Stealth Surface Modification of Surface-Enhanced Raman Scattering Substrates for Sensitive and Accurate Detection in Protein Solutions

Reliable surface-enhanced Raman scattering (SERS) based biosensing in complex media is impeded by nonspecific protein adsorptions. Because Of the near-field effect of SERS, it is challenging to modify SERS-active substrates using conventional nonfouling materials without introducing interference from their SERS signals. Herein, we report a, stealth surface modification Strategy for sensitive, specific awl accurate detection of fructose in protein Solutions Using SERS by forming a mixed:self-assembled monolayer (SAM). The SAM,consists of a short zwitterionic thiol, N,N-dimethyl-cysteamine-carboxybetaine (CBT), and:a fructose probe 4-mercaptophenylboronic acid (4-MPBA). The specifically designed and synthesized CBT not only resists protein fouling effectively, but also has very weak Raman,activity-compared to 4-MPBA. Thus, the CBT SAM provides stealth surface modification to SERS-active substrates. The surface compositions of mixed SAMs were investigated using X-ray photoelectron spectroscopy (XPS) and SERS, and their nonfouling properties were Studied with a surface plasmon resonance (SPR) biosensor. The mixed SAM with a surface composition of 94% CBT demonstrated a very km bovine serum albumin (BSA) adsorption (similar to 3 ng/cm(2)), and moreover, only the 4-MPBA signal appeared in the SERS spectrum. With the use of this surface-modified SERS-active substrate, quantification of fructose over clinically relevant concentrations (0.01-1 mM) was achieved. Partial least-squares regression (PLS) analysis showed that the detection sensitivity and accuracy were maintained for the measurements in 1 mg/mL BSA solutions. This stealth surface modification strategy provides a novel route to introduce nonfouling property to SERS-active substrates for SERS biosensing in complex media.