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
Author Information
  1. Razieh Salahandish: 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. Pezhman Jalali: BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
  3. Hamed Osouli Tabrizi: Biologically Inspired Sensors and Actuators (BioSA), Department of Electrical Engineering and Computer Science, Lassonde School of Engineering, York University, Toronto, M3J1P3, Canada.
  4. Jae Eun Hyun: Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
  5. Fatemeh Haghayegh: BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
  6. Mahmood Khalghollah: 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.
  7. Azam Zare: BioMEMS and Bioinspired Microfluidic Laboratory, Department of Biomedical Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
  8. Byron M Berenger: 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.
  9. Yan Dong Niu: Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada. Electronic address: dongyan.niu@ucalgary.ca.
  10. Ebrahim Ghafar-Zadeh: 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.
  11. Amir Sanati-Nezhad: 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

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MeSH Term

Biosensing Techniques
COVID-19
Electrochemical Techniques
Humans
Reproducibility of Results
SARS-CoV-2

Word Cloud

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