Single-Component Electroactive Polymer Architectures for Non-Enzymatic Glucose Sensing.

Organic mixed ionic-electronic conductors (OMIECs) have emerged as promising materials for biological sensing, owing to their electrochemical activity, stability in an aqueous environment, and biocompatibility. Yet, OMIEC-based sensors rely predominantly on the use of composite matrices to enable stimuli-responsive functionality, which can exhibit issues with intercomponent interfacing. In this study, an approach is presented for non-enzymatic glucose detection by harnessing a newly synthesized functionalized monomer, EDOT-PBA. This monomer integrates electrically conducting and receptor moieties within a single organic component, obviating the need for complex composite preparation. By engineering the conditions for electrodeposition, two distinct polymer film architectures are developed: pristine PEDOT-PBA and molecularly imprinted PEDOT-PBA. Both architectures demonstrated proficient glucose binding and signal transduction capabilities. Notably, the molecularly imprinted polymer (MIP) architecture demonstrated faster stabilization upon glucose uptake while it also enabled a lower limit of detection, lower standard deviation, and a broader linear range in the sensor output signal compared to its non-imprinted counterpart. This material design not only provides a robust and efficient platform for glucose detection but also offers a blueprint for developing selective sensors for a diverse array of target molecules, by tuning the receptor units correspondingly

Interactions of Catalytic Enzymes with n-Type Polymers for High-Performance Metabolite Sensors

The tight regulation of the glucose concentration in the body is crucial for balanced physiological function. We developed an electrochemical transistor comprising an n-type conjugated polymer film in contact with a catalytic enzyme for sensitive and selective glucose detection in bodily fluids. Despite the promise of these sensors, the property of the polymer that led to such high performance has remained unknown, with charge transport being the only characteristic under focus. Here, we studied the impact of the polymer chemical structure on film surface properties and enzyme adsorption behavior using a combination of physiochemical characterization methods and correlated our findings with the resulting sensor performance. We developed five n-type polymers bearing the same backbone with side chains differing in polarity and charge. We found that the nature of the side chains modulated the film surface properties, dictating the extent of interactions between the enzyme and the polymer film. Quartz crystal microbalance with dissipation monitoring studies showed that hydrophobic surfaces retained more enzymes in a densely packed arrangement, while hydrophilic surfaces captured fewer enzymes in a flattened conformation. X-ray photoelectron spectroscopy analysis of the surfaces revealed strong interactions of the enzyme with the glycolated side chains of the polymers, which improved for linear side chains compared to those for branched ones. We probed the alterations in the enzyme structure upon adsorption using circular dichroism, which suggested protein denaturation on hydrophobic surfaces. Our study concludes that a negatively charged, smooth, and hydrophilic film surface provides the best environment for enzyme adsorption with desired mass and conformation, maximizing the sensor performance. This knowledge will guide synthetic work aiming to establish close interactions between proteins and electronic materials, which is crucial for developing high-performance enzymatic metabolite biosensors and biocatalytic charge-conversion devices

A nanobody-functionalized organic electrochemical transistor for the rapid detection of SARS-CoV-2 and MERS antigens at the physical limit

The COVID-19 pandemic highlights the need for rapid protein detection and quantification at the single-molecule level in a format that is simple and robust enough for widespread point-of-care applications. We here introduce a modular nanobody-organic electrochemical transistor architecture that enables the fast and specific detection and quantification of single-molecule to nanomolar protein antigen concentrations in complex bodily fluids. The sensor combines a new solution-processable organic semiconductor material in the transistor channel with the high-density and orientation-controlled bioconjugation of nanobody fusion proteins on disposable gate electrodes. It provides results after a 10 minutes exposure to 5 µL of unprocessed samples, maintains high specificity and single-molecule sensitivity in human saliva or serum, and is rapidly reprogrammed towards any protein target for which nanobodies exist. We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples