Surface-Enhanced Raman
Spectroscopy (SERS):
General Introduction
Song-Yuan Ding, Xue-Min Zhang, Bin Ren, and
Zhong-Qun Tian
Xiamen University, Xiamen, China
1 Introduction
2 Surface-Enhanced Raman Scattering
2.1 Principles of Surface-enhanced Raman
Scattering
2.2 Methods for Preparing Surface-enhanced Raman
Scattering Substrates
2.3 Measurement Procedures of Surface-enhanced
Raman Scattering
2.4 Utilization of the Strength and Offset of the
Weakness of Surface-enhanced Raman
Scattering
3 Tip-Enhanced Raman Spectroscopy
3.1 Principles of Tip-enhanced Raman
Spectroscopy
3.2 Preparation of the Tip-enhanced Raman
Spectroscopy Tip
3.3 Tip-enhanced Raman Spectroscopy
Experiments
3.4 Applications of Tip-enhanced Raman
Spectroscopy
4 Shell-Isolated Nanoparticle-Enhanced
Raman Spectroscopy
4.1 Principles of Shell-isolated Nanoparticle-
enhanced Raman Spectroscopy
4.2 The Generality of Shell-isolated
Nanoparticle-enhanced Raman
Spectroscopy
4.3 Reliability of Shell-isolated
Nanoparticle-enhanced Raman
Spectroscopy
4.4 Flexibility of Shell-isolated
Nanoparticle-enhanced Raman
Spectroscopy
5 Outlook and Summary
Acknowledgments
Abbreviations and Acronyms
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
Related Articles 25
References 25
Surface-enhanced Raman scattering (SERS) was discov-
ered in the mid-1970s, by which the intrinsically low
detection sensitivity of Raman spectroscopy is no longer a
fatal disadvantage for this analytical tool. As a general
introduction of SERS, the almost 40-year history of
SERS is first overviewed, showing that SERS has gone
1 through a tortuous pathway to develop into a powerful
6 diagnostic technique. We then describe the principle of
SERS and enhancement mechanisms, illustrating that
SERS is mainly surface plasmon resonance (SPR)-
6
and nanostructure-enhancement phenomenon. The SERS
measurement procedures, in particular the preparation
12 of various SERS active substrates, are discussed. On the
basis of four important criteria in analytical science, i.e.
14 detection sensitivity, (energetic, spatial, and temporal) reso-
lution, generality, and reliability, we highlight two different
approaches to utilize the strength and offset the weak-
17 ness of SERS. With the enormously high sensitivity and
19 spectral resolution, SERS has been applied successfully to
surface analysis and trace analysis by gaining meaningful
19 information from an extremely small quantity of species
even down to single molecules. To significantly improve
20 the surface generality and spatial resolution, tip-enhanced
Raman spectroscopy (TERS) was invented in 2000. To
greatly improve the material generality and measurement
20
reliability, shell-isolated nanoparticle-enhanced Raman
spectroscopy (SHINERS) was introduced in 2010. Finally,
21
prospective developments of SERS in substrates, methods,
and theory are briefly discussed.
21
21 1 INTRODUCTION
The continuous development of analytical chemistry
22 relies on the emergences of new methods and further
improvement of well-established techniques, meeting the
demands of fundamental research studies and practical
22 applications. As one of the important constituents of
analytical chemistry, analysis of ultratrace molecules or
species in complex systems has received an increasing
23 attention. It includes in situ investigation of molec-
24 ular adsorption and reactions in interfaces on the
(sub)monolayer level, in vivo investigation of drug-
25
delivery dynamics through the cell membrane, early
25 diagnosis of cancer cells, inspection of pollutants and toxi-
cants in the environment, and the detection of exploder
for public safety. However, for most conventional in
situ or in vivo techniques, signals from target molecules
2 RAMAN SPECTROSCOPY
in these systems are either too weak to be detected or
rather difficult to be distinguished from interfering signals
because of the poor energetic resolution. Moreover, many
complex systems require new methods capable of the
real-time detection and high spatial resolution. Thus,
the ultimate goal of analytical science is to continuously
develop methods that promote in situ (in vivo) analysis
to the unprecedented level with ultrahigh sensitivity and
high energetic/spatial/temporal resolutions.
Two years after the report of ‘a new type of secondary
radiation’ from the scattering of focused beams of sunlight
in benzene liquid,(1) Sir C.V. Raman received the Nobel
Prize in Physics ‘for his work on the scattering of light
and for the discovery of the effect named after him’ in
1930. Such a great honor was awarded soon because the
scientific community immediately recognized the great
value of the Raman effect that can be developed into a
powerful fingerprint vibrational spectroscopy, which can
achieve nondestructive, high-resolution, and real-time
detection and are considered outstanding candidates.
