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A fundamental question crucial to surface-enhanced spatially offset Raman spectroscopy (SESORS) imaging and implementing it in a clinical setting for in vivo diagnostic purposes is whether a SESORS image can be used to determine the exact location of an object within tissue? To address this question, multiple experimental factors pertaining to the optical setup in imaging experiments using an in-house-built point-collection-based spatially offset Raman spectroscopy (SORS) system were investigated to determine those critical to the three-dimensional (3D) positioning capability of SESORS. Here, we report the effects of the spatial offset magnitude and geometry on locating nanoparticles (NPs) mixed with silica powder as an imaging target through tissue and outline experimental techniques to allow for the correct interpretation of SESORS images to ascertain the correct location of NPs in the two-dimensional x, y-imaging plane at depth. More specifically, the effect of "linear offset-induced image drag" is presented, which refers to a spatial distortion in SESORS images caused by the magnitude and direction of the linear offset and highlight the need for an annular SORS collection geometry during imaging to neutralize these asymmetric effects. Additionally, building on these principles, the concept of "ratiometric SESORS imaging" is introduced for the location of buried inclusions in three dimensions. Together these principles are vital in developing a methodology for the location of surface-enhanced Raman scattering-active inclusions in three dimensions. This approach utilizes the relationship between the magnitude of the spatial offset, the probed depth, and ratiometric analysis of the NP and tissue Raman intensities to ultimately image and spatially discriminate between two distinct NP flavors buried at different depths within a 3D model for the first time. This research demonstrates how to accurately identify multiple objects at depth in tissue and their location using SESORS which addresses a key capability in moving SESORS closer to use in biomedical applications.

Quantitative drug imaging in live cells is a major challenge in drug discovery and development. Many drug screening techniques are performed in solution, and therefore do not consider the impact of the complex cellular environment in their result. As such, important features of drug-cell interactions may be overlooked. In this study, Raman microscopy is used as a powerful technique for semi-quantitative imaging of Strathclyde-minor groove binders (S-MGBs) in mammalian cells under biocompatible imaging conditions. Raman imaging determined the influence of the tail group of two novel minor groove binders (S-MGB-528 and S-MGB-529) in mammalian cell models. These novel S-MGBs contained alkyne moieties which enabled analysis in the cell-silent region of the Raman spectrum. The intracellular uptake concentration, distribution and mechanism were evaluated as a function of the p

Raman spectroscopy is a non-invasive technique that allows specific chemical information to be obtained from various types of sample. The detailed molecular information that is present in Raman spectra permits monitoring of biochemical changes that occur in diseases, such as cancer, and can be used for the early detection and diagnosis of the disease, for monitoring treatment, and to distinguish between cancerous and non-cancerous biological samples. Several techniques have been developed to enhance the capabilities of Raman spectroscopy by improving detection sensitivity, reducing imaging times and increasing the potential applicability for in vivo analysis. The different Raman techniques each have their own advantages that can accommodate the alternative detection formats, allowing the techniques to be applied in several ways for the detection and diagnosis of cancer. This feature article discusses the various forms of Raman spectroscopy, how they have been applied for cancer detection, and the adaptation of the techniques towards their use for in vivo cancer detection and in clinical diagnostics. Despite the advances in Raman spectroscopy, the clinical application of the technique is still limited and certain challenges must be overcome to enable clinical translation. We provide an outlook on the future of the techniques in this area and what we believe is required to allow the potential of Raman spectroscopy to be achieved for clinical cancer diagnostics., This article discusses the use of various Raman spectroscopy techniques and how they have been applied to different methods of detection for the diagnosis of cancer and in monitoring cancer treatment, with an outlook on how they can progress into a clinical environment.

Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint sig-nals of molecules and for the investigation of a series of surface chemical reactions. Many studies introduced quantita-tive applications of SERS in various fields and several SERS methods have been implemented for each specific applica- tion, ranging in performance characteristics, analytes used, instruments, and analytical matrices. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in high-ly- regulated environments is still considered risky and the perception of a poorly reproducible and insufficiently robust analytical technique has persistently retarded its routine implementation. Collaborative trials are a type of interlabora-tory study (ILS) frequently performed to ascertain the quality of a single analytical method. The idea of an ILS of quan- tification with SERS arose within the framework of Working Group 1 (WG1) of the COST Action BM1401 Ra-man4Clinics32 in an effort to overcome the problematic perception of quantitative SERS methods. Here we report the first interlaboratory SERS study ever conducted, involving 15 laboratories and 41 researchers. In this study we tried to define a methodology to assess the reproducibility and trueness of a quantitative SERS method, and to compare differ- ent methods. In our opinion, this is a first important step toward a “standardization” process of SERS protocols, not proposed by a single laboratory but by a larger community.

Minor structural changes in transition metal dichalcogenides can have dramatic effects on their electronic properties. This makes the quest for key parameters that can enable a selective choice between the competing metallic and semiconducting phases in the 2D MoTe2 system compelling. Herein, we report the optimal conditions at which the choice of the initial seed layer dictates the type of crystal structure of atomically-thin MoTe2 films grown by chemical vapour deposition (CVD). When Mo metal is used as a seed layer, phase-pure semiconducting 2H-MoTe2 is the only product. Conversely, MoO3 leads to the preferential growth of phase-pure metallic 1Tꞌ-MoTe2. The control over phase growth allows for simultaneous deposition of both 2H-MoTe2 and 1Tꞌ-MoTe2 phases on a single substrate during one CVD reaction. Furthermore, Rhodamine 6G dye can be detected using few-layered 1Tꞌ-MoTe2 films down to 5 nM concentration which is several orders of magnitude higher than the value observed for bulk 1Tꞌ-MoTe2.

Surface enhanced Raman Scattering (SERS) can be used as a novel way of probing local liquid composition and structure at solid-liquid interfaces. This is particularly important for understanding the mechanism of heterogeneous nucleation from solution, where solutes are present at relatively high concentrations. To obtain information about the solution composition and structure near a gold nanoparticle (AuNP) surface, which facilitates SERS, it is thus necessary to understand the role of the analyte in AuNP aggregation, and its effect on the SERS signal and the Raman signal from the bulk. We have used dynamic light scattering and UV-Vis spectroscopy to investigate how glycine influences the aggregation of citrate-functionalised gold nanoparticles (AuNPs), and thus the SERS response, in glycine aqueous solutions. At pH 4 the AuNP suspensions in aqueous solutions (without glycine) did not aggregate due to the electrostatic stabilisation by negatively charged citrate functional groups. However, the addition of glycine promoted aggregation of the AuNPs, concomitantly increasing the strength of the SERS signal. Under these conditions glycine is zwitterionic, and its effect on the colloidal stability of AuNPs is most likely due to its association with citrate, affecting its charge state, resulting in reduction of the electrostatic stabilisation of the AuNPs. Using SERS as a solid-liquid interface probe provides a window into an interplay of interfacial and colloidal phenomena in the AuNP suspensions.

We report that gold-coated nanodisk arrays of nearly micron periodicity have high figure of merit (FOM) and sensitivity necessary for plasmonic refractometric sensing, with the added benefit of suitability for surface-enhanced Raman scattering (SERS), large scale microfabrication using standard photolithographic techniques and a simple instrumental setup. Gold nanodisk arrays were covered with a gold layer to excite the Bragg modes (BM) which are the propagative surface plasmons localized by the diffraction from the disk array. This generated surface-guided modes, localized as standing waves, leading to highly confined fields confirmed by a mapping of the SERS intensity and numerical simulations with 3D finite element method (3D FEM). The optimal gold-coated nanodisk arrays were applied for refractometric sensing in transmission spectroscopy with better performance than nanohole arrays and they were integrated to a 96-well plate reader for detection of IgY proteins in the nM range in PBS. The potential for sensing in biofluids was assessed with IgG detection in 1:1 diluted urine. The structure exhibits a high FOM of up to 46, exceeding the FOM of structures supporting surface plasmon polaritons (SPPs) and comparable to more complex nanostructures, demonstrating that sub-wavelength features are not necessary for high performance plasmonic sensing.

