(170d) Surface Functionalization and Non-Fouling Modification for Sugar Detection in Complex Media By Using SERS

A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. 4-Mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-3D plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group. The symmetry breaking of the 4-MPBA molecule upon fructose binding leads to the change of area ratio between totally symmetric 8a ring mode and non-totally symmetric 8b ring mode, which enables the detection. Meanwhile, N,N-Dimethyl-cysteamine-carboxybetaine (CBT), a zwitterionic based short thiol, was designed and synthesized as the non-fouling modification to resist non-specific protein adsorptions in complex media.  The CBT and 4-MPBA were mixed to form self-assembled monolayer on SERS-active surface. Albeit the surface is mostly occupied by CBT, the SERS spectrum is dominated by the 4-MPBA probe due to the sharp difference between their intrinsic Raman activities. The detection signal is amplified by the probe molecule and the background noise from complex media is reduced by the non-fouling modification. Quantitative detections of fructose in PBS, undiluted artificial urine and solutions with proteins were achieved with clinically relevant concentrations.