Recent progress in SERS biosensing

Abstract

This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.

Fig. 1

Scanning electron micrograph of a AgFON, a widely used substrate for SERS. Figure adapted from Ref. , reproduced with permission from the American Chemical Society.

Fig. 2

(A) SERS spectra of (a) a hybrid bilayer formed with DMPC, (b) a hybrid bilayer formed with DMPC incubated for 2 hours with deuterated-DMPC vesicles, and (c) a hybrid bilayer formed with deuterated-DMPC. The decrease in I_CH/ I_CS (2850 and 710 cm⁻¹, respectively) for the three different systems, as shown in the inset, clearly demonstrates exchange/transfer of lipids. (B) Kinetics of the transfer of deuterated lipids from vesicles to hybrid bilayers as obtained by monitoring the change in I_CH/ I_CS. The line is a first order exponential fit to the data points. Accompanied is a schematic of the plausible changes in hybrid bilayer composition. Figure adapted from Ref. , reproduced by permission of The Royal Society of Chemistry.

Fig. 3

A flatbed scanner image of Raman probes (A) before and (B) after Ag enhancement. (C) A SERS spectrum of one of the Ag spots. (D) Raman intensity of the 1192 cm⁻¹ as the laser is scanned across the chip from left to right. Figure adapted from Ref. , reproduced with permission from the American Academy for the Advancement of Science.

Fig. 4

Detection scheme for label-free protein sensing with SERS. The presence of protein induces the aggregation of Ag nanoparticles, which is then used to produce a strong SERS signal. Figure adapted from Ref. , reproduced by permission of the American Chemical Society.

Fig. 5

Schematic of SERS immunoassay. Multiple formats are available for detection: (A) shows a Au NP core coated with a shell into which extrinsic Raman labels and antibodies are immobilized, (B) shows a Au-coated Ag NP probe conjugated to both extrinsic Raman labels and capture antibodies, and (C) shows antibodies conjugated to a Au NP using extrinsic Raman labels. Figure adapted from Ref. , reproduced by permission of The Royal Society of Chemistry.

Fig. 6

In vivo cancer marker detection using surface enhanced Raman with scFv-antibody conjugated gold nanoparticles that recognize the tumor marker. (a) SERS spectra obtained from the tumor (red) and liver (blue) by using targeted nanoparticles and (b) non-targeted nanoparticles. (c) Photographs showing a laser beam focusing on tumor or liver sites. In vivo SERS spectra were obtained with a 785 nm laser at 20 mW and 2 sec integration. Figure adapted from Ref. , reproduced by permission of The Nature Publishing Group.

Scheme 1

A SERS probe consisting of a 13-nm-diameter Au nanoparticle functionalized with a Raman dye-labelled oligonucleotide. A three-component sandwich assay is used in a microarray format and the Raman probe detected, after Ag enhancing, by SERS. Figure adapted from Ref. , reproduced with permission from the American Academy for the Advancement of Science.