Micrometer-thick, porous, nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties

Development of coating technologies for electrochemical sensors that consistently exhibit antifouling activities when exposed to diverse and complex biological environments over extended time is vital for development more effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both exceptional antifouling and electroconducting properties that greatly enhance the sensitivity of electrochemical sensors. Nozzle-assisted printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores, which also contains electroconducting gold nanowires. Using this approach, the antifouling conductive coating can be deposited only on the surface of the working electrode, and not on the reference and counter electrodes, which greatly facilitates the fabrication and functionality of multiplexed electrochemical sensors. The layer effectively resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to previously described thinner (nanometer thick) antifouling electroconductive coating made with drop casting or a spin coating of the same thickness, the nozzle-printed sensors coated with this thick porous nanocomposite exhibited sensitivities that were enhanced by 3.75- to 17-fold when three different target biomolecules were tested. As a result, emulsion-coated, multiplexed electrochemical sensors coated were able to carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology may provide a way to address hurdles currently restricting the application of electrochemical sensors for point-of-care (POC) diagnostic applications, as well as their use in implantable devices and other healthcare monitoring systems. ### Competing Interest Statement J.C.L, P.J., S.P., and D.E.I. are listed as inventors on patents describing this technology. ### Funding Statement This work was supported by the funding from the Wyss Institute at Harvard University, Korea Institute of Energy Technology Evaluation and Planning (KETEP) grant funded by the Korea Government (MOTIE) (no. 20183010014470). This work also supported by the National Research Foundation of Korea (NRF-2021M3H4A1A03049049 and NRF-2022R1A2C2006076). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board (IRB) of Gyeongsang National University College of Medicine in Changwon, Korea gave ethical approval for this work (IRB approval number: 2022-10-012) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data needed to evaluate the conclusions of this work can be found in the paper and/or the Supplementary Materials.