StarPEG-heparin biosensors for rapid and portable diagnostics in complex biofluids

Impedance spectroscopy-based biosensors are typically functionalized following two-dimensional immobilization strategies, with bioreceptors attached through crosslinkers. These methodologies may lead to a decreased receptor activity due to wrong orientation, conformational changes or limited interaction kinetics with the liquid sample. Entrapment of bioreceptors in hydrogels can tackle these issues offering a favourable three-dimensional fluid-like environment, while protecting the electrodes from biofouling in the presence of complex biological fluids at the same time. The star-shaped polyethylene glycol hydrogel doped with heparin (starPEG-heparin) represents a promising candidate, with its excellent hemocompatibility, but its biosensing performance has never been investigated. Here, we show the first demonstration of starPEG-heparin as a biosensor, using antibodies against immunoglobulin G as a model bioreceptor, and we compare it to the performance of other gels with alternative advantages: alginate, which provides easy fabrication and electrode regeneration possibilities, and silicate-based sol-gel, whose porosity can be tuned in a wide range. The starPEG-heparin outperforms the other two, being capable of detecting ultralow antigen concentrations down to the femtomolar levels, implemented in simple photolithography electrodes. We envision its integration in nanomaterial-based sensors which will further improve the sensitivity, and its application in full blood analysis or in implantable devices for in vivo biosensing.