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Surface-enhanced Raman spectroscopy (SERS):

Cite this: J. Mater. Chem. C, 2018,
6, 5314
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an adventure from plasmonic metals to organic
semiconductors as SERS platforms
Gokhan Demirel, *a Hakan Usta, *b Mehmet Yilmaz,ac Merve Celik,d
Husniye Ardic Alidagibe and Fatih Buyukserind

The quantitative determination and identification of bio-/chemical molecules at ultra-low concen-

Received 9th March 2018,
Accepted 23rd April 2018
DOI: 10.1039/c8tc01168k
rsc.li/materials-c
trations is a hot topic in several fields including medical diagnostics, environmental science, and homeland
security. Molecular detection techniques are conventionally based on optical, electrochemical, electronic, or
gravimetric methodologies. Among these methods, surface-enhanced Raman spectroscopy (SERS) is
considered as one of the most reliable, sensitive and selective techniques for non-destructive molecular
analysis through the amplification of electromagnetic fields and/or creation of charge-transfer states
between the chemisorbed analyte molecule and SERS active platform. Unfortunately, the applicability of
SERS is rather limited, which is mainly due to the lack of highly sensitive SERS platforms with good stability
and reproducibility. In line with this, metal nanoparticles (e.g., Au, Ag, and Cu) have been extensively
exploited as SERS active platforms. Although the utilization of metallic nanoparticles in SERS is simple and
cost-effective, the poor controllability of the structures and limited formation of hot spots in the detection
zone leads to discrepancy in the resulting SERS signals. For these reasons, in the past few years, researchers
have focused on fabricating 3-dimensional (3D) SERS platforms, which increase the adsorption of analyte
molecules and facilitate hot spot formation in all three dimensions. However, the fabrication of 3D SERS
platforms is mostly expensive and technologically demanding. Therefore, the discovery of non-metal
alternative approaches is of great interest not only to widen SERS applications but to further elucidate
fundamental questions. Considering recent developments on the fabrication and application of SERS active
platforms, this review is structured in 3 main directions; (1) implementation of the plasmonic nanoparticles
having different shapes into SERS-active platforms, (2) highlighting recent developments in the fabrication
and application of 3D SERS-active platforms, and (3) examination of recent novel inorganic and organic
semiconductor based platforms for SERS applications. At the end, we conclude with the promises and
challenges for the future evolution of SERS.

Introduction
Surface-enhanced Raman spectroscopy (SERS) is a promising
analytical tool providing sensitive, selective and non-destructive
bio-/chemical information, which is highly desirable in several
fields such as medical diagnostics,1,2 environmental protection,3
food safety,4 and homeland security.5 Therefore, during the last
a
Bio-inspired Materials Research Laboratory (BIMREL), Department of Chemistry,
Gazi University, Ankara, 06500, Turkey. E-mail: nanobiotechnology@gmail.com
b
Department of Materials Science and Nanotechnology Engineering,
Abdullah Gül University, Kayseri, 38080, Turkey. E-mail: hakan.usta@agu.edu.tr
c
Department of Bioengineering, Faculty of Engineering and Architecture,
Sinop University, Sinop, 57000, Turkey
d
Department of Biomedical Engineering, TOBB University of Economics and
Technology, Ankara, 06560, Turkey
e
Department of Chemistry, Gebze Technical University, Kocaeli, 41400, Turkey
decade, there has been increasing interest not only in developing
novel SERS-active materials but also in improving its utilization
in real life applications. Fundamentally, Raman spectroscopy is
based on inelastic scattering of a photon by molecules, which was
first theoretically proposed by Smekal in 19236 and experimentally
observed by Raman and Krishnan in 1928.7 In this scattering
process, vibrational or rotational modes of molecules are excited
or relaxed leading to a change in wavelength of the photons. Since
each chemical species possesses varying characteristic vibrational
energy levels, in theory, a fingerprint Raman spectrum may be
collected for every molecule. Unfortunately, the applicability of
conventional Raman spectroscopy is rather limited because it has
a very low scattering cross section (B1029–1030 cm2 per molecule)
in comparison to other spectroscopic techniques such as UV
(B1018 cm2 per molecule), IR (B1021 cm2 per molecule) and
fluorescence (B1024–1014 cm2 per molecule).8 Therefore, from