Raman spectroscopy relies on inelastic scattering of
light and has many intriguing features in comparison with
other optical spectroscopies. Different from fluorescence
spectroscopy, Raman spectroscopy does not suffer from
the rapid photobleaching, and can provide rich fingerprint
spectra with energy resolution readily up to 1 cm−1 and a
wide spectral window (5–4000 cm−1 ). As a result, Raman
spectroscopy can give much insight into a variety of
static or dynamic processes at the molecular level, e.g.
identification of the structural information and qualitative
determination of the surface bonding, conformation, and
orientation. Water, one of the most important solvents
in analytical chemistry, is a very weak Raman scatterer
but has an intense infrared (IR) absorption. Thus, Raman
spectroscopy is more applicable to study aqueous systems
compared with IR spectroscopy.
All these advantages promise Raman spectroscopy to
be a powerful tool in analytical chemistry. However,
Raman scattering is a two-photon process occurring at
a time scale of about 10−12 s, and the cross section of a
molecule for such a process is about 106 and 1014 times
smaller than those of IR and fluorescence processes,
respectively.(2,3) Therefore, Raman signals are usually
very weak, with typically one Raman photon produced by
108 –1010 incident photons. In the first three decades after
its discovery, Raman spectroscopy was not recognized as
a widely used technique.
To elevate the sensitivity of Raman spectroscopy,
strategies that can enhance either instrumental detecting
ability or photon-molecular interactions have been
adopted. After the invention of laser in the early 1960s,
detection sensitivity of Raman spectroscopy has been
greatly improved with laser as an ultraintense light source.
The use of lasers in the ultraviolet (UV) through to the
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DOI: 10.1002/9780470027318.a9276
near-IR makes Raman spectroscopy a flexible technique
that can analyze the samples of bulk materials (which we
call it normal Raman measurement), ranging from lunar
rocks to ocean ore, from silicon chips to plastics, and from
proteins to drugs at the molecular level.(4 – 7) But with
respect to surface science and ultratrace analysis, where
the number of probe molecules is substantially smaller
than that of bulk materials, the detection sensitivity of
the Raman spectroscopy is still to be improved.
The following equation gives the Raman intensity
expression for a vibrational mode of a molecule following
the Placzek’s polarizability theory with regard to the
instrumental and surface factors.(8)
2 7 π5  2
Imn = I0 (ν0 − νmn )4 |(αρσ )mn | NAQT0 Tm (1)
32 c4 ρσ
where N is the number density of the adsorbate
(molecules cm−2 ), A is the surface area illuminated
by the laser beam (cm2 ),  is the solid angle of the
collection optics (sr), QTm T0 is the product of the detector
efficiency, the throughput of the dispersion system, and
the transmittance of the collection optics. Even if the
probe molecules fully cover a flat surface, the number
of molecules is only about 107 within the laser spot of
about 1 μm in diameter. However, it is still not sufficient
to detect a surface adsorbate with a monolayer coverage
nowadays even with state-of-the-art Raman instruments
through the improvement on QTm T0 . Although the
surface Raman scattering intensity scales linearly with
the incident laser power (I0 ) and the fourth power of
energy (ν0 ), the ultimate sensitivity is limited by the
surface damage threshold of the substrate.
In addition to the optimization of experimental
instrument, an alternative way to increase the intensity
is to choose the molecules that exhibit resonance
Raman scattering (RRS) effect, in which the laser
excitation frequency is equal to or near the frequency
of a molecular chromophore. However, relatively few
molecules have suitable electronic absorption at the
laser excitation wavelength employed, particularly in
the visible region. Furthermore, a strong fluorescence
background will generate with the increase of Raman
signal in RRS. The RRS-to-fluorescence (signal-to-noise)
ratio (S/N) varies dramatically between molecules, which
generally limits the application of RRS. Therefore, due
to the inherent weakness of the scattering mechanism,
Raman spectroscopy had seldom been utilized for the
characterization of surface species before the mid-
1970s.(9)
However, Raman spectroscopy is highly attractive to
surface scientists as it can, in principle, provide much
insight into a variety of chemical, physical, and biological
surfaces and interfaces at the molecular level. Besides,
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
it can be applied to in situ investigation of solid–liquid,
solid–gas, and solid–solid interfaces and processes, to
which many surface techniques are not applicable. These
important advantages have led researchers to seek any
possible methods to exploit Raman spectroscopy to
surface science and related fields, e.g. surface Raman
spectroscopy.
