Shrink-Polymer Based Antifouling Sensor for Electrochemical Detection of Small Molecules in Complex Biofluids

There is a growing demand to develop electrochemical sensors for directly detecting disease-related small molecules in body fluids, which is meaningful for disease diagnosis. However, the contamination from the high-concentration proteins in real samples impedes the electron transfer of the electrochemical electrode and reduces the sensitivity, leading to false positive results sometimes. In this article, we proposed a simple method to prepare an electrochemical sensor with a strong antifouling capacity based on the shrink polymer structure and electrostatic repulsion modification. The shrink polymer technique was optimized to create nano-wrinkles to limit the diffusion of large proteins by physical structures. Negatively charged bovine serum albumin was modified on the wrinkles by polydiallyl dimethylammonium chloride (PDDA), repelling most of the proteins in body fluids by electrostatic repulsion. The combined features enable the proposed biosensor to maintain over 93% of its original signal after exposure to high-concentration albumin, serum, and rabbit whole blood over 15 days, demonstrating pleasant antifouling capacity. This antifouling sensor exhibits good repeatability, a wide detecting range (15–
$1105 \mu \text{M}$
), and a low limit of detection (
$1.09 \mu \text{M}$
,
$3 \sigma $
/S) for dopamine in a protein-coexisting environment, confirming its potential feasibility in electrochemical diagnosis of diseases in serum or blood directly. These results demonstrated a further step to developing simple and robust antifouling biosensors by shrink polymer technique.