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Review
an application point of view Raman spectroscopy has not drawn
enough interest for quite a long time.
Feischmann, Hendra and McQuillan in 1974 surprisingly
identified intense Raman signals from pyridine molecules placed
onto a roughened silver surface.9 To explain this observation,
they first speculated that the observed large intensities in Raman
scattering were due to an increase in the number of adsorbed
pyridine molecules on the roughened surface. In 1977,
Jeanmaire, Van Duyne, Albercht, and Creighton independently
clarified the enhancement mechanism of pyridine molecules
adsorbed on a roughened silver surface, and proposed that
Raman signal enhancement is not simply explained by an
Published on 23 April 2018. Downloaded on 12/11/2018 8:46:16 AM.
Gokhan Demirel earned his BS
degree in Chemistry from Gazi
University (Ankara, Turkey) in
2000. He obtained his MSc and
PhD degrees at the same
department in 2003 and 2006,
respectively. After completing his
PhD, he became a postdoctoral
researcher in the bioengineering
division at Hacettepe University
from 2006 to 2007. Later he
worked at University College
Gokhan Demirel Cork and Pennsylvania State
University as a postdoctoral
fellow from 2007 to 2010. He is currently an Associate Professor
at Gazi University. He has published more than 70 research
articles, and his main research areas are bio-inspired materials,
functional thin films and their applications.
Mehmet Yilmaz received both
his BS and MS in chemical
engineering from Hacettepe
University and Ankara University
in 2005 and in 2009, respectively.
He obtained his PhD in the
Bioengineering Department at
Hacettepe University in 2014.
He worked as a post-doctoral
researcher from 2014 to 2017
under the guidance of Prof.
Gokhan Demirel (Gazi University,
Mehmet Yilmaz Turkey) and Prof. Nicholas A.
Kotov (University of Michigan,
USA). He is currently Assistant Professor at Sinop University and
focused on the synthesis and manipulation of chiral nanomaterials
and manufacture of nanostructured thin films, as well as their
applications in sensing (especially SERS applications), therapy and
bioimaging.
This journal is © The Royal Society of Chemistry 2018
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Journal of Materials Chemistry C
increase in the number of molecules. It was actually due to an
increase of the scattering cross-section for the adsorbed
molecules.10,11 Although there is still no consensus on the exact
Raman signal enhancement mechanism, today, two primary
theories called chemical enhancement and electromagnetic
enhancement are widely accepted.12–16 Among these theories,
the major contribution to Raman signal enhancement is origi-
nated from an electromagnetic (EM) mechanism. The EM
enhancement is largely based on the electrical field magnifica-
tion through excitation of localized surface plasmon resonances
of the underlying SERS-active platform. However, in order to
obtain enhanced scattering, the perpendicular orientation of
Hakan Usta received his BS in
Chemistry in 2004 from Bilkent
University (Ankara, Turkey) and
obtained his PhD in Chemistry
from Northwestern University
(Evanston, IL) under the super-
vision of Prof. Tobin J. Marks in
2008. He then joined Polyera
Corporation (Skokie, IL), where
he worked in Senior Research
Scientist and Project Leader
positions between 2008 and
Hakan Usta 2013. He is an Associate
Professor in the Department of
Materials Science and Nanotechnology Engineering at Abdullah
Gül University. He has published more than 50 research articles,
has 2 book chapters, and holds 13 international patents. His
current research interests include the design and development of
functional organic materials for optoelectronic and spectroscopic
applications.
Merve Celik obtained her BS
degree in biomedical engineering
from Bas- kent University in 2015.
After earning her MSc. degree, she
is continuing her PhD education
at TOBB University of Economics
and Technology in biomedical
engineering program. Her current
areas of interest are optical
sensors, surface-enhanced Raman
spectroscopy and biosensor
platforms.
Merve Celik
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Journal of Materials Chemistry C
plasmon oscillations to the SERS active surface is a necessary
condition.15,17–19 In the case of in-plane oscillation (along the
surface), there would be no enhanced scattering (only adsorption
takes place). Therefore, surfaces having appropriate roughness
are mostly needed for enhanced scattering. Although the EM
theory provides information on the origin of the enhancement
in Raman scattering, unfortunately, it does not fully clarify
the magnitude of the observed enhancements. The chemical
enhancement (CE) theory, in this context, provides a different
perspective on the Raman scattering enhancement. This theory
mainly involves the creation of charge-transfer states between the
chemisorbed molecule and Raman active platform. These energe-
tically favorable states provide a pathway for resonant excitation,
which in turn, increases the probability of a Raman transition.12–14
However, the generation of charge-transfer states depends on the
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energy levels of the analyte molecules and Raman active platforms.
Therefore, selection and/or fabrication of appropriate platforms
that provide effective Raman signal enhancement is very critical
to SERS.
This review intends to provide an overview of the recent
developments on the fabrication and application of novel SERS-
active platforms. Since a series of comprehensive review articles
has already covered in-depth discussion of the enhancement
mechanisms in SERS,12–16 no detailed attempt is made here.
This review is structured based on the recent implementations
of three main material types into novel SERS-active platforms;
(1) plasmonic nanoparticles with varied shapes, (2) 3D hybrid
structures, and (3) (in)organic semiconductor micro-/nano-
structures. At the end, we conclude with the promises and
challenges for the future progress of SERS.
1. Metal nanoparticle-based SERS platforms
Since the electromagnetic enhancement mechanism is the
main contributor to the Raman signal enhancement, noble
Husniye Ardic Alidagi earned her
BS degree in chemistry from
Yıldız Technical University in
2006. She received her MSc and
PhD degrees in chemistry at
Gebze Technical University in
2009 and 2016, respectively. She
is currently a post-doctoral
researcher in Materials Science
and Nanotechnology Engineering
Department at Abdullah Gul
University. She has also been a
Husniye Ardic Alidagi research assistant at Gebze
Technical University since 2009.
Her research is mainly focused on phosphazene chemistry,
conjugated systems, dendrimers, molecule based chemical
sensors, and organic thin-film transistors (OTFTs).
5316 | J. Mater. Chem. C, 2018, 6, 5314--5335
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metal nanoparticles with plasmonic features have extensively
been exploited as SERS platforms mainly due to their simplicity
of fabrication.20 The most commonly employed and well-
established method for preparing metallic nanoparticles is
the reduction of metal cations from their salts.21,22 For example,
silver colloids can be prepared by the method that Lee and
Meisel22 proposed, which involves the reduction of silver nitrate
using NaBH4. Gold colloids, on the other hand, can simply be
synthesized through the reduction of chloroauric acid by citrate,
known as the Turkevich method.23 Additionally, copper nano-
particles can also be used occasionally as SERS platforms but they
are found to be less effective compared to gold and silver.24 The
flexibility in the manipulation of the particle fabrication process
including temperature, reactant concentrations, and ionic
strength enables the adjustment of parameters such as size,
shape, interparticle distance, aggregation properties, and surface
charge properties which should be considered for SERS
efficiency.25 Both theoretical and experimental results demon-
strate the importance of particle shape and size on their
plasmonic properties.26 To date, various methods for synthesizing
nanostructures with different morphologies including nano-
rods,27,28 nanotriangles,29,30 nanocubes,31,32 and nanocages,33,34
have been suggested for the fabrication of SERS-active platforms.
Further enhancement with increased sharpness and roughness
could be achieved by developing nanoflowers,35,36 nanostars,37,38
and other structures with higher curvature (i.e., nanohydrangea
flower39). The dense and enhanced plasmonic hot spots in
sharp edges and nanogaps drastically increase the surrounding
electrical field, enabling even a single molecule level detection.39
For example, Matteini and co-workers demonstrated a method for
the detection of proteins through gold concave nanocubes
(CNCs).40 In this work, the CNCs were fabricated by a seed-
mediated synthetic method and B130 nm-sized particles with
six concave faces were obtained (Fig. 1a). Taking advantage of
Fatih Buyukserin graduated from
Bilkent University Chemistry
Department and then completed
his PhD under the supervision of
Prof. Dr Charles R. Martin at
University of Florida. He then
studied at University of Texas
Southwestern Medical School at
Dallas as a postdoctoral research
associate with Prof. Dr Jinming
Gao. He moved back to Gazi
University Nanomedicine Research
Fatih Buyukserin Center in 2009, and then finally
joined the Biomedical Engineering
Department of TOBB University of Economics and Technology. He is
currently an Associate Professor at this department and adjunct
faculty of the Materials Science and Engineering Department of the
same university. His research interests are membrane science,
biosensors, nanomedicine, targeted delivery and biomaterials.
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Fig. 1 (a) TEM image of a gold concave nanocube (CNC) array. (b) Representative SERS spectra of cytochrome c and insulin using CNC arrays under
639 nm Raman laser excitation. (c) The schematic representation of the expected SERS hot spot formation in which the protein (cytochrome c in the
example) is entrapped in a hole between CNCs.40 Published by the Royal Society of Chemistry.
the water repelling nature of polydimethylsiloxane (PDMS) film,
which was used to support the CNCs, analyte proteins were
trapped into CNC arrays (Fig. 1c). In this way, the authors were
able to detect biomolecules including cytochrome c and insulin
using the fabricated SERS active platforms (Fig. 1b).
Bimetallic nanoparticles, which consist of two different
metals, offer superior advantages compared to their mono-
metallic counterparts for SERS applications. Among the various
types of bimetallic structures, nanoparticles containing Au and
Ag have particularly attracted great attention, and they have
been fabricated in various shapes, sizes, and structures.41,42
Although such Ag@Au bimetallic structures could not reach the
enhancements achieved with monometallic Ag nanoparticles,
they induce an obvious enhancement in the SERS signals
compared to monometallic Au nanoparticles.43 Being able to
perform surface modification through chemisorption of struc-
turally varied ligands is another advantage of the metal nano-
particles which are used in SERS applications.44 Incorporation
of Raman-active molecules (SERS nanotags) into the nano-
particles further enhances the Raman signal intensity. Due to
the unique optical properties, the Raman signal from adsorbed
reporter molecules can be increased by up to 1014 or 1015,
allowing single molecular level detection.45 This strategy does
not only provide enhancement of the detected signal, but also
contributes to concentration of the analyte of interest around
the SERS probe. In line with this, Liz-Marzan and co-workers
recently published a report on multiplex imaging and detection
of cells using Raman reporter encoded gold nanostars that were
able to distinguish five different types of breast cancer cells.46
Recently, aptamer-modified metallic nanoparticles have also
been employed in SERS-based selective and sensitive molecular
detection. For example, Zhao and co-workers have reported an
aptamer-modified SERS active Au nanoflower (NF)–Ag nano-
particle (NP) core–satellite assembly for the detection of
microcystin-LR (MC-LR) toxin (Fig. 2).47 Herein, the molecular
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probes (aptamers) do not only induce the formation of the
hybrid nanoparticles, but also ensure a short interparticle
distance (B4 nm) between NFs and NPs enabling high SERS
efficiency. The limit of detection for MC-LR was found to be
0.01 nM, which is 100 times lower than the maximum allowable
concentration of MC-LR in drinking water. Instead of using
molecular probes, different chemical components as amplification
intermediates have also been utilized for the SERS-based indirect
detection of some important biomolecules.48 In this context, Fu
and co-workers have demonstrated a SERS sensor to detect the
glucose level in human serum through the silver-ion-mediated
amplification approach.49 In their work, 4-aminothiophenol mole-
cules were assembled on gold wafers and cysteamine modified
silver nanoparticles were used as SERS enhancement components.
In the presence of glucose with glucose oxidase enzyme, hydrogen
peroxide was produced which etches silver nanoparticles to Ag+.
These ions serve as agents connecting the cysteamine conjugated
silver nanoparticles to the 4-aminothiophenol functionalized
gold wafer. When the glucose concentration was increased in
the medium, more Ag+ ions were produced and, therefore, this
leads to enhanced Raman signal intensities up to 105. The
authors demonstrated a good linear relation between the SERS
intensity and glucose concentration in human serum from
0.5 mM to 8 mM.
Besides the incorporation of the nanoparticles with the
analytes, a different strategy was developed to detect targets
in cellular or microorganism environments. Intracellularly
grown metal nanoparticles are commonly employed for the
imaging and detection of cells rather than passive uptake. It has
already been shown that some microorganisms have the ability
to reduce metal ions to form metallic nanoparticles.50 This
capability of microorganisms has been also shown for human
cells as well.51 In this way, conventional problems such as over-
aggregation, uneven distribution and low efficiency of nano-
particles could be overcome. For example, Chen et al. proposed
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Fig. 2 (a) Schematic representation of the gold nanoflower (Au NF)–silver nanoparticle (Ag NP) SERS-active core–satellite platforms for the detection of
MC-LR. (b) TEM images of Au NF–Ag NP core–satellite platforms in the presence of varying concentrations of MC-LR. (A–E) 0, 0.05, 0.5, 5.0, and
10.0 nM, respectively. (F) Control (a mixture of Au NFs and Ag NPs). (c) (A) Representative SERS spectra of 4-NTP, 4-NTP modified Ag NPs and Au NFs, and
Au NF–Ag NP core–satellite platforms. (B) SERS spectra of Au NF–Ag NP core–satellite platforms in the presence of different concentrations of MC-LR
solution. (C) The standard curve between the Raman signals at 1330 cm1 and the concentration of MC-LR.47 Published by the Royal Society of
Chemistry.

a method for the detection of hemozoin in malaria infected
human blood by SERS.52 They demonstrated that growing nano-
particles inside the parasite results in higher SERS intensities
than that of mixing nanoparticles with the analyte. In their work,
the limit of detection was found to be 0.00005% for silver
nanoparticles synthesized inside the cells, whereas the detection
level was 0.01% for nanoparticles synthesized separately before
mixing with the samples.
Despite the recent progress in the field of nanoparticle
based SERS, materials (i.e., Au, Ag, or Cu) and morphology
(e.g., sphere, rod, and triangle) limitations remain a problem to
be overcome. In this respect, Tian’s group in 2010 demon-
strated an alternative Raman technique called shell-isolated
nanoparticle-enhanced Raman spectroscopy (SHINERS).53
Typically, a SHIN consists of a plasmonic core with a thin
(1–5 nm) layer of dielectric shell. The dielectric shell, which is
generally silica,53 alumina,53 manganese dioxide54 or graphene,55
does not only serve as a spacer between the plasmonic nano-
particles for generation of reproducible hotspots, but also
enhances the durability of the nanoparticles. The SHINERS
technique has been employed in various fields of science and
technology including biomedical research. For example, Zheng
and co-workers demonstrated the detection of microcalcification
and monitoring of local pathological states in breast tissue by
Au@SiO2 shell-isolated nanoparticles.56 The fabricated SHINs
were able to probe the presence of calcine deposits and
differentiate five different states of breast tissue. With the
developed decision algorithm, these nanoparticles allowed
detection of breast lesions with and without microcalcification
at 99.4% and 93.6% accuracy values, respectively.
In a different scheme, DNA origami–plasmonic nanoparticle
hybrids have recently been proposed as platforms with pre-
destinated orientation of nanoparticles for SERS applications.
The utilization of DNA origami in the fabrication of SERS active
platforms is a simple, cost effective and versatile approach to
increase the SERS efficiency. In 2016, Prinz et al., for the first
time, combined the DNA origami technique with SERS to detect
targets at a single molecule level.57 In their work, triangular
DNA origami structures were synthesized using the M13mp18
virus strand as a template for SERS active plasmonic particles.
After attachment of AuNPs to the DNA origami templates,
silver deposition was further carried out in order to adjust
the distance between the metallic nanoparticles and to enhance
the SERS signal of target molecules (i.e., TAMRA and Cy3).
Using this approach, they were able to detect TAMRA and Cy3 at
a single molecule level (Fig. 3).
Lately, combination of microfluidic devices and SERS has
gained increased attention.58,59 Compared with conventional
droplet-based methods, lab-on-a-chip SERS techniques can
achieve high sample throughputs. To this end, Wu et al.
reported a SERS-microfluidic device consisting of a silver-
coated gold nanorod decorated PDMS microchannel system
to detect thiocyanate (SCN) in human serum and saliva.60
In their work, SCN detection was attained in human serum
covering a widespread concentration range from 4 to 256 mM, and
the result obtained from human saliva was used to distinguish