Surface-enhanced Raman scattering (SERS) is of interest for biomedical analysis and imaging because of its sensitivity, specificity and multiplexing capabilities. The successful application of SERS for in vivo biosensing requires probes to be biocompatible and procedures to be minimally invasive, challenges that have respectively been met by developing new 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 must be addressed before SERS sees clinical use. Surface-enhanced Raman scattering (SERS) is a physical phenomenon first discovered in 1974. SERS has since been exploited for bioanalysis because of its high sensitivity and multiplexing capabilities. This Review describes the progress made and problems faced with respect to using in vivo SERS in humans.

Artificial enzymes have become an increasingly interesting area of research due to their many advantages over natural protein enzymes which are expensive, difficult to isolate and unable to stand harsh environments. An important area of this research involves using metal nanoparticles as artificial enzymes, known as nanozymes, which exhibit peroxidase-like activity enabling them to catalyse the oxidation of substrates such as 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2), giving a colorimetric response. Here we exploit the catalytic activity of silver nanoparticles (Ag NPs) in a surface based silver-linked immunosorbent assay (SLISA) to detect human C-reactive protein (CRP), an inflammatory marker. Ag NPs were conjugated to antibodies with specific recognition for the corresponding target antigenic molecule, CRP, and the Ag NPs were used to catalyse the oxidation of TMB by H2O2. The resulting coloured oxidation product was detected using SERRS. We demonstrate that Ag NPs can replace the enzymes used in a conventional ELISA and a detection limit of 1.09 ng mL−1 of CRP can be achieved. It indicates the promise for SLISAs for biomarker detection and opens the way for further assays of this nature to be created. This novel assay has the potential to be optimised to detect lower levels of CRP and can be further extended for the sensitive and specific detection of other relevant biomarkers.

We report a novel approach for patterning thermoresponsive hydrogels based on N,N-diethylacrylamide (DEAAm) and bifunctional Jeffamine ED-600 by dip-pen nanolithography (DPN). The direct writing of micron-sized thermoresponsive polymer spots was achieved with efficient control over feature size. A Jeffamine-based ink prepared through the combination of organic polymers, such as DEAAm, in an inorganic silica network was used to print thermosensitive arrays on a thiol-silanised silicon oxide substrate. The use of a Jeffamine hydrogel, acting as a carrier matrix, allowed a reduction in the evaporation of ink molecules with high volatility, such as DEAAm, and facilitated the transfer of ink from tip to substrate. The thermoresponsive behaviour of polymer arrays which swell/de-swell in aqueous solution in response to a change in temperature was successfully characterised by atomic force microscopy (AFM) and Raman spectroscopy: a thermally-induced change in height and hydration state was observed, respectively. Finally, we demonstrate that cells can adhere to and interact with these dynamic features and exhibit a change in behaviour when cultured on the substrates above and below the transition temperature of the Jeffamine/DEAAm thermoresponsive hydrogels. This demonstrates the potential of these micropatterned hydrogels to act as a controllable surface for cell growth.

Correction for ‘A novel nanozyme assay utilising the catalytic activity of silver nanoparticles and SERRS’ by Sian Sloan-Dennison et al., Analyst, 2017, 142, 2484–2490.

Correction for ‘Multiplex in vitro detection using SERS’ by Stacey Laing et al., Chem. Soc. Rev., 2016, 45, 1901–1918.

Tumor necrosis factor a is an inflammatory cytokine which has been linked with many infectious and inflammatory diseases. Detection and quantification of this key biomarker is commonly achieved by use of an enzyme-linked immunosorbent assay (ELISA). This fundamental technique uses the spectroscopic detection of a chromogen such as 3,3',5,5'-tetramethylbenzidine (TMB). Horseradish peroxidase (HRP), bound to the detection antibody, catalyzes the oxidation of TMB by hydrogen peroxide to generate colored products which may be measured spectrophotometrically. In this study we have used a conventional ELISA kit and shown that, by replacing the traditional colorimetric detection with resonance Raman spectroscopy, we can achieve 50 times lower detection limits and the potential for multiplexed analysis is increased. In this approach, the laser wavelength was tuned to be in resonance with an electronic transition of the oxidized TMB. The relative intensity of the enhanced Raman bands is proportional to the amount of TMB, thus providing a means of improved quantification. Furthermore, TMB is one of the most widely used chromogenic substrates for HRP-based detection and commercial ELISA test kits, indicating that this detection technique is applicable to a large number of target analytes.