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).

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.

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

Surface-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.

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.

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.

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.

Towards a fast, high specific and reliable discrimination of bacteria on strain level by means of SERS in a microfluidic device.

The interest in a fast, high specific and reliable detection method for bacteria identification is increasing. We will show that the application of vibrational spectroscopy is feasible for the validation of bacteria in microfluidic devices. For this purpose, reproducible and specific spectral pattern as well as the establishment of large databases are essential for statistical analysis. Therefore, short recording times are beneficial concerning the time aspect of fast identification. We will demonstrate that the requirements can be fulfilled by measuring ultrasonic busted bacteria by means of microfluidic lab-on-a-chip based SERS. With the applied sample preparation, high specificity and reproducibility of the spectra are achieved. Taking advantage of the SERS enhancement, the spectral recording time is reduced to 1 s and a database of 11,200 spectra is established for a model system E. coli including nine different strains. The validation of the bacteria on strain level is achieved accomplishing SVM accuracies of 92%. Within this contribution the potential of our approach of bacterial identification for future application is discussed, focusing on the time-benefit and the combination with other microfluidic applications.

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.