The landmark breakthrough of surface Raman spec-
troscopy lies in the discovery of the SERS effect. In
1974, Fleischmann et al.(10) reported the first in situ
Raman spectroscopic measurement of pyridine adsorbed
on an electrochemically roughened silver electrode. The
Raman spectrum proved to be of very high quality and
evidently was due to a surface species in view of its elec-
trode potential dependency. In retrospect, this was, in
fact, the first SERS measurement, although it was not
recognized as such at that time. The authors initially
thought that the electrochemical roughening procedure
has significantly increased the surface area of the elec-
trode and therefore the number of surface molecules,
so that the intense surface Raman signal of pyridine, a
molecule with very large Raman cross section, can be
obtained. After carefully making the calculation and
experimental verification, Van Duyne and Jeanmaire
claimed that ‘some property of the electrode surface or
the electrode/solution interface is acting to enhance the
effective Raman scattering cross section’, which results
in Raman intensity from adsorbed Py being ‘five to six
orders of magnitude greater than expected’.(11) But their
paper had experienced an exhaustive reviewing proce-
dure as the people tended not to believe it. In 1977, it was
eventually published, and independently Albrecht and
Creighton reported a similar result.(12) They provided
strong evidences to demonstrate that the enormously
strong surface Raman signal must be caused by a true
enhancement of the Raman scattering efficiency itself.
This effect was later named as SERS (Figure 1).
The discovery of SERS impacted in analytical chem-
istry, surface science, and spectroscopy because the
intrinsically low detection sensitivity is no longer a fatal
disadvantage for Raman spectroscopy. Vigorous research
activities have ensured not only in the electrochemical
environment but also in air and under ultrahigh-vacuum
(UHV) conditions on virtually every conceivable metal
surface substrates, colloids, powders, and even catalysts
supported on insulator granules. The SERS effect makes
it possible to use Raman as an in situ diagnostic technique
for the determination of the detailed molecular structure
and orientation of surface species.
Benefiting from its advantages, SERS has been widely
used in a variety of fields such as electrochemistry, life
science, biomedical engineering, environmental science,
and public security.(13) In electrochemistry, SERS can
be used to identify the surface bonding between an
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DOI: 10.1002/9780470027318.a9276
3
991 1005 1025
1030
1037 1036
1008
(a) (b) (c) (d)
1006
1005
1035
1033
(e) (f) (g) (h)
Figure 1 Raman spectra of pyridine (Py) in solution: (a) liquid
Py; (b) 0.05 M aqueous Py; and the SER spectra at the silver
electrode at different potentials: (c) silver electrode 0 V; (d)
−0.2 V; (e) −0.4 V; (f) −0.6 V; (g) −0.8 V; and (h) −1.0 V.
The reference electrode is saturated calomel electrode (SCE).
(Reproduced from Ref. 10. Copyright 1974, Elsevier.)
adsorbate and the electrode, determine the adsorption
sites and molecular configuration, and monitor surface
interactions.(14,15) In life and biomedical sciences, SERS
has been utilized for the direct label-free detection
or as SERS labels for the indirect detection. SERS
has been applied to intracellular monitoring of drug
release, detection of single-base mismatch of DNA,
immunoassays of cancer markers, detection and imaging
of biological cells, and so on.(16) In environmental science
and public security, SERS has been adopted to trace
analysis of a variety of environmental pollutants, high
explosives, and so on.(17,18)
As aforementioned, since the discovery of Raman
spectroscopy, the intention of increasing sensitivity
has been a consistent thread running through all its
developments, which finally leads to the discovery
of SERS.
Significant progress has been made since 39 years after
the first observation and 36 years after the discovery
of SERS. Indeed, a simple search through the ISI Web
of Science® using the keywords ‘SERS’ OR ‘surface
enhanced Raman’ from 1974 to 2012 yields 15 400
papers, including some excellent review articles,(19 – 36)
books,(13,37 – 40) and special issues.(41 – 46) This voluminous
research database provides ample testimony of the
scientific interest on SERS (Figure 2).
However, the advantages and disadvantages of SERS
are both significant. The major disadvantages of SERS
derive from its intrinsic lack of generality and reliability.
For developing into any powerful and versatile
analytical tool, there are always three phases (scopes) of
development from basic research to industrial application.
In the beginning, the method is invented and established,
4 RAMAN SPECTROSCOPY
2000
1600
Number of publication
1200
800
400
0
1980 1984 1988 1992 1996 2000 2004 2008 2012
Year
Figure 2 The number of publications in the 1980–2012 period
searched through the ISI Web of Science® using the keywords
‘SERS’ OR ‘surface enhanced Raman’ from 1974 to 2012.
