Oxidative coupling for facile, stable carbon modification with DNA and proteins

Modification of electrodes with biomolecules is an essential first step for the development of biosensors. Conventionally, gold electrodes are used because of their ease of modification with thiolated biomolecules. However, carbon screen-printed electrodes (SPEs) are gaining popularity for the development of cost-effective platforms, as they do not require precious metals for the work-ing electrode and are more consistent than most equivalent gold screen-printed electrodes. However, their universal modification with biomolecules remains a challenge; the majority of work to-date relies on non-specific amide bond formation to chemical handles on the electrode surface. By combining facile and consistent electrochemical modification to add an aniline handle to elec-trodes with a specific and biocompatible bioorthogonal oxidative coupling reaction, we can attach DNA and proteins to carbon electrodes. Importantly, for both proteins and DNA, the biomolecules maintain activity following coupling, ensuring that the DNA is in a biologically-relevant conformation and that proteins remain folded following coupling. We have further demonstrated the ability to generate self-assembled whole-cell films on these electrodes using DNA-directed immobilization to DNA-modified elec-trodes. This work provides an important platform for the modification of inexpensive carbon SPEs and is anticipated to be appli-cable to any carbon-based electrode material.