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Fig. 3 (A) Schematic representation for the formation of AuNP dimers using DNA origami. (B) Experiments at the single molecule level. (a) AFM and
Raman measurements for platform 4a with two (dimer i, left) or only one (dimer ii, right) TAMRA molecule incorporated. (b) Analogue AFM and Raman
experiments to (a) by using Cy3 as the analyte molecule (platform 4b). (C) FDTD calculations revealing the distribution of the electro-magnetic field
enhancement for a single AuNP (top) and a dimer consisting of two AuNPs with a silver shell (below).57 Published by the Royal Society of Chemistry.

between smokers and non-smokers. Another report by Pallaoro
and co-workers showed the detection and identification of
individual mammalian cells with a SERS-microfluidic combined
system involving SERS biotags.61 The system was proven to
identify low-concentration cancerous cells from a population of
non-cancerous cells.
2. Three-dimensional plasmonic SERS platforms
The Raman signal obtained from a SERS-active platform is
largely originated from the generation of hot spots which are
created by gaps, sharp edges, or tips of nanostructures in
different shape or size. To date, most of the conventional
SERS-active platforms have been engineered mainly based on
1D or 2D materials. Although the utilization of such platforms
provides many advantages in SERS applications including low
cost, rapid fabrication, and ease of implementation, the poor
controllability of the structures and limited formation of
hot spots in the detection zone remain unaddressed issues
especially for the identification of small and non-resonant
molecules.62–64 For these reasons, in the past few years,
researchers have been focusing on the fabrication of 3D
SERS platforms which provide increased adsorption of target
molecules and enhanced hot spot formation in all three
dimensions.65–67 In low-dimensional geometries, hot-spots
are localized at specific points or in a single point. However,
in 3D SERS platforms, the laser confocal volume is a 3D space,
indicating full contribution from the 3D effective volume.68 The
effective volume of the 3D SERS platforms creates stronger
SERS response compared with low-dimensional substrates69
through increasing the average field enhancement and maxi-
mizing the generation and collection of SERS signals. Additionally,
for the case of 3D SERS platforms, the incident laser is not
required to be precisely focused on the confocal plane. These
striking advantages of 3D substrates give an impetus to
researchers to create new procedures for practical applications.
For the fabrication of 3D SERS platforms, two different

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approaches are commonly employed. In the first one, the sub-
strates with 3D morphologies are fabricated using a plasmon-
free inorganic or organic material based on various techniques,
including template-wetting,70 electrospinning,71 lithography,72
PVD,73 and so forth. The fabricated substrates are then modi-
fied with plasmonic nanoparticles or thin films and employed
as a SERS platform. Among various materials, utilization of
filter paper composed of 3D cellulose fiber networks as a 3D
template material for SERS applications is a simple, facile and
cheap approach. For example, Zheng et al. demonstrated a 3D
SERS platform based on simple dip-coating of filter paper into a
concentrated AuNP dispersion in an organic solvent.74 The
fabricated platforms exhibited excellent homogeneity, with a
10–15% intensity variation over a large area. In a similar way,
Jeong and co-workers have recently reported a plasmonic
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Another effective template material for SERS applications is
based on polymeric materials with 3D nano-/micro-morphologies.
In 2010, Demirel’s group demonstrated that 3D aligned, tilted
poly(chloro-p-xylene) (PPX) nanofiber arrays fabricated via oblique
angle polymerization could be employed as effective SERS
platforms when they were combined with a thin film of gold for
the detection of viral genes.76 In their work, the unique 3D
morphology of PPX decorated with a thin film of gold generates
hot spots with an extremely high electric field enhancement
(EF = B106). To examine the efficacy of their films as SERS sensor
platforms, they modified platforms with a molecular probe (MP),
which is a hairpin shape single stranded DNA having a dye and
thiol linker attached to the 3 0 - and 5 0 -ends. Analogous identifi-
cation of the hybridized and unhybridized forms of the MPs were
tested by SERS measurements of fluorophores. In the presence of

Schirmer strip for the determination of uric acid in human
tears (Fig. 4).75 In this work, the SERS strips were fabricated on
filter paper by thermally evaporating a thin gold film. They
demonstrated that the plasmonic Schirmer strips could be
employed for the fingerprint detection of uric acid even at a
25 mM concentration level.
genomic viral target against respiratory syncytial viruses (RSVs),
the fabricated platforms displayed a very low detection limit
(B1010 M) for the RSV target.
In addition to PPX nanofiber arrays, some elastomers such
as polydimethylsiloxane (PDMS) can also be employed to
fabricate 3D SERS platforms. For example, Kahraman et al.

Fig. 4 (a) Schematic illustration of a plasmonic Schirmer strip for SERS-based tear screening. (b) Representative top-view and (c) cross section SEM
images of the plasmonic Schirmer. (d) SERS spectra of uric acid in artificial tear solution. (e) SERS spectra obtained from human tears with varying uric acid
levels. (f) Uric acid level estimation in tears by comparing the SERS peak intensity ratios measured from human tears with those from the artificial tear
solution. Reproduced with permission from ref. 75. Copyright (2017) American Chemical Society.

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proposed the fabrication of a mechanically flexible plasmonic
nanostructure based on the combination of soft lithography
and thin silver film deposition.77,78 In these studies, they used
PDMS and regular arrays of self-assembled spherical sulfate
latex particles as a mold. The as-prepared silver-coated nano-
voids were employed as efficient SERS platforms (EF = 1.4 
106) for the detection of a Raman reporter molecule as well as
for the label-free SERS detection of different proteins at low
concentrations or for the capture of intact and ruptured
exosomes in solution. It was shown that 3D bowl-shaped
nanovoids provide strong SERS spectra with more features and
no background signals for different proteins such as bovine
serum albumin (BSA), hemoglobin, thrombin, avidin, cyto-
chrome c, and lysozyme. Alternatively, Focsan et al. reported a
similar strategy to create an enhanced SERS immunosensor
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based on a flexible 3D gold nanocup platform.79 They could
manipulate the plasmonic response of the platforms and
the resulting electromagnetic field enhancement by simply
changing the size of the polystyrene spheres. After proper
functionalization, flexible nanocup arrays were tested as an
immunosensor through human IgG as a recognition element
for the specific detection of the anti-human IgG. They reported
that this flexible nanosensor system could be a good candidate
for portable, inexpensive, label-free and real-time detection of
biomarkers with high sensitivity and specificity in diagnostic
applications.
Besides these approaches, the block copolymer lithography
technique was also considered as a facile way to fabricate 3D
SERS platforms. In line with this, Lee et al. developed 3D
nanostructures by combining block copolymer lithography
and imprinting techniques.63 The block copolymer lithography
approach served as a template for producing 3D structures
composed of fibers with sub-100 nm diameters. The imprinting
technique created cylindrical geometry for the local confine-
ment of the block copolymers. These two techniques resulted in
the production of 3D nanostructures within a cylindrical shape
in the form of an array on a substrate. These micro-cylinders
with nanofibers were transformed to nanoporous micro-
cylinders via oxygen plasma treatment. After oxygen treatment,
these highly porous 3D nanostructures were suitable for metal
nanoparticle deposition and producing a high density of hot
spots for SERS detection (EF = B105).
Another 3D template material for building a SERS platform
is vertically aligned silicon nanowire arrays (SiNWs).80,81
To date, various techniques have been employed to prepare
3D SiNW arrays including chemical vapor deposition (CVD),82
soft templating (ST),83 molecular beam epitaxy (MEB),84 oxide-
assisted growth (OAG),85 and metal-assisted chemical etching
(MACE).86 The features of SiNWs including their size,
diameters, and gaps between them can easily be controlled by
manipulating and optimizing the fabrication parameters,
which affect their analytical performances. For example, in
2008, Zhang et al. reported a large-area silver coated SiNW
array platform for SERS based sensing.87 In their work, they
fabricated SiNW arrays via the well-established MACE method,
and modified them with aminosilane molecules to immobilize
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Journal of Materials Chemistry C
small gold nanoparticles. To generate a highly SERS active
platform, gold decorated SiNWs were finally immersed into a
silver plating solution. In this way, they observed that the SERS
signal intensities obtained from the fabricated platforms
are about 8 fold higher than those obtained from alternative
platforms. In the same work, the feasibility of the fabricated
platforms as a SERS based sensor was also successfully tested
by using amoxicillin, an antibiotic, and calcium dipicolinate
(CaDPA), a biomarker for anthrax. Although the developed
silver-decorated SiNW arrays exhibited good SERS responses,
the fabrication of these platforms is time consuming and
requires multistep procedures. Moreover, undesired impurities
originating from the chemicals and solvents employed in the
fabrication process can cause serious problems against sensi-
tive and selective detection. Alternatively, in 2014, Demirel and
co-workers demonstrated a simple and effective strategy for the
fabrication of silver nanoparticle decorated SiNW arrays by
combining bio-inspired polydopamine coating and electroless
plating, which leads to the control of the density and morphology
for silver nanoparticles on SiNWs.88 The fabricated platforms
showed remarkable surface enhancement ability (4106) with high
reproducibility (lower than B10% spot-to-spot and sample-to-
sample variations). Furthermore, they demonstrated that the
PDOP coating not only serves as a reducing agent for the in situ
deposition of silver nanoparticles on SiNWs, but also contributes
to the SERS signal enhancement via improving photon scattering
and promoting electron transfer processes due to its organic
semiconductor nature. More recently, Li et al. reported a novel
strategy for the generation of effective SERS platforms composed
of free-standing SiNWs decorated with graphene-encapsulated
gold nanoparticles (Fig. 5).89 In their work, they fabricated SiNW
arrays via the CVD approach and decorated them with gold
nanoparticles through a galvanic deposition method. Finally, they
employed a xylene-based CVD method to encapsulate a multilayer
graphene shell on the gold nanoparticles. They reported that
the graphene encapsulation makes more uniform distribution
of ‘‘hot spots’’ in the heterostructures. Consequently, the fabri-
cated platforms exhibit good SERS signal enhancement up to 107
with a good reproducibility and uniformity. Recently, Wang et al.
also proposed a multifunctional SERS chip that can capture,
discriminate and inactivate pathogenic bacteria.90 In this work,
the SERS chip was prepared by chemical reduction assisted
etching and conjugation of 4-mercaptophenylboronic acid via
Ag–S bonds. This platform provided high sensitivity and specific
discrimination of E. coli and S. aureus from human blood. Some
remarkable data for this substrate can be summarized as follows:
enhancement factor of B107, relative standard deviation of
B11.0%, adaptable bacterial-capture efficiency of B60%, a low
detection limit of B1.0  102 cells per mL, and high antibacterial
activity of B97%.
As mentioned above, the 3D SERS platforms could also be
created directly using materials with plasmonic properties and
be used in SERS applications without further modifications.
Among many different techniques, self-assembly of colloidal
plasmonic particles into well-organized and ordered morphol-
ogies is considered as one of the simplest and most effective
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Fig. 5 (a) Representative SEM image of the graphene-encapsulated gold nanoparticles on SiNWs. (b) TEM image of a single graphene-encapsulated gold
nanoparticle on a SiNW. The inset demonstrates the evolution of partially emptied gold–graphene hollow tips. (c and d) High-resolution TEM images and
corresponding FFT revealing two representative local regions in image (b). (e and f) SERS spectra of 106 M R6G solution obtained from different
substrates under 785 nm (e) and 532 nm (f) laser excitations. The substrates include (1) annealed gold nanoparticles on flat Si substrates, (2) pristine SiNW
arrays, (3) SiNW–gold nanoparticle heterostructures, and (4) graphene-encapsulated gold nanoparticles on SiNW heterostructures.89 Published by the
Royal Society of Chemistry.

