Surface-enhanced Raman spectroscopy for in vivo biosensing

Abstract

| Surface enhanced Raman scattering (SERS) is of interest for biomedical analysis and imaging due to its sensitivity, specificity and multiplexing capabilities. The successful application of SERS for in vivo biosensing necessitates probes to be biocompatible and procedures to be minimally invasive, challenges that have respectively been met by the design of nanoprobes and instrumentation. This Review presents recent developments in these areas, describing case studies in which sensors have been implemented, as well as outlining shortcomings that have to be addressed before SERS sees clinical use.In 1928, C. V. Raman first reported the scattering phenomenon that now bears his name.1,2 Raman scattering has since become a powerful analytical technique, including for biomedical applications, 3 where label-free and objective tissue diagnostics 4-6 ex vivo and in vivo, as well as drug-cell interaction studies in vitro have been conducted. [7][8][9] The majority of incident photons experience elastic (Rayleigh) scattering, with only about 1 in 10 7 photons undergoing inelastic (Raman) scattering. 10 In 1974, Fleischmann and co-workers described a phenomenon that would later become known as surface enhanced Raman scattering (SERS) 11 . They observed a large enhancement in inelastic scattering from pyridine when the analyte was adsorbed onto a Ag electrode, an effect that had previously been mentioned by the team of A. J. McQuillan in 1973, 12 with Van Duyne later attributing the signal enhancement to the roughened metal surface via the physical phenomenon he coined SERS.13 Unlike conventional Raman spectroscopy, SERS analyses require samples to be labelled, a disadvantage offset by the large intensity enhancement that makes SERS an important analytical tool with high sensitivity and low detection limits.14,15 The exact mechanism of SERS is not fully understood but an electromagnetic enhancement factor plays the major role 16 , whereby free electrons in a metal nanoparticle (NP) encounter applied radiation whose electromagnetic field varies at a frequency matching the oscillation frequency of electrons in the NPs. Such plasmon resonance at the NP surface arises from an intense electric field, which intensifies Raman modes arising from molecules near or attached to the NP surface. The Raman signals can also be enhanced due to the formation of chargetransfer complexes between the roughened metal surface and molecules bound to it. We now leave our discussion of the SERS mechanism, but refer readers interested in these fundamental principles to some comprehensive articles on the subject. [17][18][19] Well-known selection rules allow for one to predict if a given vibrational mode is infrared-and/or Raman-active. Indeed, by considering the magnitude of the change in dipole moment or polarizability associated with a vibration, one can rationalize infrared or Raman data, respectively. Compared to Raman spectroscopy, SERS involves analyte molecules interacting with a roughened metal substrate, such that the symmetry ...

Metal‐Dielectric Nanocavity for Real‐Time Tracing Molecular Events with Temperature Feedback

“…In our work we use Raman spectroscopy both for tracing the molecular events and nanoscale thermometry in real time enabled by the hybrid nanocavity. In this section, we firstly discuss how the nanocavity proposed acts as a Raman thermometer with sufficient accuracy and short acquisition time.…”

“…In order to trace the molecular events via Raman spectroscopy, one should enhance the collected RS signal from the molecules by placing them inside the nanocavity. In our case, the nanocavity itself represents the c‐Si NP with ∼5 nm oxide shell placed on 60 nm Au film with zero gap (inset in Figure c and Supporting Information, Section 1).…”

“…In our case, the nanocavity itself represents the c‐Si NP with ∼5 nm oxide shell placed on 60 nm Au film with zero gap (inset in Figure c and Supporting Information, Section 1). Such a design can provide ∼80 times field enhancement corresponding to 7 order of magnitude enhancement of RS which, in turn, is necessary for working with a single molecule . In addition, the molecular events can be induced by heat with precise control due to the resonant properties of the hybrid nanocavity.…”

SERS detection of food contaminants by means of portable Raman instruments

“…From the graph, one can notice that the number of publications in which portable Raman instruments are used for SERS detection has been significantly growing in the last 5–10 years. To the best of our knowledge, although a large number of articles and reviews have been published, also in recent years, on food, drugs and medicine, explosives and warfare, environment, and art preservation, no paper has been specifically dedicated to the use of portable instruments for the detection of these analytes. Aim of this review is to fill this gap, focusing on the SERS detection of food contaminants.…”

SERS Nanotags and Their Applications in Biosensing and Bioimaging

“…1) include a metal colloid for Raman signal enhancement, Raman labels/reporter linked on the metal surface for identification, a protective layer or shell for NP stabilization, and a ligand (e.g. an antibody) for recognising the target [26,65]. We will discuss briefly the chemical component and structure of SERS nanotags in this review.…”