The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.

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Present and Future of Surface-Enhanced Raman Scattering

Taking advantage of exceptional attributes, such as being easy-to-operate, economical, sensitive, portable, and simple-to-construct, in recent decades, considerable attention has been devoted to the integration of recognition elements with electronic elements to develop electrochemical sensors and biosensors.Various electrochemical devices, such as amperometric sensors, electrochemical impedance sensors, and electrochemical luminescence sensors as well as photoelectrochemical sensors, provide wide applications in the detection of chemical and biological targets in terms of electrochemical change of electrode interfaces.

With remarkable achievements in nanotechnology and nanoscience, nanomaterial-based electrochemical signal amplifications have great potential of improving both sensitivity and selectivity for electrochemical sensors and biosensors. First of all, it is well-known that the electrode materials play a critical role in the construction of high-performance electrochemical sensing platforms for detecting target molecules through various analytical principles. Furthermore, in addition to electrode materials, functional nanomaterials can not only produce a synergic effect among catalytic activity, conductivity, and biocompatibility to accelerate the signal transduction but also amplify biorecognition events with specifically designed signal tags, leading to highly sensitive biosensing. Significantly, extensive research on the construction of functional electrode materials, coupled with numerous electrochemical methods, is advancing the wide application of electrochemical devices. For example, Walcarius et al. highlighted the recent advances of nano-objects and nanoengineered and/or nanostructured materials for the rational design of biofunctionalized electrodes and related (bio)sensing systems.1 The attractiveness of such nanomaterials relies on their ability to act as effective immobilization matrices and their intrinsic and unique features as described above. These features combined with the functioning of biomolecules contribute to the improvement of bioelectrode performance in terms of sensitivity and specificity. Our group recently presented a general overview of nanomaterial-enhanced paper-based biosensors including lateral-flow test-strip and paper microfluidic devices.2 With different kinds of nanoparticles (NPs), paper-based biosensor devices have shown a great potential in the enhancement of sensitivity and specificity of disease diagnosis in developing countries.

This Review focuses on recent advances in electrochemical sensors and biosensors based on nanomaterials and nanostructures during 2013 to 2014. The aim of this effort is to provide the reader with a clear and concise view of new advances in areas ranging from electrode engineering, strategies for electrochemical signal amplification, and novel electroanalytical techniques used in the miniaturization and integration of the sensors. Moreover, the authors have attempted to highlight areas of the latest and significant development of enhanced electrochemical nanosensors and nanobiosensors that inspire broader interests across various disciplines. Electrochemical sensors for small molecules, enzyme-based biosensors, genosensors, immunosensors, and cytosensors are reviewed herein (Figure ​(Figure1).1). Such novel advances are important for the development of electrochemical sensors that open up new avenues and methods for future research. We recommend readers interested in the general principles of electrochemical sensors and electrochemical methods to refer to other excellent literature for a broad scope in this area.3,4 However, due to the explosion of publications in this active field, we do not claim that this Review includes all of the published works in the past two years and we apologize to the authors of excellent work, which is unintentionally left out.



Figure 1

Schematic illustration of electrochemical sensors and biosensors based on nanomaterials and nanostructures, in which electrochemical sensors for small molecular, enzyme-based biosensors, genosensors, immunosensors, and cytosensors are demonstrated.

http://pubs.acs.org/doi/pdf/10.1021/ac5039863

Electrochemical Sensors and Biosensors Based on Nanomaterials and Nanostructures

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.

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

1.1. Significance of IVDs in the Clinic
IVD test is a crucial component of clinical care that performs a diagnostic test on biological samples that have been taken from a living body, such as blood, urine, and tissue.1 Such tests are usually performed to determine or confirm the presence of disease in an individual. “In vitro” literally means “within the glass”, which indicates that the test was historically conducted in glass test tubes. In contrast, in vivo tests, literally “within the living”, are conducted within a whole, living organism including human body.2 IVD tests have received much public attention because of their distinct features in the medical profession. First, IVD tests do not interact with the human body directly, making such diagnosis accessible without invasive surgeries and thus saving a great deal of suffering. Second, the procedures of IVDs are performed on samples rather than human body, avoiding the possible biological safety problems on patients that often take place in the in vivo diagnostics. Third, an IVD test can quickly provide valuable information on a patient’s healthcare conditions. On the basis of the information, physicians or patients are able to make a timely decision for patient care or treatment. Fourth, the application of IVDs enables early diagnosis and makes treatment of serious diseases easier. Generally, the cost of early testing is much lower than that of the later on extensive treatment. Last, IVDs play a particularly vital role in remote settings for managing outbreaks of acute infectious diseases, where effective but simple diagnostic systems are highly desirable. These features make IVDs unique and of great importance among medical technologies.