approaches toward the fabrication of 3D SERS platforms.91–94
Although plasmonic particles at the single particle level do not
exhibit desirable SERS response, their Raman signal enhance-
ment ability dramatically increases within assemblies due to
the homogenous distribution of hot spots with very high
density. For example, Alvarez-Puebla et al. reported highly
ordered supercrystal gold nanorod films for the detection of
scrambled prions through SERS.95 In their work, they fabricated
gold nanoros supercrystals based on the evaporation induced
self-assembly approach (EISA). The resultant organization of gold
nanorods into supercrystals provides homogenous electro-
magnetic enhancement, formation of high intensity hot spots,
and thereby reproducible SERS signals. As a real-life application,
they could detect scrambled prions in biological fluids with a
concentration as low as 1010 M. Another effective method to
fabricate 3D SERS platforms without any post modification is
oblique angle deposition (OAD).96,97 OAD is fundamentally a
vapor deposition technique, which allows the deposition of
nanostructured thin films. Although there is still no consensus
about the exact deposition mechanism in OAD, it is widely
believed that surface diffusion of vaporized materials and self-
shadowing, which restricts the deposition of materials on certain
regions, are responsible for the formation of nanostructured thin
films.98 By manipulation of the deposition parameters (i.e.,
deposition angle (a), and substrate azimuthal rotation (f)), one
can fabricate a variety of unique morphologies including
columnar, helix, and concave using different starting materials.98
Given their simplicity, efficiency and versatility, OAD-based platforms,
therefore, offer unique advantages for high sensitivity SERS
applications. In 2005, Chaney et al. reported, for the first time,
that silver nanorod arrays fabricated by OAD exhibit a good SERS
response with an enhancement factor higher than 108.99 They also
demonstrated that the SERS efficiency of the fabricated platforms
could simply be manipulated by controlling the silver nanorod
lengths. More recently, Wang and co-workers demonstrated an
ultrasensitive SERS platform based on silver nanorod arrays for
the detection of multiple lung cancer related miRNA biomarkers
(Fig. 6).100 In this work, 3D silver nanorod arrays were fabricated
through the OAD approach and modified with hairpin shaped
molecular probes with thiol groups at their 3 0 -ends and Raman
reporters (i.e., ROX, Cy5, and FAM) at their 5 0 -ends. In this way,
they were able to identify target miRNA biomarkers in human
serum at a concentration level lower than 1018 M. In a similar
way, recently, Srivastava et al. prepared nanosculptured thin films
of silver via an OAD technique and investigated their SERS
efficiency in the detection of vitellogenin, a protein biomarker
of endocrine disrupting compounds.101 For the optimized SERS
platforms, the limit of detection for vitellogenin was found to be
5 pg mL1. In addition to sensitivity, reusability, and specificity, the
proposed SERS system provided additional advantages in terms of
miniaturization, small quantity of analyte, and fast response (less
than 3 min) when compared with conventional techniques.

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Fig. 6 (I) Schematic representation of the fabrication and application of the molecular probe modified-silver nanorod array based SERS sensor
platforms, (II) SERS performance of the fabricated platforms for detecting three miRNA mixtures in human serum. SERS spectra of miRNA-21 (A),
miRNA-486 (D) and miRNA-375 (G) for varying concentrations. The semi-log plots of the SERS intensity changes DI1503, DI1368, and DI1321 as a function of
miRNA concentration for miRNA-21 (B), miRNA-486 (E), and miRNA-375 (H), respectively. Specificity assessment of each individual sensor using
complementary and noncomplementary individual miRNA solutions, a mixture of three target miRNA-21/375/486 (mixture 1), and a mixture of all five
miRNAs (mixture 2) for MB-21-ROX (C), MB-486-Cy5 (F), and MB-375-FAM (I), respectively.100 Published by the Royal Society of Chemistry.

In 2014, the Demirel group proposed a new strategy for
sensitive and selective detection of molecules through SERS by
combining 3D gold nanorod arrays with colloidal gold nano-
particles having varying shapes.102 In their work, they first
fabricated 3D gold nanorod arrays via the OAD technique.
Although the fabricated gold nanorod arrays exhibited a good
SERS enhancement ability up to B105, they claimed that
further improvement was still needed especially for the detec-
tion of ultralow concentrations of analytes. To this end, they
first mixed the analyte solution with gold nanoparticles having
different shapes (i.e., spherical, rod, and cage) and dropped
these mixtures onto the fabricated gold nanorod arrays. They
demonstrated that the SERS signals in the presence of colloidal
nanoparticles were dramatically enhanced due to the electro-
magnetic coupling effect of colloidal gold nanoparticles on/in
two or more gold nanorods with a small gap. In this way, they
detected some important chemical and biological warfare
agents, namely dipicolinic acid (DIP), methyl parathion (MP)

