G.
Di Martino†
a,
H.
Fleming†
b,
M.
Kamp†
*c and
F.
Lussier†
d
aNanoPhotonics Centre, Cavendish Laboratory, University of Cambridge, CB3 0HE, UK
bEaStCHEM, School of Chemistry, University of Edinburgh, EH9 3FJ Edinburgh, UK
cMelville Laboratory for Polymer Synthesis, University of Cambridge, CB2 1EW, UK. E-mail: mk841@cam.ac.uk
dDepartment of Chemistry, Université de Montréal, H3C 3J7, Canada
First published on 16th November 2017
The 2017 Faraday Discussion on Surface Enhanced Raman Scattering (SERS) attracted more than a hundred delegates from a broad spectrum of backgrounds and experience levels, bringing together leading scientists involved in the long living field of SERS. The meeting gave an overview of the liveliness of the topic, characterised by open questions and fascinating science still to discover. In the following, we discuss the topics covered during this meeting and briefly highlight the content of each presentation.
The Faraday Discussions are unique international discussion meetings that focus on rapidly developing areas of chemistry and their interfaces with other scientific disciplines. The Discussions were founded in 1902; it was an idea conceived by Frederick S. Spiers who later became the Faraday Discussions Secretary of the Faraday Society. In line with the format of Faraday Discussions, all of the speakers submitted a paper prior to this meeting, which was made available for all of the participants to read before the event. During their respective sessions, the presenters were given 5 minutes each to briefly summarize the main findings of their work, followed by an open discussion with 30 minutes allotted for public and live peer review of each article contributed.
The discussions were preceded by a brief introduction from Prof. D. Graham on the topic of the meeting (Fig. 2a) and an introduction to the Faraday Discussions' format by the RSC Publishing Editors for the event, Sarah Sharp and Alexander Whiteside. The president of the Faraday Society Prof. E. Campbell (University of Edinburgh, UK) conferred the Spiers Memorial Award to Prof. R. Van Duyne (Northwestern University, USA) for his outstanding contribution to the SERS community (Fig. 2b).
Fig. 2 (a) Prof. D. Graham gives a short introduction to the meeting. (b) Prof. R. Van Duyne receives the Spiers Memorial Award from the president of the Faraday Society, Prof. E. Campbell. |
The meeting was divided into four sessions, which focused on particular aspects of SERS: (1) the theory of SERS enhancement, (2) ultrasensitive and towards single molecule SERS, (3) SERS in biology/biomedical SERS and (4) Analytical SERS. The opening lecture was given by Prof. R. Van Duyne, while the concluding remarks were given by Prof. M. Porter (University of Utah, USA).
Fig. 3 (a) The geometry of a plasmonic nanodimer on a SiO2/Si substrate. (b) Exemplary nanodimer between the electrodes used for the dielectrophoresis. (c) SEM images of 6T@CNT after deposition. The scale bars in (b) and (c) are 200 nm. Reproduced from DOI: 10.1039/C7FD00127D with permission from The Royal Society of Chemistry. |
According to Prof. J. Baumberg (University of Cambridge, UK), who chaired this session, “getting the quantum description correct is a major advance and the realisation that this mirrors the optomechanical descriptions which emerged in physics within the last 5 years provides important insights which will help develop the field of coherent Raman spectroscopies. Modelling of specific systems is also of much interest. Using carbon nanotubes as micro-vessels attached to plasmonics resonators, or semiconductor surfaces, or tip geometries under bias, all take better-understood theories and for us to try and apply them in new contexts.” From his point of view, “the CNT loading is just at a first step and more work will be very valuable. Experimental data for this and the other systems is crucial to provide verification of some of the predictions made and this is at an early stage. The theories will have to be modified in light of this. Finally, the introduction of further tuneable plasmonics at liquid surfaces is starting to become viable and is of much intrigue.” The very large number and range of questions in this session shows the liveliness of the interest and the emerging science that continues to develop.
