Sensitive and Fast Detection of Fructose in Complex Media via Symmetry Breaking and Signal Amplification Using Surface-Enhanced Raman Spectroscopy

Abstract

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. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional 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. Most importantly, 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 nontotally symmetric 8b ring mode, which enables the detection. The detection curves were obtained in phosphate-buffered saline (PBS) and in undiluted artificial urine at clinically relevant concentrations, and the limit of detection of 0.05 mM was achieved.

Hierarchical zwitterionic modification of a SERS substrate enables real-time drug monitoring in blood plasma

“…These include monosaccharides such as glucose and fructose, whereas protons or metal cations lack Raman activity completely3637. To detect these analytes indirectly, probe molecules or Raman reporters have been developed.…”

“…1a. They were fabricated via electron beam lithography following the same procedure reported previously37. On a 4-inch wafer, 70 pieces of SERS substrates, each with 4 of 50 × 50 μm Q3D-PNAs, were made to ensure high reproducibility from pattern to pattern and substrate to substrate.…”

Functionalized plasmonic nanostructure arrays for direct and accurate mapping extracellular pH of living cells in complex media using SERS

“…Gold Q3D-PNAs (50 μm  50 μm) with a square grid of 400 nm diameter and 100 nm spacing were fabricated by electron beam lithography (EBL) following the same method reported previously (Sun et al, 2014(Sun et al, , 2015. Scanning electron microscope (SEM, FEI Sirion) and tapping mode atomic force microscope (AFM, DI MultiMode with Nanoscope Iva controller) were used to characterize the dimensions of the nanostructures.…”

“…S1 in the Supporting information (SI). Q3D-PNAs were designed using finite-difference time-domain (FDTD) electromagnetic simulations and fabricated via EBL, which have demonstrated excellent tunable plasmonic and optical properties as well as strong and reproducible SERS signals (Sun et al, 2014;Xu et al, 2011). Fig.…”

Silicon Nanowire Biosensor for Highly Sensitive and Multiplexed Detection of Oral Squamous Cell Carcinoma Biomarkers in Saliva

“…[11][12][13][14] Although these label-based methods have good sensitivity, they suffer from some drawbacks, including challenges concerning the labeling procedures, tedious and time-consuming experimental procedures, thereby hindering them from more extensive applications. 15 In an attempt to overcome the above disadvantages, several label-free sensor technologies have been employed to detect biomarkers, such as surface plasmon resonance (SPR), 16 a quartz crystal microbalance (QCM), 17 atomic force microscopy (AFM), 18 surface-enhanced raman spectroscopy (SERS), 19 and a fieldeffect transistor (FET). [20][21][22][23][24][25] Among them, the FET biosensors have recently attracted tremendous attention due to their remarkable advantages of high sensitivity.…”