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and diethyl phosphoramidate (DP) over a broad concentration
range (5 ppm–10 ppb).
3. Inorganic and organic semiconductor-based SERS
platforms
The scientific discovery and industrial application of (in)organic
semiconductors have exposed new frontiers in the field of opto-
electronics and enabled the realization of everyday electronic
devices such as thin-film transistors (TFTs) and organic light-
emitting diodes (OLEDs).103,104 While inorganic semiconductors
are based on solid-state structures of group III, IV, and V elements
and metal oxides/chalcogenides, organic semiconductors are
p-conjugated carbon-based molecular/polymeric structures that
are bound by relatively weak intermolecular interactions
(e.g., van der Waals, p–p, and C–H  p).105 In the solid-state
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of both types of semiconductor, the formation of band struc-
tures and/or highly delocalized molecular orbitals ensures
efficient charge-transport under the influence of an electric
field as a result of high carrier (i.e., electron or hole) mobility
and low effective carrier mass. Therefore, certain types of these
semiconductors have been widely used in microelectronics
since the 1950s and some have been studied as essential
components of next-generation flexible optoelectronics.106,107
When biological or chemical molecular systems are in the close
vicinity of these semiconductors, the presence of charge-carrier
electrons in the high-energy occupied molecular orbitals (or
valence band edge) and empty orbital states in the low-energy
unoccupied molecular orbitals (or conduction band edge)
allows numerous pathways for charge/energy-transfer processes
in the semiconductor–molecule system under the influence of
an electric field or electromagnetic radiation.108,109 The examples
of these processes have impacted various applications including
chemical/biological sensors, optoelectronics, medicine, and
photocatalysis.110–112
Despite the unique properties of semiconductors such as
structural versatility, facile fabrication, tunable optical and
electronic properties, stable exciton formation, and efficient
charge/energy-transfer processes with molecular structures,
studies on semiconductor-based metal-free SERS platforms
have been very limited lagging behind those of widely studied
metallic (e.g., Au, Ag, and Cu) nanostructures.113 In the beginning,
semiconductors were thought to demonstrate very low enhance-
ment factors due to the lack of plasmon resonances in their
conduction band that can be excited in the UV-vis frequency
range. However, thanks to the advances in the synthesis of
semiconductor nanostructures, they have recently attracted
significant attention in the field of SERS as alternative non-
metallic platforms with EFs of B103–107. The development and
thorough study of semiconductor-based SERS platforms have
been crucial both to further increase the existing enhancement
factors for real-life applications and to fully reveal the mechanism
of the poorly investigated chemical enhancement (CE) since the
dominant enhancement mechanism in semiconductors is not
EM.114 Considering that the electronic band (molecular orbital)
structure of semiconductors could be simply modulated by
varying the solid-state morphology, microstructure, and chemical
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structure (e.g., functionalization, doping, ion incorporation, and
vacancy formation), an in-depth study of the CE mechanism in
the SERS field is plausible with semiconductor-based platforms.
In addition, from a futuristic application perspective, some wide
band gap organic and metal oxide semiconductor films show
optical band gaps of 43 eV and might allow the fabrication of
transparent SERS platforms, which is not practical with metallic
structures.
The CE mechanism is a short-range effect primarily relying
on the amplification of the molecular polarization tensor via
interfacial charge-transfer processes occurring between the
semiconductor surface and chemisorbed analyte molecule. An
efficient charge-transfer process requires good matching of the
orbital wave-functions and energies between the HOMO/LUMO
frontier orbitals of the analyte molecule and the semiconductor
surface’s valence/conduction bands (for inorganic semiconductors)
and HOMO/LUMO frontier orbitals (for organic semiconductors).
The CE mechanism is usually thought to be a ‘‘first-layer-effect’’
requiring a very short semiconductor–molecule distance of
o0.2 nm; therefore, the molecules which are not in direct
contact with the semiconductor surface are not expected to
significantly contribute to this mechanism as they are deposited
on the surface in the upper layers.115,116 As a result of these
aforementioned unique properties, completely different from the
structurally universal metallic substrates, effective with nearly
any molecule, semiconductor-based substrates might pave the
way for molecular structure-selective SERS platforms. The
charge-transfer resonance, under certain circumstances, might
strongly couple with and borrow intensity from nearby allowed
transitions; namely, Mie-type, exciton, and molecular resonances,
depending on the semiconductor–molecule electronic structure
and the excitation laser energy. It’s noteworthy that although
molecular resonance is related to the analyte molecule, exciton
resonance is a unique electronic feature of semiconductors,
which metals do not exhibit, and it involves the creation of an
electron–hole pair in the semiconductor. Considering that some
inorganic semiconductors such as metal oxides are the most
abundant materials in the Earth’s crust and also that organic
semiconductors are synthesized from carbon-based building
blocks obtained from fossil fuel-derived feedstocks, semiconductors
offer the advantage of low material cost as compared to noble
metals. Furthermore, certain semiconductor thin-films and nano-
structures could easily be fabricated on simple substrates (e.g.,
plastic) via routine solution-/vapor-phase procedures performed
at near-ambient conditions in typical fabrication laboratories
without requiring advanced nano-/micro-lithographic processes.
These properties could possibly widen their applicability to
low-cost and flexible SERS platforms in the near future. Greatly
improved biocompatibility of semiconductor-based SERS platforms,
as compared to metallic substrates, offers another key advantage for
biological applications. This section reviews some recent examples
of inorganic and organic-based SERS platforms studied in the past
decade showing appreciable EFs of 100 and higher.
Among all the semiconductors studied to date, metal oxides
are the most extensively studied SERS-active materials. Although
the early proof-of-concept examples of SERS-active metal oxides
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were reported in the 1980s based on crystalline NiO(100 surface)117
and TiO2(001 surface),118 it is the more recent works published
in the past decade that stimulated extensive research yielding
appreciable EFs of 4100–1000 even reaching to remarkable values
of B106–107 via rational nanostructure engineering. One of
the early examples of metal oxide semiconductor-based SERS
platforms with noticeable EFs came from the study led by
Lombardi and co-workers,119 in which they obtained clear
evidence of surface-enhanced Raman signals from 4-mercapto-
pyridine (4-MPy) molecules adsorbed on spherical ZnO nano-
crystals with an average particle size of B20 nm. A respectable
enhancement factor of 103 was achieved as a result of the
efficient chemical enhancement mechanism, which is attri-
buted to the charge transfer taking place between the ZnO
valence band edge and 4-MPy’s unoccupied p*-orbitals. This
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result demonstrated a significant improvement over the earlier
report on ZnO colloid-based SERS substrates showing an EF
of only B50 for a cyanine dye.120 In a related study, Lombardi
and Zhao studied the Raman intensity of two different mole-
cules (4-mercaptopyridine and 4-mercaptobenzoic acid)
adsorbed on the surface of ZnO nanocrystals as a function of
semiconductor particle size (18–31 nm). They showed a large
increase in Raman intensity at the particle size of B28 nm,
which stems from the formation of a highly efficient charge-
transfer complex specifically at this size between a surface-
bound exciton and the adsorbed molecule.121 In further studies
by the same researchers, ZnS nanocrystals (B3 nm particle
size)122 and CdTe quantum dots (B3 nm particle size)123 were
used as Raman scattering platforms and EFs of 103–104 were
measured with the 4-MPy reporter molecule. Since plasmon
resonances were ruled out for these semiconductor systems, a
charge-transfer mechanism was suggested to be responsible for
the observed enhancements. These results were crucial to prove
that non-metallic SERS platforms could be extended to nano-
structured metal chalcogenides. Later, ZnO-based semiconductor
SERS platforms were extended to various nanostructures
including nanorods, nanowires, and nanocones.124,125 In one
of these studies, Shi and coworkers investigated the effect of
the relative energies of the probe molecule’s HOMO/LUMO and
the ZnO-nanorod (NR)’s valence-conduction band edges on the
SERS responses.124 They used two probe molecules, 4-mercapto-
pyridine (4-MPy) and 4-aminothiophenol (PATP), with similar
p-electron densities and –SH groups to strongly bind to the
semiconductor surface, but with different HOMO and LUMO
energetics. Under the same laser excitation wavelength of
532 nm (2.3 eV), while 4-MPy molecules on ZnO-NR showed
strong Raman signals, PATP molecules on the same ZnO-NR
showed almost no Raman signals. The substantial difference
between the two molecules is attributed to the thermodynamic
feasibility of the corresponding charge-transfer processes
between the semiconductor VB-edge (CB-edge) and the mole-
cular LUMO (HOMO). Similarly, when 4-MPy molecules on
ZnO-NR were excited with lower laser frequencies, no Raman
signals were observed below 2 eV of pumping energies. This
threshold energy roughly corresponds to the energy difference
between the ZnO-NR VB edge (7.7 eV) and the 4-MPy LUMO
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Journal of Materials Chemistry C
(5.1 eV), below which the charge-transfer process is not
thermodynamically feasible. These results clearly revealed that
the presence of a thermodynamically allowed charge-transfer
process is crucial to magnify the molecular polarizability
tensor and to realize high SERS effects. Here, the authors also
demonstrated that the ZnO-NR surface could enable molecular
detection in pharmaceutical analysis by proving efficient
chemisorption and SERS analysis of acetaminophen and a
ruthenium-dye with functional groups of –COOH and –OH,
respectively.
In a later study by Yoon and co-workers,125 good Raman
enhancements of 103 were observed for 4-MPy adsorbed on ZnO
nanowires and nanocones, which was found to be strongly
dependent on the geometry of the ZnO nanostructures. The
results could be explained by using finite-difference time-
domain (FDTD) calculations, which indicated substantial
differences in the cavity-like structural resonance of the electric
field intensity on the surface for different geometries. Based on
the simulations, the strongest field concentration was calcu-
lated for excitation energies of 400–500 nm, which is in agree-
ment with the experimental results. Finally, unlike previous
works on ZnO nanoparticles, the authors observed Raman
signals even with the excitation laser energy of 1.58 eV, at
which charge-transfer processes are not thermodynamically
likely, which further confirmed the existence of electromagnetic
contribution to SERS. In a very recent study, Guo et al. developed
hollow ZnO nanocages as an efficient SERS platform.126 The
rationally designed hollow amorphous ZnO affords an ideal
optical resonant cavity for light-harvesting and also provides a
large surface area for analyte molecule adsorption, which leads to
an impressive enhancement factor of up to 6.6  105. In their
study, the group prepared comparative amorphous (a-ZnO NCs)
and crystalline ZnO nanocages (c-ZnO NCs) with dimensions
of around 600 nm by using a highly uniform Cu2O nanocube
template (Fig. 7). Three different mercapto molecules (4-mercapto-
benzoic acid, 4-mercaptopyridine, and 4-aminothiophenol) were
used as probe molecules; and, for all molecules, a-ZnO NC surface
showed much higher Raman peak enhancements as compared to
those of c-ZnO NC. Since similar specific surface areas (SSAs) were
measured for a-ZnO and c-ZnO NCs, the high EF for a-ZnO NC is
attributed to its metastable electronic state which endows the
surface electrons with a weaker constraint resulting in a more
efficient interfacial charger-transfer process. This is further con-
firmed by first principles density functional theory simulation,
and supported by X-ray absorption near-edge structure (XANES)
characterization indicating the formation of strong molecule–
semiconductor bonds (sigma- and p-bonding in the Zn–S bonds).
These results are remarkable since, for the first time, such a
high EF was obtained from an amorphous (nanostructured)
semiconductor-based SERS platform, which could open a new
frontier in the field.
Following the advancements in the field of semiconductor
nanostructure synthesis in the past few decades, the surface
states of semiconductor nanostructures, and thus their inter-
action with the molecular structures in close proximity, could
be finely tuned via defect engineering. This has impacted the
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Fig. 7 Schematic illustration of the fabrication of a- and c-ZnO NCs.
Representative SEM (a and b) and TEM (c and d) images of a- and c-ZnO
NCs (the insets indicate the SAED patterns of a- and c-ZnO NCs),
respectively. The high resolution TEM micrographs (e and f) obtained from
the red boxes in image (c) and (d), respectively. Reproduced with permission
from ref. 126. Copyright (2017) John Wiley & Sons, Inc.
recent progress in the field of semiconductor SERS platforms
by greatly improving the enhancement factors up to 106–107,
Fig. 8 (a) UV-vis spectra for R6G on W18O49 compared with pristine W18O49 and R6G dye. (b) Energy-level diagram of R6G on oxygen-deficient W18O49
measured in a vacuum. Reproduced from ref. 127.
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which is comparable to those reported for noble metals. Among
various methods to tune the surface states of semiconducting
materials, adjusting the oxygen deficiency represents one of the
