyl-functionalized graphene nanosheets, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conductive polymers, enhancing the overall conductivity of the system. The nanoengineered surface chemistry allows for compatible direct assembly of bioreceptor molecules. CoVSense offers an inexpensive (<$2 kit) and fast/digital response (<10 min), measured using a customized hand-held reader (<$25), enabling data-driven outbreak management. The sensor shows 95% clinical sensitivity and 100% specificity (Ct<25), and overall sensitivity of 91% for combined symptomatic/asymptomatic cohort with wildtype SARS-CoV-2 or B.1.1.7 variant (N = 105, nasal/throat samples). The sensor correlates the N-protein levels to viral load, detecting high Ct values of ≈35, with no sample preparation steps, while outperforming the commercial rapid antigen tests. The current translational technology fills the gap in the workflow of rapid, point-of-care, and accurate diagnosis of COVID-19.

A compact, low-cost, and binary sensing (BiSense) platform for noise-free and self-validated impedimetric detection of COVID-19 infected patients.

Electrochemical immuno-biosensors are one of the most promising approaches for accurate, rapid, and quantitative detection of protein biomarkers. The two-working electrode strip is employed for creating a self-supporting system, as a tool for self-validating the acquired results for added reliability. However, the realization of multiplex electrochemical point-of-care testing (ME-POCT) requires advancement in portable, rapid reading, easy-to-use, and low-cost multichannel potentiostat readers. The combined multiplex biosensor strips and multichannel readers allow for suppressing the possible complex matrix effect or ultra-sensitive detection of different protein biomarkers. Herein, a handheld binary-sensing (BiSense) bi-potentiostat was developed to perform electrochemical impedance spectroscopy (EIS)-based signal acquisition from a custom-designed dual-working-electrode immuno-biosensor. BiSense employs a commercially available microcontroller and out-of-shelf components, offering the cheapest yet accurate and reliable time-domain impedance analyzer. A specific electrical board design was developed and customized for impedance signal analysis of SARS-CoV-2 nucleocapsid (N)-protein biosensor in spiked samples and alpha variant clinical nasopharyngeal (NP) swab samples. BiSense showed limit-of-detection (LoD) down to 56 fg/mL for working electrode 1 (WE1) and 68 fg/mL for WE2 and reported with a dynamic detection range of 1 pg/mL to 10 ng/mL for detection of N-protein in spiked samples. The dual biosensing of N-protein in this work was used as a self-validation of the biosensor. The low-cost (∼USD$40) BiSense bi-potentiostat combined with the immuno-biosensors successfully detected COVID-19 infected patients in less than 10 min, with the BiSense reading period shorter than 1.5 min, demonstrating its potential for the realization of ME-POCTs for rapid and hand-held diagnosis of infections.

A High Dynamic Range Dual 8×16 Capacitive Sensor Array for Life Science Applications.

This paper presents a fully integrated complementary metal-oxide-semiconductor (CMOS) capacitive sensor array for life science applications. This sensing device consists of an array of 16 × 16 interdigitated electrodes (IDEs) integrated with a charge-based readout and multiplexing circuitries on the same chip. This chip was implemented in 0.35 µm AMS CMOS process. This sensing device has a wide input capacitance range (ICR) of about 100 fF and a resolution of 150 aF, and the capability of temporal, spatial, and dielectric sensing. It makes it possible to develop a low-cost, multimodal, calibration-free sensing platform for life science applications. Here, we demonstrate and discuss the functionality and applicability of the proposed sensing device by introducing various chemical solvents including ethanol, methanol, and pure water. The simulation and experimental results achieved in this work have taken us one step closer to a fully automated calibration-free multimodal capacitive sensing platform for high-throughput drug development and other purposes.

Wide Input Dynamic Range Fully Integrated Capacitive Sensor for Life Science Applications.

This paper presents a new fully integrated CMOS capacitance sensor chip with a wider input dynamic range (IDR) compared to the state-of-the-art, suitable for a variety of life science applications. With the novel differential capacitance to current conversion topology, it achieves an IDR of about seven times higher compared to the previous charge based capacitive measurement (CBCM) circuits and about three times higher compared to the CBCM with cascode current mirrors. It also features a calibration circuitry consisting of an array of switched capacitors, interdigitated electrodes (IDEs) realized on the topmost metal layer, a current-controlled 300 MHz oscillator, and a counter-serializer to create digital output. The proposed sensor, fabricated in AMS 0.35 µm CMOS technology, enables a high-resolution measurement, equal to 416 aF, of physiochemical changes in the IDE with up to 1.27 pF input offset adjustment range (IOAR). With a measurement speed of 15 µs, this sensor is among the fast CMOS capacitive sensors in the literature. In this paper, we demonstrate its functionality and applicability and present the experimental results for monitoring 2 µL evaporating droplets of chemical solvents. By using samples of solvents with different conductivity and relative permittivity, a wide range of capacitance and resistance variations in the sample-IDE interface electric equivalent model can be created. In addition, the evaporating droplet test has inherently fast dynamic changes. Based on the results, our proposed device addresses the challenge of detecting small capacitance changes despite large parasitic elements caused by the ions in the solution or by remnants deposited on the electrode.