Fundamental
Resolution Generality
Energetic Materials
Spacial Morphology
Temporal condition
... ...
Ultrahigh-sensitivity !
Figure 3 Three phases (scopes) of development of a new
analytical tool from basic research to industrial application.
which is first recognized in its specific and small scientific
community (e.g. spectroscopy community), then adopted
as a technique by more general and broad science
community (e.g. analytical, surface and material sciences),
and finally widely applied as an instrument in market (e.g.
laboratory and daily life). In each phase, the focusing
issue is very different. The sensitivity and resolution
(which is divided into energetic, spatial, and temporal
resolutions) constitute the key in the first phase. After
that, the generality and versatility are considered the key
in the second phase. Then, the reliability turns to be the
key in the third phase. It is necessary to emphasize that
the ultrasensitivity should always be taken into account
throughout the whole development course, especially for
an analytical tool aiming to trace analysis and surface
(interface) analysis (Figure 3).
In the first phase, ultrahigh detection sensitivity and
resolution may be primarily required.(47,48) In some sense,
SERS does very well in this scope as SERS can provide
high resolution and ultrahigh sensitivity. In the scope of
more general science community, an analytical method
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DOI: 10.1002/9780470027318.a9276
should generally be applied for widespread systems
instead of few systems under few conditions. In the
scope of the market or even human’s daily life, or other
more practical applications, an analytical method should
be reliable, i.e. the data should be well reproducible
and the technique should be easily handled and cost-
effective.
In fact, the latter two criteria (generality and reliability)
were the two major obstacles hampering the development
of SERS in the past three decades. Soon after the
discovery of SERS, it was realized that only few free-
electron metals, mainly Ag, Au, and Cu, provide a
giant SERS effect under the condition that the metal
surface roughness or the colloid size must be at the
scale of several tens of nanometers. Two key stumbling
blocks in applying SERS were perceived to be lack
of material and morphology generalities. The former
severely limited the breadth of practical applications
for SERS in various materials, e.g. Pt, Fe, Ni, and Si,
widely used in electrochemistry, corrosion, catalysis, and
Practical
other industries. The latter confined SERS studies to
surfaces with ill-defined morphology that is not commonly
Reliability acceptable in the community of surface science.
Reproducible The second limitation of SERS mainly stems from
Easy handle the poor spot-to-spot and substrate-to-substrate repro-
Cost effective
...
ducibilities of SERS detection due to the instability of
nanostructure or surface morphology of coinage metals
under laser illumination and the lack of uniformity of the
nanostructures.(49) The lack of reproducibility severely
limits the use of SERS as a quantitative analytical tech-
nique, which hinders it to be sold in the market.
With these disadvantages, the development of SERS
was tortuous. It is, therefore, necessary to get a deep
insight into this abnormal enhancement by developing
relevant theories and rationally designing experiments.
From the discovery of SERS to the mid-1980s,
much attention was paid to achieve the mechanistic
understanding of the enormous enhancement of SERS.
In 1985, Moskovits(19) eloquently summarized that the
enhancement of electromagnetic (EM) due to SPR
dominantly contributed to SERS. Besides, in that period,
the materials of SERS substrates had been expanded
from silver to copper and gold,(50) roughened surfaces
to metallic colloids,(51) and attenuated total reflection
(ATR) configurations to island films.(52,53)
From the mid-1980s to early 1990s, the focus on
SERS research started to move from the fundamental
understanding of SERS phenomenon to the exploration
of promising analytical applications of SERS.(54 – 56) The
initial studies have shown that the main difficulty in SERS
was the lack of reproducibility. Very small variations in
the substrate preparation, even sampling in different areas
of the same substrate, would lead to significant changes
in the SERS spectra. The drawback of reproducibility
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
was partially derived from the ill-defined morphology of
SERS substrate and prevented SERS from being applied
as a quantitative tool, although the application of SERS
for qualitative trace detection was being developed in
several directions, spanning from electrochemical studies
to biosensors.(48)
Boosted by the rapid development of nanoscience in
the 1990s, SERS has attracted a wide interest again since
about 1996 and achieved a second upsurge in the 2000s.
