Enhancing the performance of paper-based electrochemical impedance spectroscopy nanobiosensors: An experimental approach

Xiao Li; Zhen Qin; Hao Fu; Ted Li; Ran Peng; Zhijie Li; James M Rini; Xinyu Liu

doi:10.1016/j.bios.2020.112672

Enhancing the performance of paper-based electrochemical impedance spectroscopy nanobiosensors: An experimental approach

Biosens Bioelectron. 2021 Apr 1:177:112672. doi: 10.1016/j.bios.2020.112672. Epub 2020 Oct 12.

Authors

Xiao Li¹, Zhen Qin², Hao Fu³, Ted Li³, Ran Peng², Zhijie Li⁴, James M Rini⁴, Xinyu Liu⁵

Affiliations

¹ Department of Mechanical Engineering, McGill University, Montreal, QC, Canada; Department of Chemistry, Stanford University, Stanford, CA, USA.
² Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada.
³ Department of Mechanical Engineering, McGill University, Montreal, QC, Canada.
⁴ Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
⁵ Department of Mechanical Engineering, McGill University, Montreal, QC, Canada; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada. Electronic address: xyliu@mie.utoronto.ca.

Abstract

Accurate, rapid, and low-cost molecular diagnostics is essential in managing outbreaks of infectious diseases, such as the pandemic of coronavirus disease 2019 (COVID-19). Accordingly, microfluidic paper-based analytical devices (μPADs) have emerged as promising diagnostic tools. Among the extensive efforts to improve the performance and usability of diagnostic tools, biosensing mechanisms based on electrochemical impedance spectroscopy (EIS) have shown great promise because of their label-free operation and high sensitivity. However, the method to improve EIS biosensing on μPADs is less explored. Here, we present an experimental approach to enhancing the performance of paper-based EIS biosensors featuring zinc oxide nanowires (ZnO NWs) directly grown on working electrodes (WEs). Through a comparison of different EIS settings and an examination of ZnO-NW effects on EIS measurements, we show that ZnO-NW-enhanced WEs function reliably with Faradaic processes utilizing iron-based electron mediators. We calibrate paper-based EIS biosensors with different morphologies of ZnO NWs and achieve a low limit of detection (0.4 pg ml^-1) in detecting p24 antigen as a marker for human immunodeficiency virus (HIV). Through microscopic imaging and electrochemical characterization, we reveal that the morphological and the electrochemical surface areas of ZnO-NW-enhanced WEs indicate the sensitivities and sensing ranges of the EIS nanobiosensors. Finally, we report that the EIS nanobiosensors are capable of differentiating the concentrations (blank, 10 ng ml^-1, 100 ng ml^-1, and 1 μg ml^-1) of IgG antibody (CR3022) to SARS-CoV-2 in human serum samples, demonstrating the efficacy of these devices for COVID-19 diagnosis. This work provides a methodology for the rational design of high-performance EIS μPADs and has the potential to facilitate diagnosis in pandemics.

Keywords: COVID-19; Electrochemical impedance biosensing; HIV; Microfluidic paper-based analytical devices; Nanowires; Point-of-care diagnosis.

Publication types

Evaluation Study

MeSH terms

Biosensing Techniques / instrumentation*
Biosensing Techniques / methods
COVID-19 / blood
COVID-19 / diagnosis*
COVID-19 Serological Testing / instrumentation*
COVID-19 Serological Testing / methods
Dielectric Spectroscopy / instrumentation*
Dielectric Spectroscopy / methods
Equipment Design
Humans
Lab-On-A-Chip Devices
Limit of Detection
Nanowires / chemistry
Paper
SARS-CoV-2 / isolation & purification*
Zinc Oxide / chemistry

Substances

Zinc Oxide