Fig. 4 Theoretical calculations of the emission from a single dipole at a glass–air interface with φ = 0° and θ varying from 0° to 30°. Adapted from DOI: 10.1039/C7FD00163K with permission from the Royal Society of Chemistry. |
According to Prof. J. Edel (Imperial College London, UK), chair of the session, one of the biggest challenges is related to the selectivity of SERS at low concentrations, since single molecule detection usually implies the presence of spectral features, e.g. blinking (on/off signal), variation in the Raman band relative intensities and also variation in the frequency of specific Raman bands. Another important point discussed during the session was how efficiently we can screen for specific target analytes in complex mixtures with highly sensitive sensors. In addition to high selectivity, SERS also has a great capability for multiplexing on account of its intrinsic small bandwidth. However, although SERS has a high multiplexing potential compared to its most renowned competitor, fluorescence, few examples of true multiplexing SERS are currently present in the literature. Finally, an essential requirement for quantitative results is the use of reproducible and highly sensitive SERS substrates in order to ensure routinely quantitative measurements over a large dynamic range.
Fig. 5 Prof. R. Goodacre speaks in the third session: SERS in biology/biomedical SERS (Photo taken by Prof. D. Graham). Graph: PC-DFA scores plot of the pre-processed SERS spectral data of E. coli cells cultivated on different ratios of unlabelled (12C and 14N) and isotopically labelled 13C and/or 15N growth substrates. Adapted from DOI: 10.1039/C7FD00150A with permission from the Royal Society of Chemistry. |
After a short break, the session resumed with a method of detecting galectin in real-time using glycan-decorated gold nanoparticles, presented by J. Langer (CIC biomaGUNE, Spain). By altering the densities of the Raman reporters on the surface of the gold nanoparticles, the aggregation dynamics of the particles could be tuned (DOI: 10.1039/C7FD00123A). Prof. J.-F. Masson (University of Montreal, Canada) followed up by presenting an interesting semi-quantitative SERS approach for neurotransmitter sensing near neurons throughout multiple stimulated dopamine secretion cycles (DOI: 10.1039/C7FD00131B and Fig. 6). This novel technique, referred to as dynamic SERS optophysiology (D-SERS), allowed the multiplex sensing of five neurotransmitters under physiological conditions and constitutes a strong proof-of-concept for the potential application of SERS to study normal and pathological cellular functions. The ability to acquire SERS data without altering the biological sample in any way has been a difficult feat, and therefore reproducibility has been a problem for SERS on biological samples. Using immuno-Raman microspectroscopy (iSERS), the repeated imaging of a single cell was demonstrated by Prof. S. Schlücker (University of Duisburg-Essen, Germany; DOI: 10.1039/C7FD00135E). In the closing paper of the session, the focus was on the highly debated issue of “What do we actually see in intracellular SERS?” (DOI: 10.1039/C7FD00156H). Prof. S. Mahajan (University of Southampton, UK) explored the extent of how experimental conditions can affect gold nanoparticle internalisation, which in turn affect cell metabolism and induce changes. The discussion on the topic afforded the consensus that there is a need to move toward a standard methodology of nanoparticle treatments in order to validate intracellular SERS experiments.
Fig. 6 Scanning electron microscopy (SEM) image of the D-SERS nanosensor coated with nanoraspberries. Adapted from DOI: 10.1039/C7FD00131B with permission from The Royal Society of Chemistry. |
Prof. K. Faulds (University of Strathclyde, UK), chair of the session, remarked: “Biological and biomedical SERS has advanced greatly in the last 20 years and, in particular, since the first Faraday SERS meeting in 2005. The applications covered at the meeting ranged from bacterial and cell imaging to in vitro assays for enzyme activity, small molecule and protein detection. One of the greatest achievements in the field is that we are now able to routinely make sensitive, quantitative measurements and obtain rapid, high resolution images from single cells/bacteria that give us a huge amount of information about a system. One of the biggest challenges in biological SERS is standardisation of approaches. Differences between research groups in synthesising and functionalising nanoparticles result in slightly different surface chemistry, SERS response and toxicity. This affects the reproducibility of experiments between different laboratories and as a community we need to ensure that all conditions, the appropriate characterisation techniques utilized (particle size, zeta potential, extinction), and that the synthesis methods, buffers/media used, and measuring cellular uptake and toxicity, are all carefully reported. These issues, as well as the use of robust and reliable data analysis methods, were discussed during the meeting.”
