Anne März

Surface-enhanced Raman spectroscopy (SERS): progress and trends.

AbstractSurface-enhanced Raman spectroscopy (SERS) combines molecular fingerprint specificity with potential single-molecule sensitivity. Therefore, the SERS technique is an attractive tool for sensing molecules in trace amounts within the field of chemical and biochemical analytics. Since SERS is an ongoing topic, which can be illustrated by the increased annual number of publications within the last few years, this review reflects the progress and trends in SERS research in approximately the last three years. The main reason why the SERS technique has not been established as a routine analytic technique, despite its high specificity and sensitivity, is due to the low reproducibility of the SERS signal. Thus, this review is dominated by the discussion of the various concepts for generating powerful, reproducible, SERS-active surfaces. Furthermore, the limit of sensitivity in SERS is introduced in the context of single-molecule spectroscopy and the calculation of the ‘real’ enhancement factor. In order to shed more light onto the underlying molecular processes of SERS, the theoretical description of SERS spectra is also a growing research field and will be summarized here. In addition, the recording of SERS spectra is affected by a number of parameters, such as laser power, integration time, and analyte concentration. To benefit from synergies, SERS is combined with other methods, such as scanning probe microscopy and microfluidics, which illustrates the broad applications of this powerful technique. FigureVarious SERS substrates visualized using scanning electron microscopy

Towards a quantitative SERS approach--online monitoring of analytes in a microfluidic system with isotope-edited internal standards.

In this contribution a new approach for quantitative measurements using surface-enhanced Raman spectroscopy (SERS) is presented. Combining the application of isotope-edited internal standard with the advantages of the liquid-liquid segmented-flow-based approach for flow-through SERS detection seems to be a promising means for quantitative SERS analysis. For the investigations discussed here a newly designed flow cell, tested for ideal mixing efficiency on the basis of grayscale-value measurements, is implemented. Measurements with the heteroaromatics nicotine and pyridine using their respective deuterated isotopomers as internal standards show that the integration of an isotopically labeled internal standard in the used liquid-liquid two-phase segmented flow leads to reproducible and comparable SERS spectra independent from the used colloid. With the implementation of an internal standard into the microfluidic device the influence of the properties of the colloid on the SERS activity can be compensated. Thus, the problem of a poor batch-to-batch reproducibility of the needed nanoparticle solutions is solved. To the best of our knowledge these are the first measurements combining the above mentioned concepts in order to correct for differences in the enhancement behaviour of the respective colloid.

Bioanalytical application of surface- and tip-enhanced Raman spectroscopy

Due to its fingerprint specificity and trace‐level sensitivity, surface‐enhanced Raman spectroscopy (SERS) is an attractive tool in bioanalytics. This review reflects the research in this highly interesting topic of the last 3–4 years. The detection of the SERS signature of biomolecules up to microorganisms and cells is introduced. Labeling using modified nanoparticles (SERS tags) is also introduced. In order to establish biomedical applications, SERS analysis is performed in complex matrices such as body fluids. Furthermore, the SERS technique is combined with other methods such as microfluidic devices for online monitoring and scanning probe microscopy (i.e. tip‐enhanced Raman spectroscopy, TERS) to investigate nanoscaled features. The present review illustrates the broad application fields of SERS and TERS in bioanalytics and shows the great potential of these methods for biomedical diagnostics.

Droplet formation via flow-through microdevices in Raman and surface enhanced Raman spectroscopy—concepts and applications

This review outlines concepts and applications of droplet formation via flow-through microdevices in Raman and surface enhanced Raman spectroscopy (SERS) as well as the advantages of the approach. Even though the droplet-based flow-through technique is utilized in various fields, the review focuses on implementing droplet-based fluidic systems in Raman and SERS as these highly specific detection methods are of major interest in the field of analytics. With the combination of Raman or SERS with droplet-based fluidics, it is expected to achieve novel opportunities for analytics. Besides the approach of using droplet-based microfluidic devices as a detection platform, the unique properties of flow-through systems for the formation of droplets are capitalized to produce SERS active substrates and to accomplish uniform sample preparation. Within this contribution, previous reported applications on droplet-based flow-through Raman and SERS approaches and the additional benefit with regard to the importance in the field of analytics are considered.

