Detection of COVID-19-related biomarkers by electrochemical biosensors and potential for diagnosis, prognosis, and prediction of the course of the disease in the context of personalized medicine.

As a more efficient and effective way to address disease diagnosis and intervention, cutting-edge technologies, devices, therapeutic approaches, and practices have emerged within the personalized medicine concept depending on the particular patient's biology and the molecular basis of the disease. Personalized medicine is expected to play a pivotal role in assessing disease risk or predicting response to treatment, understanding a person's health status, and, therefore, health care decision-making. This work discusses electrochemical biosensors for monitoring multiparametric biomarkers at different molecular levels and their potential to elucidate the health status of an individual in a personalized manner. In particular, and as an illustration, we discuss several aspects of the infection produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a current health care concern worldwide. This includes SARS-CoV-2 structure, mechanism of infection, biomarkers, and electrochemical biosensors most commonly explored for diagnostics, prognostics, and potentially assessing the risk of complications in patients in the context of personalized medicine. Finally, some concluding remarks and perspectives hint at the use of electrochemical biosensors in the frame of other cutting-edge converging/emerging technologies toward the inauguration of a new paradigm of personalized medicine.

Peptide-based simple detection of SARS-CoV-2 with electrochemical readout.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is considered one of the worst pandemic outbreaks worldwide. This ongoing pandemic urgently requires rapid, accurate, and specific testing devices to detect the virus. We report a simple electrochemical biosensor based on a highly specific synthetic peptide to detect SARS-CoV-2 Spike protein. Unlike other reported electrochemical biosensors involving nanomaterials or complex approaches, our electrochemical platform uses screen-printed gold electrodes functionalized with the thiolated peptide, whose interaction with the Spike protein is directly followed by Electrochemical Impedance Spectroscopy. The electrochemical platform was Spike protein concentration-dependent, with high sensitivity and reproducibility and a limit of detection of 18.2 ng/mL when tested in Spike protein commercial solutions and 0.01 copies/mL in lysed SARS-CoV-2 particles. The label-free biosensor successfully detected the Spike protein in samples from infected patients straightforwardly in only 15 min. The simplicity of the proposed format combined with an on-demand designed peptide opens the path for detecting other pathogen-related antigens.

SARS-CoV-2 electrochemical immunosensor based on the spike-ACE2 complex.

Rapid, straightforward, and massive diagnosis of coronavirus disease 2019 (COVID-19) is one of the more important measures to mitigate the current pandemics. This work reports on an immunosensor to rapidly detect the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunosensing device entraps the spike protein linked to angiotensin-converting enzyme host receptor (ACE2) protein in a sandwich between carboxylated magnetic beads functionalized with an anti-spike antibody and an anti-ACE2 antibody, further labeled with streptavidin (poly)horseradish peroxidase (HRP) reporter enzyme. The particles were confined at the surface of screen-printed gold electrodes, whose signal resulting from the interaction of the enzyme with a mediator was recorded in a portable potentiostat. The immunosensor showed a sensitivity of 0.83 µA∗mL/µg and a limit of detection of 22.5 ng/mL of spike protein, with high reproducibility. As a proof-of-concept, it detected commercial spike protein-supplemented buffer solutions, pseudovirions, isolated viral particles and ten nasopharyngeal swab samples from infected patients compared to samples from three healthy individuals paving the way to detect the virus closer to the patient.

Electrochemical genosensor for the specific detection of SARS-CoV-2.

Infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for the Coronavirus disease (COVID-19) and the current pandemic. Its mortality rate increases, demonstrating the imperative need for acute and rapid diagnostic tools as an alternative to current serological tests and molecular techniques. Features of electrochemical genosensor devices make them amenable for fast and accurate testing closer to the patient. This work reports on a specific electrochemical genosensor for SARS-CoV-2 detection and discrimination against homologous respiratory viruses. The electrochemical biosensor was assembled by immobilizing thiolated capture probes on top of maleimide-coated magnetic particles, followed by specific target hybridization between the capture and biotinylated signaling probes in a sandwich-type manner. The probes were rigorously designed bioinformatically and tested in vitro. Enzymatic complexes based on streptavidin-horseradish peroxidase linked the biotinylated signaling probe to render the biosensor electrochemical response. The genosensor showed to reach a sensitivity of 174.4 µA fM-1 and a limit of detection of 807 fM when using streptavidin poly-HRP20 enzymatic complex, detected SARS-CoV-2 specifically and discriminated it against homologous viruses in spiked samples and samples from SARS-CoV-2 cell cultures, a step forward to detect SARS-CoV-2 closer to the patient as a promising way for diagnosis and surveillance of COVID-19.