Label-free impedimetric immunosensor for point-of-care detection of COVID-19 antibodies

Abstract

The COVID-19 pandemic has posed enormous challenges for existing diagnostic tools to detect and monitor pathogens. Therefore, there is a need to develop point-of-care (POC) devices to perform fast, accurate, and accessible diagnostic methods to detect infections and monitor immune responses. Devices most amenable to miniaturization and suitable for POC applications are biosensors based on electrochemical detection. We have developed an impedimetric immunosensor based on an interdigitated microelectrode array (IMA) to detect and monitor SARS-CoV-2 antibodies in human serum. Conjugation chemistry was applied to functionalize and covalently immobilize the spike protein (S-protein) of SARS-CoV-2 on the surface of the IMA to serve as the recognition layer and specifically bind anti-spike antibodies. Antibodies bound to the S-proteins in the recognition layer result in an increase in capacitance and a consequent change in the impedance of the system. The impedimetric immunosensor is label-free and uses non-Faradaic impedance with low nonperturbing AC voltage for detection. The sensitivity of a capacitive immunosensor can be enhanced by simply tuning the ionic strength of the sample solution. The device exhibits an LOD of 0.4 BAU/ml, as determined from the standard curve using WHO IS for anti-SARS-CoV-2 immunoglobulins; this LOD is similar to the corresponding LODs reported for all validated and established commercial assays, which range from 0.41 to 4.81 BAU/ml. The proof-of-concept biosensor has been demonstrated to detect anti-spike antibodies in sera from patients infected with COVID-19 within 1 h.

Editors’ Choice—Challenges and Opportunities for Developing Electrochemical Biosensors with Commercialization Potential in the Point-of-Care Diagnostics Market

“…Integrating sample processing with biosensing.-The recent COVID-19 pandemic underscores the importance of rapid sampleto-result times combined with high sensitivity and specificity for ECS Sensors Plus, 2024 3 011601 infectious disease diagnostics. [216][217][218] As such, in addition to commercially available methods used for detecting viral nucleic acids (e.g., reverse transcription polymerase chain reaction), viral antibodies (e.g., enzyme-linked immunosorbent assay), and viral antigens (e.g., lateral flow immunoassay), numerous studies using aptamers, 166,167,[219][220][221][222] MIPs, [223][224][225] and antibodies 226,227 have also been reported for the diagnosis of COVID-19, with artificial intelligence holding promising potential for the prediction of disease severity. 228 Additional studies, reviewed in depth elsewhere, 95,[229][230][231][232] have pushed the field of biosensing forward by testing new assays using a large number of clinical samples, aiming to tackle issues related to sample-to-sample variability and nonspecific binding.…”

Recent Developments in the Design and Fabrication of Electrochemical Biosensors Using Functional Materials and Molecules

“…Thus, enormous efforts have been dedicated towards the design and development of novel electrochemical biosensors, due to which significant advances have recently taken place in the field of electrochemical biosensing, aptasensing, and immunosensing. Furthermore, electrochemical-based technologies such as wearables, continuous monitoring devices, implants, chips, and microfluidic devices are being developed [ 169 , 170 , 171 , 172 , 173 , 174 ]. Thus, we sought to write a summarized review of the recent advancements in the design and fabrication of electrochemical biosensor platforms using various tailor-made functional materials, molecules, and their sensible hybrids.…”

Bionanotechnology and bioMEMS (BNM): state-of-the-art applications, opportunities, and challenges

“…The underlying principle of nano-enabled detection of emerging infectious diseases is to fabricate an appropriate nano-system to immobilize and detect target bio-active molecules with characteristic functional structures. Various nanobiosensors have been devised based on dual responsive photoplasmonic, [68][69][70][71][72] field-effect-transistor (FET) and electrochemical technologies 73 and guided gene recognition 74 that have enabled clinical-grade testing of COVID-19. Further integration with machine learning and the internet-of-things (IoT) can aid in real-time diagnosis and decision-making.…”