Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis

Abstract

In this paper, we review the state-of-the-art in surface-enhanced Raman scattering (SERS) based optical detection techniques with an application focus on cancer diagnostics. As we describe herein, SERS has several analytical, biological and engineering advantages over other methods including extremely high sensitivity, inherent molecular specificity of unlabeled targets, and narrow spectral bands. We review advances in both in vitro and in vivo applications of SERS and examine how technical issues with the technology are being addressed. A special technology focus is given to emerging optofluidic devices which aim to merge microfluidic and optical detection technologies into simple packages. We conclude with a brief discussion of some of the emerging challenges in the field and some of the approaches that are likely to enhance their application.

Vibrational spectroscopy for probing molecular-level interactions in organic films mimicking biointerfaces

“…It may be applied in-situ and in-vitro for biological samples, and works under a wide range of temperature and pressure conditions [180]. For biosensing and diagnosis, the major advantage of SERS over electrical or electrochemical biosensors is in the absence of interference from background conductivities and non-specific binding [180].…”

“…It may be applied in-situ and in-vitro for biological samples, and works under a wide range of temperature and pressure conditions [180]. For biosensing and diagnosis, the major advantage of SERS over electrical or electrochemical biosensors is in the absence of interference from background conductivities and non-specific binding [180]. In relation to other optical techniques such as surface plasmon resonance (SPR), SERS can be used as a specific measurement while SPR is based on the measure of mass accumulation, in which changes due to molecules non-specifically bound cannot be differentiated from the target.…”

“…In relation to other optical techniques such as surface plasmon resonance (SPR), SERS can be used as a specific measurement while SPR is based on the measure of mass accumulation, in which changes due to molecules non-specifically bound cannot be differentiated from the target. With respect to fluorescence techniques, besides the photostability (photobleaching of fluorescent probes), SERS presents simpler sample preparation [180]. Among SERS' important features are molecular identity (fingerprint spectrum), information about 3D structural changes (orientation, conformation) and intermolecular interactions.…”

Optofluidics for handling and analysis of single living cells

“…Raman spectroscopy has been used to determine cellular status, such as living cells [27], dead cells [28], apoptotic cells [29], proliferating cells [30], differentiating cells [31], tumor or healthy cells [26]. Raman spectroscopy can be integrated in microfluidic devices for having an accurate control over the biological sample (on single cells) [33,34] allowing to leave them over long period in physiological or conditioned environments, while at the same time obtaining biochemical information from the same sample (Figure 4a and 4b). The main advantages of such a technique are: -the capability to perform analysis in a label free manner, reducing the steps to pre-treat a biological sample; -the specificity of analysis due to a specific finger print for each biological substance; -the possibility to analyse biological substances in water solutions.…”

Integrated waveguide and nanostructured sensor platform for surface-enhanced Raman spectroscopy

“…These vibrational transitions are dependent on the molecules; therefore, the inelastic scattering can be used to identify functional subgroups of the test molecule. 1 Devices capable of molecular detection are of great interest for many applications including cancer cell detection, [2][3][4] drug analysis, 5,6 and explosives detection. 7,8 Although extremely useful for bulk sample identification, conventional Raman spectroscopy has limited applications as the level of detection of the inelastic-scattered light is very low.…”