Surface-Enhanced Raman Spectroscopy for Bioanalysis and Diagnosis
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Showcasing the Surface-enhanced Raman Spectroscopy (SERS) technique for Bioanalysis and Diagnosis As featured in: applications by a group of researchers led by Prof Liwu Volume 13 Number 27 21 July 2021 Zhang from Fudan University and Prof Ventsislav Valev Pages 11581-12046 from the University of Bath. Nanoscale rsc.li/nanoscale Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis SERS is an eff ective analytical technique that has excellent potential in bioanalysis and diagnosis as demonstrated by its increasing applications in vivo . SERS fi nds a broad range of applications with clinical relevance, such as biological ISSN 2040-3372 PAPER Shifeng Zhao et al. The sign reversal of anomalous Hall eff ect derived from the transformation of scattering eff ect in cluster-assembled sensing, drug delivery, single cell assays, early stage cancer Ni 0.8 Fe 0.2 nanostructural fi lms screening and fast detection of pathogens. We present a comprehensive survey of SERS-based assays, from basic See Nicoleta E. Dina , Ventsislav K. considerations to bioanalytical applications. Valev, Liwu Zhang et al. , Nanoscale , 2021, 13 , 11593. rsc.li/nanoscale Registered charity number: 207890 Nanoscale View Article Online REVIEW View Journal | View Issue Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis Cite this: Nanoscale, 2021, 13, 11593 Muhammad Ali Tahir,†a Nicoleta E. Dina, *†b Hanyun Cheng,a Ventsislav K. Valev *c and Liwu Zhang *a,d In recent years, bioanalytical surface-enhanced Raman spectroscopy (SERS) has blossomed into a fast- growing research area. Owing to its high sensitivity and outstanding multiplexing ability, SERS is an effective analytical technique that has excellent potential in bioanalysis and diagnosis, as demonstrated by its increasing applications in vivo. SERS allows the rapid detection of molecular species based on direct and indirect strategies. Because it benefits from the tunable surface properties of nanostructures, it finds a broad range of applications with clinical relevance, such as biological sensing, drug delivery and live cell imaging assays. Of particular interest are early-stage-cancer detection and the fast detection of patho- gens. Here, we present a comprehensive survey of SERS-based assays, from basic considerations to bio- Creative Commons Attribution 3.0 Unported Licence. analytical applications. Our main focus is on SERS-based pathogen detection methods as point-of-care Received 2nd February 2021, solutions for early bacterial infection detection and chronic disease diagnosis. Additionally, various prom- Accepted 2nd June 2021 ising in vivo applications of SERS are surveyed. Furthermore, we provide a brief outlook of recent endea- DOI: 10.1039/d1nr00708d vours and we discuss future prospects and limitations for SERS, as a reliable approach for rapid and sensi- rsc.li/nanoscale tive bioanalysis and diagnosis. 1. Introduction mass spectrometry, etc. that are developed for biomolecule detection and biomedical imaging, based on biological, physi- This article is licensed under a In applied sciences, rapid, accurate and sensitive response are cal and chemical phenomena. However, these tools are time key aspects of all analytical techniques; this is especially true consuming, they need favourable conditions for analysis and when it comes to detection and therapeutic issues within the expensive protocols, and sometimes they can struggle to solve Open Access Article. Published on 06 July 2021. Downloaded 10/10/2021 7:50:35 AM. healthcare environment. For reliable disease diagnosis and real-life practical issues (e.g. being unable to discriminate quick therapeutic actions, it is mandatory to have a clear between live and dead pathogens). For public health safety understanding of biological pathways and processes. and disease prevention, there is a dire need for detection Moreover, it is essential to have specific and ultrasensitive methods that offer high sensitivity, reproducibility, fast sample analytical tools for identifying clinically relevant molecular preparation time, user-friendliness and cost-effectiveness. This species. Traditional methods for bioanalysis and disease diag- need covers a wide range of biomedical applications including nosis are time consuming, as they require series of biochemi- vibrational spectroscopy for pathologies with reliable, fit-to- cal tests. Such delay is incompatible with medical emergen- purposes methods for bioanalysis and diagnosis. cies. Currently, there are different analytical tools, such as Benefiting from the recent advancements in optics, laser fluorescence immunoassay, enzyme-linked immunosorbent technology and nano-devices, surface-enhanced Raman