The morning part of the session was opened by Prof. Z.-Q. Tian (Xiamen University, China) with a fascinating talk on expanding the use of SERS to non-traditional (weakly SERS-active) substrates and even to non-SERS-active substrates such as aluminium oxide (DOI: 10.1039/C7FD00144D, see Fig. 7). In the second talk, Prof. L. Hardwick (University of Liverpool, UK) showed how SHINERS can be exploited to study chemical processes at the surfaces of battery electrode materials, both on the lithium metal anode and carbon cathode of a LiO2 cell (DOI: 10.1039/C7FD00151G). Prof. P. Vikesland (Virginia Tech, USA) discussed how to use the Rayleigh band intensity as a parameter for the normalization of SERS intensity (DOI: 10.1039/C7FD00125H). Finally, Dr B. de Nijs (University of Cambridge, UK) demonstrated that SERS is able explore the local environment in a nano-gap as it is sensitive to the different configurational states of molecules and even allows for the detection of hydrogen bonding (DOI: 10.1039/C7FD00147A). In his talk, Prof. Z.-Q. Tian remarked on the importance of translating SERS to markets: “The field of SERS has a very low entry level because nanoparticles can now be produced easily following published literature. This reflects in a large body of work and citations on SERS. However, the actual number of user products based on SERS is quite low. We can infer that translating SERS to markets is not easy.” A frequently suggested reason for this discrepancy is the problem with reproducibility between SERS studies, but Prof. R. Goodacre reminded the delegates that “SERS is often ‘undersold’ as not reproducible. However, in general it is very reproducible. The issue is that different applications require different platforms and substrates.” In several presentations, experimental and computational techniques were mentioned which can indeed handle such sources of variability, among which are principle component analysis (Prof. R. Goodacre, Dr B. de Nijs), the Rayleigh band intensity (Prof. P. Vikesland) and internal standards (Prof. R. Van Duyne).
Fig. 7 Different strategies to probe SERS-active materials and inactive materials. Adapted from DOI: 10.1039/C7FD00144D with permission from the Royal Society of Chemistry. |
After a coffee break, the session on Analytical SERS resumed with Prof. S. Bell (Queen's University Belfast, UK) who presented exciting work on the quantitative detection of oligonucleotides using SERS (DOI: 10.1039/C7FD00134G). He showed that even though spectral changes when adding a single nucleotide to the 3′ terminus are small (Fig. 8), the signal-to-noise levels in these SERS spectra are low enough that difference spectra can be used to detect the nucleotide by comparing them with nucleobase reference spectra. Moreover, the SERS DNA chain signal is also influenced by the secondary structure (coiling) of the chain, an effect which was eliminated by thermal pre-treatment, which uncoils the chains. Dr G. Di Martino (University of Cambridge, UK) presented an exciting study into the optical response of individual nm-wide plasmonic nanocavities, created by fabricating nanoparticle-on-mirror geometry (NPoM) inside an electrochemical cell (DOI: 10.1039/C7FD00130D, see Fig. 9). She showed that the SERS response (peak intensity, resonance full width at half maximum (FWHM), and the spectral position of the coupled plasmon mode) is influenced by the bias voltage and discussed four scenarios which potentially induce these changes. The scenarios are ion penetration into the SAM, the potential driven movement of the double layer changing the local refractive index, electronic coulombic scattering from individual ionic charges in the double layer, and H2 gas formation around the AuNP. Finally, J. Guicheteau (RDECOM Edgewood Chemical Biological Center, USA) discussed the influence of various synthesis protocols on SERS enhancement, as well as the role of thermodynamics during substrate formation (DOI: 10.1039/C7FD00141J). The protocols were drop and dry on a substrate, leave the substrate in solution for a constant time and volume, and immerse until equilibrium is reached. To express the advantage of SERS over normal Raman sensing for a given protocol and analyte, a figure of merit termed the SERS enhancement value (SEV) was proposed.