Recalling the development of science during this period,
we will find that the renaissance of SERS is not out
of expectation as SERS is in fact one of the important
branches of the ascendant nanotechnology. It has been
found that SERS activity is critically dependent on the
size, shape, and aggregation of nanoparticles (NPs). A
great variety of techniques of nanoscience have been
employed to synthesize and characterize SERS-related
NPs or nanostructures in a well-controllable state, which
is essentially important to develop SERS. Such efforts
have led to a most significant progress in this field, i.e.
bringing SERS into the forefront with single-molecule
Raman spectroscopy.(57,58)
In 1997, single-molecule surface-enhanced Raman
scattering (SM-SERS) was firstly reported from two
independent groups.(57,58) Kneipp et al.(58) reported
successfully the detection of a single molecule of
crystal violet adsorbed on aggregated silver colloids. On
the other hand, Nie and Emory(57) combined SERS
and resonance Raman effects, i.e. surface-enhanced
resonance Raman spectroscopy (SERRS), to produce the
required sensitivity to detect a dye molecule adsorbed
on the surfaces of an NP cluster. This result has been
considered to be more convincing as a typical SM-SERS
system after performing the systematic studies by many
other groups. High-quality SERS or single molecule
surface-enhanced resonance Raman spectroscopy (SM-
SERRS) spectra from a single molecule adsorbed on well-
characterized silver and gold NPs have been obtained,
with an extraordinary signal enhancement up to ∼1010 ,
which is much higher than the widely accepted value
of 106 for SERS. SM-SERS has improved the molecule
generality and marked SERS as one of the most promising
tools for trace analysis in life and medical sciences as
well as security and environment protection with single-
molecule sensitivity.
In parallel to the achievement with single-molecule
sensitivity, the material generality of SERS has also been
substantially improved. Owing to the development of
various methods for the fabrication of nanostructured
surfaces and the application of the confocal microscope
and the holographic notch filter in Raman instruments,
SERS could be generated directly on electrode surfaces
made from massive transition metals (TM, an element
whose atom has an incomplete d subshell, or which can
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DOI: 10.1002/9780470027318.a9276
5
give rise to cations with an incomplete d subshell) and
their alloys, such as Pt, Pd, Ru, Rh, Fe, Co, and Ni.(59)
The experimental enhancement factors (EFs) of SERS
on these TM substrates range from one to three orders
of magnitude; thus, the severe limitation encountered
in substrate generality of SERS appears to be partially
overcome.(60) However, the EF on pure TM substrates
is so weak that only few types of molecules with large
Raman cross section can be studied, which limits the
molecular generality.
To expand the material and morphology generalities
of SERS, tip-enhanced Raman spectroscopy (TERS)
was invented by several groups in 2000. With TERS,
a nanogap can be formed controllably between an
atomically flat metal surface and the tip with an optimized
shape, within which the enhanced EM field from the
tip can be coupled (borrowed) effectively. Thus, one
can obtain surface Raman signals (TERS signals) from
adsorbed species at Au and Pt single-crystal surfaces. The
EF achieved on these single-crystal surfaces can be up to
106 , especially with a very high spatial resolution down to
about 10 nm.
To the similar goal, shell-isolated nanoparticle-
enhanced Raman spectroscopy (SHINERS) was intro-
duced in 2010, in which the Raman signal amplification is
provided by gold NPs with an ultrathin silica or alumina
shell.(61) A monolayer of such NPs is spread as ‘smart
dust’ over the surface that is to be probed. The ultrathin
coating prevents the NPs from being agglomerated, sepa-
rates them from direct contact with the probed species,
and allows the NPs to conform to different contours of
substrates. High-quality Raman spectra were obtained
from various molecules adsorbed on Pt and Au single-
crystal surfaces and from Si surfaces with hydrogen
monolayers.(61)
The TERS and SHINERS measurements on DNA,
living cells, and citrus fruits with pesticide residues
illustrate that these two new members of the SERS
family significantly expand the flexibility of SERS for
useful applications in the materials and life sciences, as
well as for the inspection of food safety, drugs, explosives,
and environment pollutants. Since 2000, SERS has been
rapidly expanding its horizons in analytical, life, materials,
surface, and forensic sciences.
Owing to the intrinsic multidisciplinary nature with
vibrant activity of SERS, it is almost impossible for us
to completely cover all the areas. This chapter aims at
providing a general introduction on SERS from analytical
and physical aspects, but not intended to simply supplant
the already available exhaustive literature in this field.
From the physical aspect, SERS is nanostructure-related
phenomenon and outcome of multiple interactions of
photon, molecule, and surface. From analytical aspect,
SERS should be systematically considered four criteria,
6 RAMAN SPECTROSCOPY
namely, sensitivity (energetic, spatial, and temporal),
resolution, generality, and reliability.
In the following sections, we first review the working
principles of SERS, with an emphasis on the major
contribution from SPR to the SERS effect. From the
review on SERS mechanism, the further developed
methods on expanding the generality and reliability
are also based on our good understanding of SPR.