Gold Nanoparticles for In Vitro Diagnostics

Understanding the control of the optical and plasmonic properties of unique nanosystems--gold nanostars--both experimentally and theoretically permits superior design and fabrication for biomedical applications. Here, we present a new, surfactant-free synthesis method of biocompatible gold nanostars with adjustable geometry such that the plasmon band can be tuned into the near-infrared region 'tissue diagnostic window', which is most suitable for in vivo imaging. Theoretical modelling was performed for multiple-branched 3D nanostars and yielded absorption spectra in good agreement with experimental results. The plasmon band shift was attributed to variations in branch aspect ratio, and the plasmon band intensifies with increasing branch number, branch length, and overall star size. Nanostars showed an extremely strong two-photon photoluminescence (TPL) process. The TPL imaging of wheat-germ agglutinin (WGA) functionalized nanostars on BT549 breast cancer cells and of PEGylated nanostars circulating in the vasculature, examined through a dorsal window chamber in vivo in laboratory mouse studies, demonstrated that gold nanostars can serve as an efficient contrast agent for biological imaging applications.

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Gold nanostars: surfactant-free synthesis, 3D modelling, and two-photon photoluminescence imaging.

A SERS active gold nanostar layer on the surface of ITO glass slip has been prepared by a low-cost electrostatically assisted APTES-functionalized surface-assembly method for SERS analysis. The two-dimensional morphology of the SERS substrate was examined by scanning electron microscopy. Comparative analysis revealed that the optical characteristics and SERS efficiency of these substrates varied as a function of nanostar morphology. It was found that the substrate assembled with the longest branches of nanostars generated the best SERS efficiency, whether the excitation source is 785 or 633 nm. The potential use of these substrates in detection applications was also investigated by using Nile blue A and Rhodamine 6G. The detection limits are 5 × 10–11 M and 1 × 10–9 M, respectively, when using the 785 nm excitation source. Apart from this high enhancement effect, the substrate here also shows extremely good reproducibility at the same time. All of these indicate that gold nanostars are a very good structu...

A reproducible SERS substrate based on electrostatically assisted APTES-functionalized surface-assembly of gold nanostars.

Fabrication of large-scale gold nanoplate films as highly active SERS substrates for label-free DNA detection.

A novel label-free amperometric immunosensor for carcinoembryonic antigen based on Ag nanoparticle decorated infinite coordination polymer fibres.

In the present work, we have developed a novel nanocomposite-based method for estimating antioxidant activity. The assay implements a new enzyme-free optical nanoprobe for assessing hydrogen peroxide (H2O2) scavenging activity based on the formation process of gold nanoshells (GNSs). H2O2 could enlarge the gold nanoparticles (GNPs) on the surface of GNSs precursor nanocomposites (SiO2/GNPs), and the preadsorbed GNPs served as nucleation sites for Au deposition. As the concentration of H2O2 increases, more GNPs on the SiO2 cores are enlarged until continuous GNSs are formed. During the growth procedure, the spectra changes correlate well with H2O2 concentrations which indicate that this nanocomposite is a good nanoprobe for detecting H2O2. H2O2 scavenging activities of several antioxidants were determined by restraining the H2O2-mediated formation of GNSs from SiO2/GNPs, and the changes of the corresponding plasmon absorption bands correlated well with H2O2 scavenging activity of antioxidants. The spectra ...

Development of methodology based on the formation process of gold nanoshells for detecting hydrogen peroxide scavenging activity.

Large-scale synthesis of ultrathin Au-Pt nanowires assembled on thionine/graphene with high conductivity and sensitivity for electrochemical immunosensor

Jian Dong

Papers

A reproducible SERS substrate based on electrostatically assisted APTES-functionalized surface-assembly of gold nanostars.

Fabrication of large-scale gold nanoplate films as highly active SERS substrates for label-free DNA detection.

A novel label-free amperometric immunosensor for carcinoembryonic antigen based on Ag nanoparticle decorated infinite coordination polymer fibres.

Development of methodology based on the formation process of gold nanoshells for detecting hydrogen peroxide scavenging activity.

Large-scale synthesis of ultrathin Au-Pt nanowires assembled on thionine/graphene with high conductivity and sensitivity for electrochemical immunosensor