promising approaches reported by Zhao and co-workers.127
In this study, oxygen vacancy-containing tungsten-oxide material,
W18O49, was synthesized from WCl6 using a conventional hydro-
thermal approach. This sample comprised entangled thin nano-
wires (several micrometers length and 10–20 nm width) forming
a spherical sea urchin-like morphology. As a comparative SERS-
platform, a defect-free WO3 substrate was also prepared from
W18O49 after thermal annealing in air. Using the R6G Raman
probe molecule, while no clear Raman signals were observed on
WO3, substantial peaks were evident on the W18O49 sample
corresponding to four characteristic bands of the probe molecule.
An enhancement factor as high as 1.9  105 was measured on
pristine W18O49, and the detection limit concentration was as low
as 107 M. To validate the key role of oxygen vacancies in SERS,
additional surface vacancies were intentionally created by
annealing the pristine W18O49 material in an Ar or H2 atmo-
sphere, which was found to yield further Raman intensity
enhancement (2–3) reaching an EF value of 3.4  105.
The observed high EFs were attributed to thermodynamically
feasible charge-transfer processes (chemical enhancement
mechanism) in the W18O49–R6G system employing molecular
resonance (mmol), exciton resonance of defect states (mex),
photon-induced charge-transfer resonance (mPICT), and ground-
state charge-transfer resonance (mGSCT) (Fig. 8b). The efficient
charge-transfer in the W18O49–R6G system was clearly evident in
the absorption spectrum of R6G molecules deposited on W18O49
with the occurrence of a new band at B580 nm (Fig. 8a).
Following the same oxygen-vacancy formation approach, Li and
co-workers recently transformed a poorly SERS active stoichiometric
a-MoO3 substrate into a SERS active a-MoO3x substrate with a
maximum EF of 1.8  107 and a detection limit of 108 M for the
R6G probe molecule.128 This is, to the best of our knowledge, the
highest EF reported to date based on a semiconductor platform and
comparable to those reported for noble metals. In this study,
a-MoO3x was prepared as nanobelts via a hydrothermal method,
and the SERS spectra of 4-MBA, MB, and R6G probe molecules were
measured as a function of vacancy concentration. A model named
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the ‘‘effective electric current model’’ was used by the authors to
describe the photo-induced charge-transfer processes in this
semiconductor–molecule system, which was found to agree very
well with the experimental results. Based on this model, the
authors also proposed that oxygen vacancy defects might induce
significant SERS-activity for CrO3 and Ta2O5 materials. Recently,
Guo et al. used a similar defect-engineering strategy and
developed a 3D cube-like superstructure based on Cu2O meso-
porous spheres (300 nm) using a recrystallization-induced
self-assembly method.129 In this material, during the formation
of the superstructure, a large number of defects were generated
resulting in the formation of copper vacancies through the lattice
fusion of neighboring Cu2O mesoporous spheres. As a result,
surface vacancy defect states were formed about 0.5–0.9 eV below
the conduction band edge of Cu2O and facilitated photo-induced
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electron transfers in the Cu2O–R6G system yielding an enhanced
molecular polarizability tensor and Raman scattering intensity
(EF = 8  105, nM level detection sensitivity). For this material,
when the level of vacancy defects was increased via thermal
annealing, higher Raman signals were observed. In addition,
because of the negatively-charged nature of the copper vacancies,
an electrostatic adsorption effect was evident in the form of charge-
selective SERS performance. Higher EFs (B10) were measured for
positively charged probe molecules (R6G and CV) when compared
with negatively charged probe molecules (MB and MO).
After discovering that oxygen vacancies could increase the
enhancement factors for metal oxide semiconductors that were
previously considered to be not SERS active, Zhao et al. put
another interesting idea into practice.130 They proposed
whether oxygen incorporation, as the inverse process of vacancy
formation, into transition metal chalcogenides could alter
the materials’ electronic/structural properties and facilitate
the chemical enhancement mechanism. In this study, pristine
MoS2, oxygen-substituted MoS2xOx, partially oxidized MoSxOy,
and completely oxidized MoO3 were developed by hydrothermal
synthesis and thermal annealing methods (Fig. 9). In these
structures, oxygen incorporation has two different impacts:
substitution of oxygen for sulfur in the lattice and partial
oxidation of molybdenum atoms along edge planes or at defect
Fig. 9 Low-temperature hydrothermal synthesis of MoS2xOx using (NH4)6Mo7O244H2O and thiourea (a and b). Thermal annealing of MoS2xOx at
300 1C for 30 min in air leading to the formation of partially oxidized MoSxOy without changing its crystal structure (c). Thermal annealing of MoS2xOx at
400 1C for 30 min in air yielding completely oxidized MoO3 having a different crystal structure to MoSxOy (d). Reproduced from ref. 130.
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sites. The SERS behaviors of these materials were examined by
using the R6G probe molecule and were found to be completely
different from each other. While pristine MoS2 and completely
oxidized MoO3 gave almost no Raman signals, both oxygen-
substituted and partially oxidized MoS2 substrates showed
quite obvious Raman signals of R6G. The EFs were calculated
to be 1.1  104 and 1.4  105, respectively, and the detection
limit was found to be 107 M. This approach was demonstrated
to be also highly effective in other poorly SERS-active transition
metal chalcogenides MoSe2 and WS2, both of which reached
EFs of around 105 after being thermally annealed at 350–400 1C
in air. The observed high SERS enhancements for these
partially oxidized materials stems from thermodynamically feasible
charge-transfer resonances in the semiconductor–molecule system
and coupling of this charge-transfer resonance with nearby
molecular/exciton resonances. Similar to the mechanism of
oxygen vacancy formation, the incorporation of oxygen intro-
duces additional energy levels into the semiconductor electronic
structure, which facilitates the charge-transfer process in the
semiconductor–molecule system and improves the semiconductor
exciton resonance.
Thanks to the varied oxidation states employed by transition
metals, some nanostructures of lower oxidation-state metal
oxides could show electrical conductivity while their higher
oxidation-state metal oxide equivalents are only semiconducting.
MoO2 is a typical example of this, which was recently reported
by Xi and colleagues with low electrical resistivity (6.12 
103 ohm cm at 300 K), similar to metals, along with high
chemical stability and melting point.131 In contrast to its
semiconducting analogue MoO3, MoO2 presents a metallic
character with a large number of surface plasmon resonance
(SPR)-active free electrons. Although the highest occupied
states of semiconducting MoO3 are made of O2p orbitals, which
tend to localize electrons around the oxygen atoms, occupied
states near the Fermi level of MoO2 are composed of Mo3d
orbitals giving it metallic character and high free electron
density. MoO2 was synthesized by a simple surfactant-free
hydrothermal method under relatively mild experimental
conditions with no inert gas protection, and it is composed of
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Journal of Materials Chemistry C
dumbbell-like nanostructures having many ultrathin nanosheets
(2.5 nm in thickness) with sharp corners, edges, and nanoscaled
gaps. This particular morphology was thought to be advanta-
geous to generate a high density of hot-spots. The optical
absorption spectrum of MoO2 nanodumbbells showed a strong
and well-defined peak centered at 563 nm, which was attrib-
uted to the SPR effect as a result of the presence of d-orbit free
electrons. Remarkably, the observed SPR peak was found to
be unchanged even after 300 1C heating, acid/alkali exposure,
or photochemical stability tests. The SERS measurements
performed by using the R6G probe molecule indicated EFs as
high as 3.75  106 and analyte detection limits as low as
107 M. When MoO3 nanodumbbells were used as the com-
parative SERS substrate, no Raman signals were observed for
R6G. In the same study, the authors heated the conducting
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MoO2 material in air at higher temperatures (350–450 1C)
yielding an increase in the metal oxidation state and reduction
of free electron density, which resulted in greatly decreased
SERS performance. In addition to the electromagnetic
enhancement, the effect of charge-transfer was also found to
play an important role in SERS for the MoO2 material since new
semiconductor-to-molecule charge transfer bands were observed
in the absorption spectrum of MoO2–R6G. Finally, the new plat-
form was shown to be very effective in detecting trace levels of
various high risk chemical species such as bisphenol A (BPA) and
2,4-dichlorophenol (DCP).
Several novel strategies regarding the enhancement of
electromagnetic wave-molecule interactions within inorganic
semiconductor micro-/nanostructures have been explored in
the past decade to improve the SERS performance of semi-
conductors. Among these, inspired by the original studies
performed on dielectric microspheres for optical sensing,
Alessandri demonstrated significant Raman scattering enhance-
ments for MB molecules adsorbed on the colloidal assembly of
SiO2–TiO2 core–shell microsphere resonators.132 The formation of
very effective total internal reflection in this structure yields
evanescent electromagnetic fields to generate local surface hot
spots (whispering-gallery-mode resonances), which, based on a
theoretical study by Ausman and Schatz,133 could overlap with the
Raman scattered radiation to result in high EFs typically observed
in noble metals. The core–shell microspheres were synthesized by
conformably coating silica cores with an amorphous titania thin
shell via the atomic layer deposition (ALD) technique, which was
followed by annealing at 700 1C to promote crystalline anatase
formation. The SERS study was performed against planar TiO2
films grown on the same substrate via the ALD process. The
enhancement was ascribed to the synergistic interplay of TiO2’s
high refractive index (2.5) and multiple light scattering, which
increase the optical path for the photons resulting in the enhance-
ment in Raman scattering. Moreover, the author showed that this
SERS substrate is recyclable thanks to the photocatalytic activity of
anatase TiO2 under UV irradiation. In a later study by the same
author and co-workers, SiO2/TiO2 core/shell beads were designed
and studied for Raman detection of environmental CO2 molecules
down to the 396 ppm level.134 Similar approaches were also
employed with TiO2 photonic microarrays135 and Si nanowire
5328 | J. Mater. Chem. C, 2018, 6, 5314--5335
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arrays136 to demonstrate highly effective semiconductor-based
SERS platforms for the detection of methylene blue molecules
down to 107 M concentration. In both cases, light-matter
interaction is enhanced via similar repeated/multiple light scat-
tering and trapping processes within micro-/nanostructured
morphologies.
The search for alternative non-metallic SERS platforms has
recently turned to a completely new direction by focusing on
carbon-based architectures employing p-conjugated delocalized
electronic systems. When compared with saturated organic
systems having only low-energy sigma-electrons, the presence
of relatively high-energy/mobile p-electrons and low-energy
unoccupied p* molecular orbitals that are effectively delocalized
over a large number of covalent bonds enables charge-transport
and facile interaction of these organic systems with light/electric
fields. As a result, numerous organic p-conjugated systems with
diverse molecular structures have been designed and synthesized
to date, showing various optical and electrical properties. Most
importantly, p-conjugated (macro)molecular systems have also
demonstrated very promising energy-/charge-transfer characteris-
tics with various organic molecules. Nevertheless, when compared
with inorganic and metallic SERS platforms, reports on Raman
enhancement on purely organic substrates have been very limited
although they offer advantageous properties such as biocompat-
ibility, low material cost, processibility, structural versatility,
and efficient charge-transfer. In particular, quantitative analysis
might be possible on highly homogeneous organic surfaces
(e.g., graphene or smooth molecular films) since they could
provide a uniform environment for well-controlled molecular
adsorption/chemisorption on the surface.137 To this end,
pristine organic substrates based on semiconducting small
molecules and single-to-few graphene layers have received
recent attention as efficient Raman enhancement surfaces as
a result of their strong charge-transfer properties with the
adsorbed/chemisorbed probe molecules.138 Since plasmon
resonance for graphene is in the range of terahertz and small
molecular thin-films do not exhibit plasmonic properties, the
CE mechanism is considered to be the major contributor to
Raman enhancement for these platforms.
Graphene is a single sheet of graphite, in which a monolayer
of sp2-hydridized carbon atoms is packed into a two-dimensional
(2-D) honeycomb crystal structure. It can be obtained by
mechanical exfoliation from highly ordered pyrolytic graphite
or Kish graphite, which are abundant on the Earth’s surface.
Since its discovery in 2004,139 graphene has shown excellent
mechanical, electrical, and optical properties, and it has been
extensively studied in various applications ranging from transis-
tors to sensors. The first report on the Raman enhancement
behavior of graphene was published in 2010 by Liu, Zhang, and
co-workers.116 In this study, the authors deposited some common
probe molecules (phthalocyanine (Pc), rhodamine 6G (R6G),
protopphyrin IX (PPP), and crystal violet (CV)) on monolayer
and few-layer graphene (on Si–SiO2 (300 nm) substrates) by using
vacuum evaporation and solution-soaking techniques. Strong
Raman signal intensities were observed on monolayer graphene,
as compared to the Si–SiO2 (300 nm) reference substrate resulting
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Published on 23 April 2018. Downloaded on 12/11/2018 8:46:16 AM.