We then summarize the methods for the preparation
of SERS substrates and the general procedures of
SERS measurements. After that, we focus on some
recent developments on extending the generality and
reliability of SERS, employing the strategy of ‘borrowing
SERS activity’ by three types of conformations: (i)
chemically synthesize Au NPs coated with ultrathin shells
of various TMs (Section 2.4); (ii) TERS (Section 3), and
(iii) SHINERS (Section 4). We discuss the advantages
and disadvantages for the SERS family members with
special regard to their sensitivity, resolution, generality,
and reliability. Finally, we give some prospects on the
emerging methodologies in view of new SERS substrates,
methods, techniques, and theories.
2 SURFACE-ENHANCED RAMAN
SCATTERING
Specifically speaking, SERS is primarily a phenomenon
associated with the amplification of Raman signals, by
several orders of magnitude, of analytes adsorbed on
or very close to the nanoconfined structures because of
the enhancement of the local EM fields generated such
as by surface plasmon resonance. Alternatively, generally
speaking, SERS effect is that Raman signals are enhanced
when analytes are adsorbed on or very close to certain
substrates whose curvature is in the nanoscale.
SERS can provide rich structural information with
a sensitivity that is comparable to that of fluorescence
and is attractive to be used in analytical chemistry.
Ultralow detection limits, down to the single-molecule
regime,(57,58,62 – 65) are possible with SERS. In addition,
SERS also provides surface selectivity as Raman signals
from analytes only close to SERS-active substrates can
be amplified.
In order to make full use of the SERS effect, especially,
to maintain the advantage of high sensitivity and high-
energy/temporal resolution of SERS and to offset the
weakness of SERS, i.e. the limitation of (material and
morphology) generality and reliability mentioned in the
previous section, it is very important to understand the
working principles of SERS at first.
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DOI: 10.1002/9780470027318.a9276
2.1 Principles of Surface-enhanced Raman Scattering
2.1.1 The Development History of Surface-enhanced
Raman Scattering Mechanisms
At the early stage of SERS, there were several
mechanisms or hypotheses reported on SERS.(13,66 – 68)
It is now well accepted that the enhancement of the local
EM field, especially, the excitation of SPR dominantly
contributes to the giant enhancement of EM field and the
SERS effect.(38,69)
It may be necessary to mention that there are some
other enhancements that are unable to be described by the
EM mechanism based on the classical electrodynamics.
These enhancement mechanisms are mainly related to
surface chemistry and/or photon-driven electron transfer
and are usually classified as chemical effect (CE), which
may be the result of the adsorption-induced modification
of the polarizability of analytes and depend on molecular
specificity.(20,68,70 – 74)
At least, up to now, there is no choice to exclude this
category. That is because Raman intensity is directly
proportional to the square of the derivatives of the
induced dipole with respect to certain vibrational normal-
mode Qk , ∂μind /∂Qk , which in turn equals to the point
product of the molecular polarizability tensor derivatives
∂α/∂Qk and the local EM field strength, Eloc . Therefore,
either the increase of Eloc or the increase of the molecular
specific quantity ∂α/∂Qk will lead to the enhancement of
surface Raman intensity.
The enhanced local EM field comes from the strong
interactions between light (both incident and scattered)
and the nanostructured metallic substrates (typically,
Au, Ag, and Cu), which rarely depend on the specific
molecules adsorbed on the SERS substrates.(75) The
excitation of SPR, especially the localized surface
plasmon resonance (LSPR) version, lighting rod effect,
and the coupling between the two lead to the increase
of EM field in close proximity to the nanostructured
surfaces. The EM coupling of oscillating dipoles of
adsorbed analyte and its image in the presence of
metal surfaces may also contribute to the final Raman
enhancement.
Although the concept that SPR makes the major
contribution to SERS for most of the developed SERS
substrates has been established and is well understood
now, it was not the case when the SERS effect was
discovered and confirmed in the mid-1970s.(19) Surface
plasmon is a quasi-particle describing the collectively
oscillating mode of free electrons gas with long-range
Coulomb correlation in the interfacial nanoconfined
systems.(76) The free-electron materials (typically, Au,
Ag, and Cu) and geometries with interfacial confinement
are the two key substrate-related elements of SP.(77)
Such oscillations lead to narrow regions of enhanced
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
EM field strength that decays exponentially with distance
from the surface (ldecay < 10 nm). The average Raman
enhancement (from regions of greater field strength as
well as from regions of weaker field strength) may be as
high as six orders of magnitude for the nanostructured
coinage metals Au, Ag, and Cu.(19,27,30,78) SERS may
also be obtained from the nanostructured TMs (Pt, Ru,
Rh, Pd, Fe, Co, and Ni) in group VIII-B. These TM
nanostructures yield average enhancements ranging from
one to three orders of magnitude.(29,48)
It was Moskovits,(79) Creighton,(51) Chen,(52)
Chang,(80,81) Pettinger,(50) Gersten,(82,83) Gersten and
Nitzan,(84,85) McCall,(86,87) Kerker,(88 – 90) Metiu,(22,91,92)
and Schatz,(68,93,94) who majorly contributed to the
development of SPR mechanism working for SERS from
the late 1970s to mid-1980s.(19) In 1977, Moskovits and
Hulse(95) studied the mechanism of the colors of the elec-
trodeposited Al2 O3 and attributed it to the embedded
transition metallic colloids with effective medium theory.
