Multiplex in vitro detection using SERS

The ability to detect multiple disease-related targets from a single biological sample in a quick and reliable manner is of high importance in diagnosing and monitoring disease. The technique known as surface enhanced Raman scattering (SERS) has been developed for the simultaneous detection of multiple targets present in biological samples. Advances in the SERS method have allowed for the sensitive and specific detection of biologically relevant targets, such as DNA and proteins, which could be useful for the detection and control of disease. This review focuses on the strengths of SERS for the detection of target molecules from complex mixtures and the clinical relevance of recent work combining SERS with multiplexed detection of biological targets

Surface-enhanced Raman spectroscopy for in vivo biosensing

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

From Raman to SESORRS : moving deeper into cancer detection and treatment monitoring

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

Mobile Health Technology Knowledge and Practices Among Patients of Safety-Net Health Systems in Washington State and Washington, DC

Purpose: Mobile health technology (mHealth) can reduce health disparities, but research on the health behaviors of low-income patients is needed. This study evaluates mHealth knowledge and practices of low-resource safety-net patients. Methods: We administered a 47-item questionnaire to 164 low-income patients accessing services at community health centers in the state of Washington and Washington, DC. Predictor variables included demographic factors: age, race, ethnicity, income. Outcome variables were smartphone knowledge (smartphones as a wellness tool), medical app knowledge (availability of medical-based apps), smartphone practices (ever used smartphones for wellness), health apps practices (ever used health-based apps), and medical apps practices (ever used medical-based apps). Multivariate logistic regression assessed relationships between predictor and outcome variables. Results: Mean age was 35.2 years (median: 34), and study cohort (N = 159) consisted of mostly women (68%), white race (36%), and income of < $20,000/year (63$20,000/year less likely than higher earners (OR: 3.13, 95% CI: 1.02–9.57); and 58% used medical apps, with Hispanics/Latinos significantly more likely than non-Hispanics/Latinos (OR: 6.38, 95% CI: 1.04–39.02). Conclusions: Safety-net patients use mobile devices for health promotion. Age and income are important predictive factors, suggesting a more tailored design of the technology is required for broad engagement and health equity

A novel nanozyme assay utilising the catalytic activity of silver nanoparticles and SERRS

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 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 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

Thermoresponsive polymer micropatterns fabricated by dip-pen nanolithography for a highly controllable substrate with potential cellular applications

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

Advancing SERS as a quantitative technique : challenges, considerations, and correlative approaches to aid validation

Surface-enhanced Raman scattering (SERS) remains a significant area of research since it’s discovery 50 years ago. The surface-based technique has been used in a wide variety of fields, most prominently in chemical detection, cellular imaging and medical diagnostics, offering high sensitivity and specificity when probing and quantifying a chosen analyte or monitoring nanoparticle uptake and accumulation. However, despite its promise, SERS is mostly confined to academic laboratories and is not recognised as a gold standard analytical technique. This is due to the variations that are observed in SERS measurements, mainly caused by poorly characterised SERS substrates, lack of universal calibration methods and uncorrelated results. To convince the wider scientific community that SERS should be a routinely used analytical technique, the field is now focusing on methods that will increase the reproducibility of the SERS signals and how to validate the results with more well-established techniques. This review explores the difficulties experienced by SERS users, the methods adopted to reduce variation and suggestions of best practices and strategies that should be adopted if one is to achieve absolute quantification

Effect of glycine on aggregation of citrate-functionalised gold nanoparticles and SERS measurements

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

Exceptional AGN-driven turbulence inhibits star formation in the 3C 326N radio galaxy

We detect bright [CII]158μm line emission from the radio galaxy 3C 326N at z=0.09, which shows weak star formation (SFR⊙~yr−1) despite having strong H2 line emission and 2×109M⊙ of molecular gas. The [CII] line is twice as strong as the 0-0S(1) 17μm H2 line, and both lines are much in excess what is expected from UV heating. We combine infrared Spitzer and Herschel data with gas and dust modeling to infer the gas physical conditions. The [CII] line traces 30 to 50% of the molecular gas mass, which is warm (70−3. The [CII] line is broad with a blue-shifted wing, and likely to be shaped by a combination of rotation, outflowing gas, and turbulence. It matches the near-infrared H2 and the Na D optical absorption lines. If the wing is interpreted as an outflow, the mass loss rate would be larger than 20M⊙/yr, and the depletion timescale shorter than the orbital timescale (108yr). These outflow rates may be over-estimated because the stochastic injection of turbulence on galactic scales can contribute to the skewness of the line profile and mimic outflowing gas. We argue that the dissipation of turbulence is the main heating process of this gas. Cosmic rays can also contribute to the heating but they require an average gas density larger than the observational constraints. We show that strong turbulent support maintains a high gas vertical scale height (0.3-4kpc) in the disk and can inhibit the formation of gravitationally-bound structures at all scales, offering a natural explanation for the weakness of star formation in 3C 326N. To conclude, the bright [CII] line indicates that strong AGN jet-driven turbulence may play a key role in enhancing the amount of molecular gas (positive feedback) but yet can prevent star formation on galactic scales (negative feedback)

Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy

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 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 pKa of the tail group, morpholine and amidine, for S-MGB-528 and S-MGB-529, respectively. Although S-MGB-529 had a higher binding affinity to the minor groove of DNA in solution phase measurements, the Raman imaging data indicated that S-MGB-528 showed a greater degree of intracellular accumulation. Furthermore, using high resolution stimulated Raman scattering (SRS) microscopy the initial localisation of S-MGB-528 was shown to be in the nucleus before accumulation in the lysosome, which was demonstrated using a multimodal imaging approach. This study highlights the potential of Raman spectroscopy for quantitative drug imaging studies and highlights the importance of imaging techniques to investigate drug-cell interactions, to better inform the drug design process