scat- assay (ELISA), radio immunoassay, fluorescence spectroscopy, tering (SERS) has become a widely used spectroscopic tech- nique. The reasons are very straightforward: it can provide – structural information at the single-molecule level1 4 owing to a Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, the extremely large electromagnetic field amplification that is Department of Environmental Science & Engineering, Fudan University, Shanghai, produced by the excitation of localized surface plasmons 200433, Peoples’ Republic of China. E-mail: [email protected] bDepartment of Molecular and Biomolecular Physics, National Institute for Research (LSPs). Moreover, SERS is non-invasive, oblivious to water and Development of Isotopic and Molecular Technologies, 67-103 Donat, 400293 (omnipresent in biological samples) and can probe confor- Cluj-Napoca, Romania. E-mail: [email protected] mational changes, as it provides vibrational information on c Centre for Photonics and Photonic Materials, Department of Physics, University of the targeted bioanalytes.5 Several reviews show the potential of Bath, Bath, BA2 7AY, UK. E-mail: [email protected] SERS in therapeutic drug monitoring (TDM),6 in detecting dShanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, 7 Peoples’ Republic of China cancer cells and tumor margins in vivo conditions or in DNA 8 †These authors contributed equally to this study. biosensing. SERS could replace standard methods that are This journal is © The Royal Society of Chemistry 2021 Nanoscale,2021,13, 11593–11634 | 11593 View Article Online Review Nanoscale currently routinely used for DNA-based diagnosis. The possi- that are adsorbed on the surface of nanostructured metals, – bility to enhance disease diagnosis by employing SERS-based such as gold or silver nanoparticles (NPs).11 13 SERS also offers applications to detect biological markers at trace levels was structural information in biological media in ambient environ- evaluated recently in a comprehensive review by Chisanga ments.14 SERS surface selection rules mandate that the inten- et al.9 The current requirements of point-of-care (PoC) biosen- sity from vibrational modes perpendicular to the surface is sing, during an outbreak of a very contagious virus, are related increased while maintaining that from the parallel modes more than ever to strict biosafety regulations when transport- constant.12,15 Several environmental parameters, such as pH ing patients or biological samples to laboratory premises. The or temperature, can affect the surface adsorption of the bio- safe choice of portable handheld Raman devices with minia- analytes, and thus can influence also their spectral turized, reproducible enhancing substrates as sample support fingerprint.16 is becoming increasingly necessary. In practice, rapid Importantly, SERS is user-friendly, compared with other sampling, on a large scale, as a daily routine is met by the highly sensitive techniques (such as mass spectrometry), and amplified Raman signals, provided by SERS, which facilitate is applicable to aqueous solutions without the need for fast trace analysis of clinically relevant biomolecules in complex sample preparation protocols. Overall, SERS is quickly ambient conditions, involving minor sample preparation. For becoming an analytical technique of choice for successful instance, SERS-based detection of bacteria is fast and can be applications in bioanalysis, disease detection and performed at the single-cell level. It could be used for diagnos- diagnosis.9,17 Furthermore, SERS enables disease diagnosis ing human infections (e.g. with antibiotic-resistant bacteria) in vivo, i.e. inside living organisms, after coating biocompatible using culture-free methods, directly from patient fluids or even SERS-active NPs or substrates with appropriate surfactants in vivo.10 SERS also benefits from recent efforts to develop and/or protective shells.18 Fig. 1 presents representative tandem microfluidic devices in order to improve in situ bioa- examples of SERS-based bioassays reported in previous litera- nalysis with direct clinical applicability.7 ture for detecting bioanalytes directly or via specific receptors, Creative Commons Attribution 3.0 Unported Licence. SERS is regarded as an ultrasensitive technique because it aptamers, etc. The versatility of SERS-based detection tech- can achieve single-molecule (SM) detection. In large part, this niques is highlighted by showing different SERS substrates sensitivity is due to the enhancement (by factors up to 108 or designed for detecting whole cells or clinically relevant bioana- even larger) of inelastic light scattering by those molecules lytes with precise accuracy and high sensitivity. This article is licensed under a Open Access Article. Published on 06 July 2021. Downloaded