Fig. 10 (a) Schematic illustration of SERS measurements of analyte molecules on graphene and a SiO2/Si substrate. (b–d) The SERS spectra of Pc
(2 Å) deposited on graphene (red line) and on the SiO2/Si substrate (blue line) at 632.8 nm (b), 514.5 nm (c), and 457.9 nm (d) laser excitation
wavelengths, respectively. (e–g) Analogue to (b–d), but depositing thinner Pc (B1 Å). Except for the peak marked by the star (*) (the 960 cm1 peak from
Si, and the 1586 cm1 peak from graphene), all the peaks are from Pc. Reproduced with permission from ref. 116. Copyright (2010) American Chemical
Society.

in EFs of 2–17 and detection limits of 108–1010 M (Fig. 10).
Using pure graphene as a SERS platform without additional
plasmonic materials is called graphene-enhanced Raman
scattering (GERS). When Raman measurements were performed
on surfaces with different numbers of graphene layers, the
intensities were found to decrease going from monolayer to
multilayers. On the graphite, the signals were either very weak or
invisible. The authors ascribed this trend to the differences in
the electronic structures (i.e., Fermi levels) of graphene with
various layers, which lead to different energy band matching
(doping effect) with probe molecules.140 Considering that EM is
unlikely for graphene at 632.8 nm, 514.5 nm, and 457.9 nm laser
excitation wavelengths, the observed SERS enhancements were
attributed to pure CE mechanism as a result of the structurally/
energetically suitable graphene surface enabling efficient charge-
transfer processes. In addition, the Raman enhancement was
found to be dependent on the vibrational symmetry of the
molecules, which further supports the CE mechanism. This
discovery was actually the result of follow-up SERS experiments
performed on graphene after the same research group’s earlier
results,141 in which they measured the resonance Raman spectra
of R6G and PPP with greatly suppressed (B103 times) fluores-
cence (FL) background when adsorbed on graphene.
A later study by Zhang et al. on Langmuir–Blodgett (LB)
films of protoporphyrin IX (PPP) (1–4 layers) in contact with
graphene revealed that GERS is strongly dependent on the
distance between graphene and the probe molecule.142 The
first monolayer LB film of PPP was found to show the largest
contribution to the Raman enhancement as compared to the
subsequent layers, and the functional groups in direct contact
with graphene showed much higher Raman signals than other
groups in the probe molecule. Furthermore, in a separate study,
GERS was found to be very sensitive to the molecular orienta-
tion by giving larger Raman responses for face-on (lying-down)
oriented molecules as compared to those with edge-on
(upstanding) orientation.143 Annealing allowed a planar probe
molecule, copper phthalocyanine (CuPc), in a LB film to change
orientation from edge-on to face-on, which induces enhanced
p–p interactions between the CuPc molecules and graphene
resulting in a larger interfacial dipole (polarizability) and
more plausible charge-transfer. In order to increase the EFs
of graphene platforms, p-doped graphene structures with
oxygen-containing functional groups were prepared by Nam
et al. by using UV/ozone-based oxidation methods.144 As a result
of structural disorder and p-doping effects on the surface, the EFs
were found to increase to B104 when R6G probe molecules were
used. In addition, the degree of SERS enhancement could be
controlled by tuning the UV/ozone exposure time. In a similar
study by Luo and Wang,145 it was found that mildly reduced
graphene oxide nanosheets could exhibit an EF of B103, which is

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Journal of Materials Chemistry C Review

higher (10) than that with the mechanically exfoliated graphene.
The presence of highly electronegative oxygen species was claimed
to introduce a strong local electric field on the adsorbed mole-
cules to yield large Raman enhancements. A strong molecular
selectivity was discovered for the GERS effect in a study led by Ling
and Dresselhaus, which indicated that EFs might change up to
2 orders of magnitude depending on the HOMO–LUMO energy
levels (with respect to graphene’s Fermi level) and structural
symmetry of the probe molecules.146 In a very recent work, a
quasi-equilibrium plasma-enhanced chemical vapor deposition
method was developed to grow highly crystalline, atomically clean
graphene quantum dots (GQDs) directly on Si–SiO2 with sizes
down to 2 nm.147 These GQD-based substrates were directly used
as a SERS platform without requiring any post-growth transfer
process, and they showed EFs of up to 2.37  103 (with R6G),
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group to question whether small molecules and their micro-/
nano-structured thin-films with well-controlled p-architectures
could exhibit similar Raman enhancement properties. The
design and application of functional organic films based
on p-conjugated small molecules has been a widely studied
research field for optoelectronic devices in the past several
decades, particularly including thin-film transistors, photo-
voltaics, and light-emitting diodes. However, until our very
recent study, organic molecular films have never been used
as SERS platforms despite their very attractive properties such
as structural versatility, facile and highly controllable synthesis/
film-fabrication, and fine-tuning of optoelectronic properties.148
Specifically, the fact that molecular structures of small molecules,
and hence their electronic structures, are tunable could open the
possibility of designing target-specific SERS platforms, so-called

much higher than those on conventional graphene sheets, and
detection sensitivity down to 109 M (with R6G). With the
assistance of DFT calculations, the impressive Raman enhance-
ment performance of this new substrate was attributed to
its unique structural and electronic properties, which leads to
enhanced light–matter interaction, a large amount of accessible
edges for absorption, and efficient charge-transfer processes
with the probe molecules. Importantly, the efficiency of charge-
transfer, hence the degree of Raman enhancement, was found to
be strongly dependent on the energy alignment between the
frontier orbitals of target molecules and GQDs, which is governed
by the size of the quantum dots.
The great success achieved with graphene-based substrates
in realizing SERS-active platforms has prompted our research
molecular sensitive SERS. Note that this has not been possible
with metallic, inorganic, and even graphene-based platforms
since the exploratory synthetic modifications are limited on
these structures. In our recent study, superhydrophobic, highly
crystalline, 3D ivy-like nanostructured organic films (B20 mm)
were grown on 5 cm-diameter Si(100) substrates by using a facile
physical vapor deposition (PVD) method (Fig. 11).148 The molecule
used in this study was the perfluorohexyl-substituted quater-
thiophene semiconductor, DFH-4T, in which the p-electronic
structure provides efficient electron transport and perfluoroalkyl
chains provide excellent volatility and superhydrophobicity.
In order to realize this unique morphology via vertical crystal
growth, an ultrafast deposition rate of 440 nm s1 and a short
source-substrate distance of B7 cm were used. When methylene

Fig. 11 (a) Optical image of a vapour-deposited DFH-4T film (5 cm in diameter) with the chemical structure shown in the inset. (b–d) The representative
top-view (b and c) and cross-sectional (d) SEM images of fabricated DFH-4T films. (e) The XRD pattern of a nanostructured DFH-4T film and the view of
the molecular packing along the [3 1 1% ] crystal growth direction showing the dominant CH-interactions. (f) Optical image of a water droplet on a
nanostructured DFH-4T film used for contact-angle measurements. Reproduced with permission from ref. 148. Copyright (2017) Nature Publishing
Group.