Then, he extended this idea to interpret the SERS
effect in 1978, and firstly introduced the concepts of
SPR contribution to SERS and interpreted the opposite
trends of wavelength-dependent SERS intensity from
van Duyne’s and Creighton’s works(96) to the differences
in roughening procedures of silver electrodes.(79) More
importantly, Moskovits(79) even predicted that Ag and
Cu colloids could also support the giant Raman effects,
and even reported the surface selection rules of SERS(97)
before he published a remarkable review in 1985.(19)
In 1979, Creighton et al.(51) published a comprehensive
paper on SERS from Ag/Au colloidal surfaces. In
that paper, Creighton correlated the sizes/materials of
metallic colloids and the wavelength of SPR with SERS,
and pointed that it was the surface plasma resonance
of metallic colloids or Mie scattering that leads to
the giant surface-enhanced Raman effect, which he
called ‘plasma resonance-enhanced Raman’.(51) Finally,
Creighton et al. concluded that the special conditions
of the dielectric functions of the substrates determined
the material specificity for SERS. Creighton’s work on
expanding SERS substrates from roughened electrodes
or deposited surfaces to colloidal surfaces objectively
paved the way to spread the applications of SERS from
surface science to more general community, such as
electrochemistry, heterogeneous catalysis, biochemistry,
and polymer science.
Besides, Creighton et al.(98) further demonstrated
that the aggregation of Ag/Au colloids would lead
to larger enhancement of SERS. The aggregation of
Ag/Au colloids is actually the rudiment of the key
concept of ‘SERS hot spots’. Metiu and coworkers firstly
studied the EM coupling of a nanosphere dimer and the
sphere–plane-coupled structure.(91,99) The importance
of colloid dimer or aggregates has not been well
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7
recognized until the discovery of SM-SERS.(57,58) After
that, scientists paid more attention to the more effective
EM coupling of NPs, which are of great importance in
practical applications of SERS.(63,100,101)
By using the model of semiellipsoid, Gersten and
Nitzan(84) studied the SPR, lightning rod, and adsorbate-
imaging effects in SERS. Schatz(93,94) considered the
assemblies of particles on the surfaces. Then, Kerker
analytically calculated the SERS EFs by the interpolar-
ized model with molecule adsorbed on a metallic sphere.
Kerker(89,102) further considered the key factors of SERS,
such as the size of colloidal particles, the position of
adsorbed molecules, and wavelength of the incident light.
In the aspects of smooth film, Chen(52) theoretically
predicted that two orders of EF could be obtained for
ATR–Raman and ATR–coherent anti-Stokes Raman
spectroscopy (CARS) in 1976. As ATR mode can be
correlated with surface plasmon polariton (SPP), the
development of ATR–Raman practically helped the
scientists to understand SERS on roughened surfaces.
Experimentally, Chang et al. compared ATR–Raman
from Ag-film-coated hemicylindrical prism with surface
Raman spectra from Ag islands, and they demonstrated
the contribution of surface plasmon excitation to SERS
in 1979.(80) Pettinger et al.(50) observed the strong
dependence of surface Raman intensity on exciting
frequency and the angle of incident light for roughened
Au, Ag, and Cu electrodes and obtained the evidence
for the surface plasmon origin of SERS; Tsang et al.(103)
reported similar results but SERS on the surfaces of Ag
grating.
Lombardi,(70) Persson,(104) Otto,(20,105) Efrima and
Metiu,(106,107) Ueba,(108,109) Furtak,(110) Gerstan and
Schatz,(111) Campion,(72) and many others have made
meaningful contributions related to the CE of SERS.