Detection of thiopurine methyltransferase activity in lysed red blood cells by means of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS)

In this contribution, the great potential of surface enhanced Raman spectroscopy (SERS) in a lab-on-a-chip (LOC) device for the detection of analyte molecules in a complex environment is demonstrated. Using LOC-SERS, the enzyme activity of thiopurine S-methyltransferase (TPMT) is analysed and identified in lysed red blood cells. The conversion of 6-mercaptopurine to 6-methylmercaptopurine catalysed by TPMT is observed as it gives evidence for the enzyme activity. Being able to determine the TPMT activity before starting a treatment using 6-mercaptopurine, an optimized dosage can be applied to each patient and serious toxicity appearing within thiopurine treatment will be prevented.

Polyacrylamid/silver composite particles produced via microfluidic photopolymerization for single particle-based SERS microsensorics.

A micro-continuous-flow process was applied for the preparation of swellable polyacrylamide particles incorporating silver nanoparticles. These sensor particles are formed from a mixture of a colloidal solution of silver nanoparticles and monomer by a droplet-based procedure with in situ photoinitiation of polymerization and a subsequent silver enforcement in batch. The obtained polymer composite particles show a strong SERS effect. Characteristic Raman signals of aqueous solutions of adenine could be detected down to 0.1 μM by the use of single sensor particles. The chosen example demonstrates that the composite particles are suitable for quantitative microanalytical procedures with a high dynamic range (3 orders of magnitude for adenine).

Online-calibration for reliable and robust lab-on-a-chip surface enhanced Raman spectroscopy measurement in a liquid/liquid segmented flow.

Concerning the usability of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS) for analytical tasks applying chemometric data evalutation, a secure, reproducible, and stable data output independent of inconsistent ambient conditions has to be accomplished. In this contribution, we present a new approach to achieve reliable and robust measurements based on segmented flow LOC-SERS via online-wavenumber calibration.

Fluorescence dye as novel label molecule for quantitative SERS investigations of an antibiotic.

Within this contribution, the proof-of-principle for a new concept for indirect surface-enhanced Raman spectroscopy (SERS) detection is presented. The fluorescence dye FR-530 is applied as a label molecule for the antibiotic erythromycin. The antibiotic binds directly to the label molecule. Changes within the SERS spectrum of the fluorescence dye appearing with the presence of the antibiotic are utilized for the detection and quantitative investigations of erythromycin. With the new concept of binding the label molecule directly to the analyte molecule, the application of linkage compounds like antibodies or any other recognition molecules becomes dispensable.

The implementation of an isotope-edited internal standard for quantification of lowest drug concentrations using surface enhanced Raman spectroscopy (SERS) in a lab on a chip device

The application of surface enhanced Raman spectroscopy in combination with a microfluidic device and an isotopeedited internal standard seems to be a promising way for a new approach for quantitative SERS measurements. An innovative lab on a chip system offers the possibility for reproducible, quantitative online SERS measurements based on the application of isotope labelled internal standards and liquid/liquid segmented flow based flow-through Raman detection. Errors caused by the used method can be compensated by using an internal standard.

Online Segment Detection by Zero-Order Diffraction of Inelastic Scattered Light for Raman Spectroscopy in a Microfluidic Device

The application of microfluidic diagnostic systems is becoming more and more important for life sciences in general. Especially the development of ‘lab on a chip’ (LOC) systems with integrated optical detection units has been rising over the last few years, due to the applicability of such systems in point-of-care diagnostics in home care or field applications. Droplet-based microfluidic systems, where sample droplets are processed in microfluidic networks became a powerful platform for LOC technology. A promising approach concerning this field is for example microfluidic Raman spectroscopy. Raman spectroscopy is successfully carried out in a microfluidic device applying a liquid/liquid segmented flow, where analyte-containing droplets (ACD) are formed in a carrier fluid like e.g. oil. However the detection within this system is limited as information of both phases, ACD and carrier fluid, are collected and therefore the acquisition time for each spectrum is relatively small. An improvement can be achieved by employing a trigger system, which allows the measurement of only ACD and accordingly an increase of the integration time. The challenge of implementing a trigger is to maintain a setup, which is compact with regard to a point-of-care application and allows the detection of the inelastic scattered Raman light without additional attenuation. In this contribution a new approach for the implementation of a trigger in a prototype setup for microfluidic Raman measurements is introduced. The feasibility of ACD detection by measuring not just the first-order diffraction but also the zero-order diffraction of the inelastic scattered light will be demonstrated.