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Table 1 The EF and LOD values of SERS platforms discussed in this review

SERS platform Probe molecule EFa LODb Ref.

Metal nanoparticle-based platforms
Dye-incorporated Au nanorod IR-792 perchlorate dye (IR-792) NA 4  1016 M (IR-792) 27
Au nanotriangle Benzothiol (BT) 1.2  105 108 M (BT) 29
Ag nanotriangle 4-Mercaptobenzoic acid (4-MBA) 3.4  105 NA 30
Concave Au nanocube assembly 4-Methylebenzenethiol (4-MBT) 106 2  106 M (cytochrome c) 40
Iodide-modified Ag nanoparticle NA NA 3 mg mL1 (lysozyme) 44
Aptamer driven Au nanoflower–Ag NP NA NA 8.6  1012 M 47
assembly (microcystin-LR)
Ag+ ions-mediated AuNP aggregates 4-Aminobenzenethiol (4-ABT) 2.05  105 30  1015 M (DNA) 49
Shell-isolated nanoparticle (Au@SiO2) Three-dimensional 4  108 NA 53
finite-difference time-domain
calculation
DNA origami based Au–Ag core–shell Cyanine dye (Cy3) 1010 Single molecule 57
nanoparticle level detection (Cy3)
Au@Ag core–shell nanorods in a micro- NA NA 1  106 M (thiocyanate) 60
fluidic chip
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Three-dimensional plasmonic platforms

Au NP decorated 3D nanoporous film BT 105 NA 63
Ag nanodisk pattern NA NA 108 M (crystal violet) 69
109 M (mitoxantrone)
Silver decorated nanostructured- Rhodamine 6G (R6G) 4.9  106 107 M (R6G) 70
polycarbonate film
9 9
Ag NP decorated electrospun PVA 4-MBA 10 10 M (4-MBA) 71
nanofibers
Au NP loaded filter paper NA NA 109 M (4-nitrothiophenol) 72
Au deposited cellulose fiber matrix NA NA 25  106 M (uric acid) 75
Ag decorated nanostructured PPX film 4-Flurobenzentiol 106 1010 M (RSV gene) 76
Ag deposited bowl-shaped PDMS film R6G 1.4  106 0.05 mg mL1 77 and 78
(albumin, cytochrome c)
Ag NP coated silicon nanowire array NA NA 4  106 M 87
(calcium dipicolinate)
In situ AgNP deposited silicon nanowire Methylene blue (MB) 106 109 M (MB) 88
array
Graphene-encapsulated Au NP decorated R6G 107 NA 89
silicon nanowire
7 2
Ag NP decorated silicon wafer 4-Mercaptophenylboronic acid 1.3  10 10 cells per mL 90
(E. coli and S. aureus)
Gold nanorods 3D-supercrystal platform — NA 1010 M (scrambled prion) 95
Ag nanorod array trans-1,2-Bis(4-pyridyl)ethane 4108 B1018 M (miRNA) 96 and 100
Au nanorod array MB 4106 10 ppb (dipicolonic acid) 102

Inorganic and organic semiconductor-based platforms

Graphene Phthalocyanine (Pc), rhodamine 2–17 8  1010 M (R6G) 116
6G (R6G), protopphyrin IX (PPP), 2  108 M (PPP)
and crystal violet (CV)
TiO2 Pyridine 103–104 NA 118
ZnO nanocrystals 4-Mercaptopyridine (4-MPy) 103 103 M 119
ZnO colloids Cyanine dye (D266) B50 105 M 120
ZnS nanocrystals 4-MPy 103 106 M 122
CdTe quantum dots 4-MPy 104 NA 123
ZnO nanorod arrays (ZnONRs) 4-MPY, acetaminophen and NA 104 M (4-MPY and 124
(Bu4N)2[Ru(dcbpyH)2-(NCS)2] acetaminophen),
(N719) 107 M (N719)
ZnO nanowires and nanocones 4-MPy 103 0.2 M 125
Amorphous ZnO nanocages (a-ZnO NCs) 4-MPy 6.62  105 NA 126
W18O49 nanowire R6G 3.4  105 107 M (R6G) 127
a-MoO3x nanobelts 4-MBA, R6G and MB 1.8  107 108 M (R6G) 128
107 M (MB)
Cu2O mesoporous spheres R6G 8  105 109 M 129
MoS2xOx and MoSxOy R6G 1.1  104 107 M 130
(MoS2xOx)
1.4  105
(MoSxOy)
MoO2 R6G 3.75  106 107 M (R6G) 131
SiO2/TiO2 core/shell beads (T-rex) Environmental CO2 NA B400 ppm 134
(environmental CO2)
TiO2 photonic microarrays MB 2  104 6  106 M 135
Si nanowire arrays MB NA 107 M (MB) 136

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Table 1 (continued)
SERS platform Probe molecule
Graphene R6G
Mildly reduced graphene oxide (MR-GO) Rhodamine B (RhB)
nanosheets
Graphene quantum dots (GQDs) R6G
Perfluorohexyl-substituted MB
quaterthiophene (DFH-4T)
Au@DFH-4T MB
a b
EF = enhancement factor. LOD = limit of detection.
blue was used as a probe molecule, DFH-4T films without any
additional plasmonic layer exhibited unprecedented Raman
signal enhancements up to 3.4  103, which was the first time
that a small molecular thin-film enhances Raman signals in the
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SERS field. Considering that DFH-4T film has an extremely low
intrinsic charge-carrier density (o1013 cm3), chemical enhance-
ment was considered to be the dominant mechanism relying on
resonance charge transfer processes between the DFH-4T surface
and the analyte molecules as supported by quantum mechanical
calculations.149 In addition, comparative experiments on thin-
films with either a fluorocarbon-free DH-4T semiconductor
or relatively smoother morphologies indicated that both the
molecular structure and film morphology played significant roles
in the performance of this organic SERS-platform. Finally, we
showed that nanostructured DFH-4T films were excellent low-
surface energy templates for additional plasmonic metal deposi-
tion and that closely packed gold nanoparticulates (9–16 nm
in size) could be deposited via PVD. This organic–metal hybrid
platform enabled Raman signal enhancements of up to 1010 and
sub-zeptomole (o1021 mole) analyte detection. The realization
of organic semiconductor-based SERS platforms might open the
door to fabricating large-area platforms by using low-cost and
facile techniques such as physical vapor deposition and solution-
processing with no requirement of advanced lithographic
techniques. Despite the very promising results obtained here,
further research is certainly needed to develop a library of
compounds as new SERS platforms and to explore structure–
property–SERS response relationships in a greater detail. This will
not only boost enhancement factors but also reveal the structural
requirements of organic systems to enable much higher SERS
activity.
Conclusions
The design and fabrication of SERS-active platforms with varied
chemical structures and properties have made remarkable
progress since its discovery in the 1970s, and today very high
Raman signal enhancements and single-to-few molecule
level detection limits are achieved. Fundamental and applied
research in SERS combining theory, materials synthesis, and
nano-/microfabrication tools have played a central role in the
realization of these platforms, which has been directly inspired
by the advancements in these fields in the past decades. The
field of SERS bridges research on Raman spectroscopy and
5332 | J. Mater. Chem. C, 2018, 6, 5314--5335
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Review
EFa LODb Ref.
4
10 NA 144
103 5  108 M (RhB) 145
2.37  103 1  109 M (R6G) 147
3.4  103 1  105 M 148
1010 o1021 mole 148
materials science, and raises many interesting opportunities
in not only the fabrication of novel materials but also their
applications in life sciences. As presented in detail in this
review, the recent focus on SERS-active materials has shifted
from conventional plasmonic surfaces to alternative three-
dimensional structures and nano-/microstructured semi-
conductors with fine-tuned electronic properties. The EF and
LOD values of SERS platforms mentioned in this review are also
summarized in Table 1 as a simple guide for the readers.
Among the SERS platforms, inorganic and organic semi-
conductors have gained extensive attention in the past few
years showing continuously improving SERS performances
and bringing in new promises such as molecular sensitivity
(i.e., on small molecular film surface) and quantitative detection
(i.e., on smooth two-dimensional graphene surface). Although
much of the theoretical enhancement mechanisms for metallic
and inorganic materials have been established, at least in
principle to explain the observed SERS results, a strong under-
standing of the enhancement mechanism is still required
in carbon-based p-conjugated SERS platforms. In our opinion,
further development of high-performance, unconventional SERS
platforms is essential, not only to open up new opportunities
for real-life applications in the fields of medical diagnostics,
environmental protection, food safety, and even homeland
security, but also to develop a strong understanding of material
structure–property–SERS performance relationships.
Conflicts of interest
There are no conflicts to declare.
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