Graphene oxide surface blocking agents can increase the DNA biosensor sensitivity.

Graphene oxide adsorbs single-strand fluorescent probe DNA, and the adsorbed probe can be desorbed by adding the complementary target DNA. Using this method, many biosensor studies have been carried out. We recently proposed a two-step mechanism for this sensing reaction: non-specific probe displacement followed by hybridization in the solution. Only about one out of six added target DNA is hybridized with the adsorbed probe to generate signal, leading to relatively low sensitivity. In this work, we aim to test whether surface blocking agents can minimize non-specific target adsorption and increase hybridization efficiency. Over ten blocking agents (polymers, surfactants, and DNA) were screened based on their effect on probe DNA adsorption and target DNA induced probe desorption. DNA oligonucleotides show significant and controllable enhancement in sensor sensitivity. The effect of DNA length and sequence was systematically investigated. Under optimized conditions, the sensor sensitivity was enhanced by nearly 10-fold. Using the same blocking method, sensitivity enhancement of other targets was also achieved, including adenosine and Hg(2+) with DNA aptamer probes. This reported surface blocking strategy can generally improve graphene oxide and potentially other surface adsorption based biosensors for metal ions, small molecules, and DNA.