Fig. 8 Prof. S. Bell speaks in the fourth session: Analytical SERS. Graphs: raw SERS spectra of ODN sequences showing the effect of adding nucleobases at the 3′ end on the spectra. Adapted from DOI: 10.1039/C7FD00134G with permission from the Royal Society of Chemistry. |
Fig. 9 Left panel: Optically transparent thin (sub-mm) electrochemical cell for spectroscopy of single Au NPs on molecular layer on Au. Right panel: SERS intensity time evolution under an applied voltage of 0 V (black) to −1.2 V (blue). Adapted from DOI: 10.1039/C7FD00130D with permission from The Royal Society of Chemistry. |
Chair of the session Prof. J. Popp (Leibniz-IPHT, Germany) gave his perspective on Analytical SERS: “The key for moving SERS into routine analytics is to improve the reproducibility of nanostructured SERS surfaces as well as the ability to perform quantitative SERS analysis. In this context, shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) will be an important step towards the reproducible characterization of the chemical composition of surfaces having inorganic, organic or biological origins. The quantification of analyte molecules can be significantly improved by employing internal standards to address variations in the SERS activity. Moreover, the direct label-free SERS method is best suited for the analysis/detection of low-molecular weight substances with high affinity toward the metallic surface. Thus, an intrinsic sample preparation step is included to enrich molecules with high affinity from complex matrices such as environmental samples or human body fluids. To detect molecules with less affinity toward silver or gold surfaces, the design of special recognition molecules changing their Raman signal while interacting with the analyte of interest due to conformational changes will be the solution. Finally, medical and in vivo SERS applications via smart SERS tags modified with antibodies or aptamers allowing for a specific interaction of biomarkers to detect e.g. tumour cells in blood or tissue will be an important SERS topic within the next years.”
Several themes recurred in all four sessions (Fig. 10). First, the use of the NPoM geometry as a versatile platform for SERS was present transversally in all of the sessions. Examples include opto-mechanics studies in NPoM geometry (Prof. J. Aizpurua) in session 1, dynamic heterogeneity on account of molecular motion inside the hot spots (Prof. K. Willets) in session 2, NPoMs of weakly and strongly SERS-active materials (Prof. Z. Q. Tian) and NPoM in electrochemical cells (Dr G. Di Martino) in session 4. Tip-enhanced Raman Spectroscopy or TERS frequently recurred as a versatile platform as well, sparking a discussion on whether (coupled) plasmons on the tip of a TERS probe are affected by the tip's shape. Prof. R. Van Duyne pinpointed the advantage of TERS in his opening lecture as “TERS combines the sensitivity of Raman with the spatial resolution of AFM/STM”. Finally, the chemical and plasmonic contributions to SERS signals were another recurring point of interest (e.g. Prof. S. Reich).
Also in this session, Prof. D. Graham pinpointed important future directions of the field as the “design and use of alternatives to plasmonic materials for enhancement and a move to quantitative SERS for meaningful applications where other techniques such as fluorescence fail, e.g. bioanalysis.”
Another excellent opportunity to network was incorporated into the programme in the form of the Conference Dinner. The delegates enjoyed a delicious three-course meal on Thursday night at the Supper Club, close to George Square. Prof. E. Campbell gave a formidable speech on her experiences as the president of the Faraday Society and in particular during the current Faraday Discussion. She also conferred the poster prizes, with Mr W. Lum (University of Cincinnati, USA) winning first prize (Fig. 11c) and the runners up being Mr N. Bontempi (University of Brescia, Italy) and Mrs R. Kidd (University of Southampton, UK). As is tradition, the dinner was closed with the Loving Cup ceremony (Fig. 11d). This silver cup, which dates back to 1728 and was crafted by lady silversmith Heslie Fawdery, is used to commemorate G. S. Marlow (Secretary and Editor, 1928–1947) and Angela & Tony Fish (Angela organised the Faraday Discussions 1968–1995). The ceremony involves taking a sip and passing the cup along via an intricate series of bows, which led to the occasional head bump.
The 2017 Faraday Discussion on SERS has been a vibrant and stimulating meeting. Its success was obvious during the discussion sessions, through the abundance of questions and remarks (more than 60 per session!), which often forced the session chairs to conclude the discussions prematurely due to time restrictions.
Footnote |
† All authors contributed equally. |
This journal is © The Royal Society of Chemistry 2017 |