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

Razieh Salahandish; Pezhman Jalali; Hamed Osouli Tabrizi; Jae Eun Hyun; Fatemeh Haghayegh; Mahmood Khalghollah; Azam Zare; Byron M Berenger; Yan Dong Niu; Ebrahim Ghafar-Zadeh; Amir Sanati-Nezhad

doi:10.1016/j.bios.2022.114459

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

Biosens Bioelectron. 2022 Oct 1:213:114459. doi: 10.1016/j.bios.2022.114459. Epub 2022 Jun 14.

Affiliations

¹ BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
² BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
³ Biologically Inspired Sensors and Actuators (BioSA), Department of Electrical Engineering and Computer Science, Lassonde School of Engineering, York University, Toronto, M3J1P3, Canada.
⁴ Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
⁵ BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Department of Electrical and Software Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
⁶ Department of Pathology and Laboratory Medicine, University of Calgary, 3535 Research Rd. Calgary, Alberta, T2L 1Y1, Canada; Alberta Public Health Laboratory, Alberta Precision Laboratories, 3330 Hospital Drive, Calgary, Alberta, T2N 4W4, Canada.
⁷ Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada. Electronic address: dongyan.niu@ucalgary.ca.
⁸ Biologically Inspired Sensors and Actuators (BioSA), Department of Electrical Engineering and Computer Science, Lassonde School of Engineering, York University, Toronto, M3J1P3, Canada. Electronic address: egz@cse.yorku.ca.
⁹ BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Department of Mechanical and Manufacturing Engineering, University of Calgary, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta, T2N 1N4, Canada. Electronic address: amir.sanatinezhad@ucalgary.ca.

Abstract

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.

Keywords: Bi-potentiostat; Electrochemical biosensing; Point-of-care; Rapid tests; SARS-CoV-2.

MeSH terms

Biosensing Techniques* / methods
COVID-19* / diagnosis
Electrochemical Techniques
Humans
Reproducibility of Results
SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants