Soluble polymeric system reducing non-specific interactions in plasmonic biosensor-based detection of...

Non-specific interactions in detection systems are among the main factors limiting the performance of surface-sensitive biosensor technologies. Here, we report on a new macromolecular blocker based on low-fouling poly[N-2-(hydroxypropyl)methacrylamide] (HPMA) copolymer containing hydrophobic comonomer units, which can reduce non-specific interactions improving the limit of detection when used in conjunction with a sandwich assay employing functional gold nanoparticles (AuNPs). The poly(HPMA) blocker adopts a relatively compact or collapsed conformation in PBS buffer, potentially indicating significant intramolecular interactions in an extended random coil. In a model experiment, we use this approach with a surface plasmon resonance biosensor for the detection of carcinoembryonic antigen, a biomarker of colorectal cancer. We demonstrate that the poly(HPMA) blocker reduced the AuNP non-specific binding and provided a high reduction of the non-specific binding when compared to conventional additives such as bovine serum albumin (BSA) and Tween. A combination of poly(HPMA) blocker and BSA was found to be the most effective additive, providing a 2.9-fold decrease of AuNP non-specific sensor response and a 2.8-fold improvement of the limit of detection compared to BSA alone.