As summarized in Refs 73, 112, and 113, there are five
types of CEs in SERS. (i) Ground state interactions,
such as surface complexation or chemisorption-induced
increase of polarizability in condition of far-away-
from resonance;(112,114 – 117) (ii) resonant or resonance-
like Raman process, such as resonant Raman of free
molecules, chemisorption-induced molecular resonance,
or pre-resonance Raman processes;(118 – 121) (iii) photon-
driven electron transfer from molecules to metal or
the opposite;(71,122 – 124) (iv) transient electron-enriched
states due to extremely negatively applied potential
in electrochemistry(125) or the donation of generated
electrons to analytes; and(126) (v) more polarizable
electronic states under external field, such as some elec-
trochemical SERS, and bias-voltage-enhanced Raman
in molecular junctions.(127,128) It should be noted that
CE in SERS depends on the detailed interaction in
molecule–substrate systems; its general principles and
8 RAMAN SPECTROSCOPY
the enhancement magnitudes should be carefully demon-
strated and detected by rationally designed experiments
in future. Please see the early reviews and books in Refs
13, 66, and 68 for the mechanistic studies on SERS.
SERS effect depends not only on nanostructured
surfaces but also on the interactions between light and
matters (molecules and metallic nanostructures). In other
words, in most cases, SERS involves strong three-body
couplings of photon–molecule–NPs (–nanostructures).
As shown in Figure 4, there have been good quantitative
theories dealing with three scientific branches, i.e.
nanoplasmonics dealing with interaction of photons
with plasmonic nanostructures, molecular spectroscopy
dealing with interaction of photons with molecules, and
surface science dealing with interaction of molecules and
nanostructures. However, SERS sites in the cross area
of photons, molecules, and nanostructures, and is indeed
a type of multidisciplinary science.(113) As there is no
method that can treat these three-body interactions at the
same theoretical level, it is very complex to understand
the unified image of SERS mechanism.
As surface-plasmon-enhanced EM field dominantly
contributes to most cases of SERS, in the following
section, we will focus on the EM mechanism of SERS.
2.1.2 The Electromagnetic Mechanism of
Surface-enhanced Raman Scattering(37,38,77)
First, in a nutshell, we use a model with molecules
adsorbed on the surface of a small gold nanosphere as
an example to understand SPR and SERS.(38,77) If the
radius of a metallic sphere, a is much smaller than the
wavelength of the incident light (a/λ < 0.1), the response
of the sphere to the external field can be simplified as an
Surface-enhanced Raman spectroscopy
Photon
on
Molecular
spectroscopy
Nanostructu
ure
u
Molecule
Nano-surface science
Figure 4 Schematic illustration of many-body interac-
tions of photon–molecule, photon–nanostructure, molecule–
nanostructure, and photon–molecule–nanostructure.
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induced dipole p
p = ε0 εm g0 E0 (2)
where ε0 is the vacuum permittivity, εm is the dielectric
constant of the surrounding medium, E0 is the incident
electric field in frequency ω0 , and g0 can be expressed as
ε(ω0 ) − εm
g0 = (3)
ε(ω0 ) + 2εm
The electric field strength inside Ein and outside Eout
of Au nanosphere are
3εm
Ein = E (4a)
ε(ω0 ) + 2εm 0
3n(n • p) − p
Eout = E0 + (4b)
4πε0 εm r3
As we can see, g0 , Ein , and Eout can reach to their
maxima as long as the denominator term (ε (ω0 ) + 2εm )
gets close to ZERO,
Re[ε] + 2 εm → 0, and Im[ε] → 0 (5)
In other words, the real part of dielectric function
of the metal, Re[ε], should be negative and close to
the negative twice value of the dielectric constant of
the surrounding medium εm , whereas the imaginary
part of the dielectric function of the metal, Im[ε],
should be positive but very small. Fortunately, free-
electron metals, such as Ag, Au, and Cu, fulfill these
conditions well in the visible regime, whereas TMs do
not.(59,129,130) At the resonant condition, the conducting-
band electrons can be coherently excited and collectively
oscillated around the background ion cores in the
presence of interfacial metal–dielectric nanostructured
boundaries. This collective-motion mode of electrons can
be quantized as surface plasmon.(76,131 – 136)
At the resonant condition, the molecules get directly
adsorbed on or get very close to the nanostructured
surfaces, which will be polarized by the enhanced local
optical field, and create a induced dipole oscillating
Nano- in the Raman-shifted frequency ωR (= ω0 –ωk , where
plasmonics
ωk is the vibrational frequency of the kth normal
mode), which will further polarize the Au NPs. Au NPs
will finally reirradiate into far field (in frequency ωR )
where a detector sites. According to optical reciprocal
theorem, the re-irradiation process will win the second
enhancement at the Raman-shifted frequency. Therefore,
the total enhancement in the small particle approximation
is ∼4|g0 |2 |g|2 .(63,89,137)
|Eloc (ω0 )|2 |E(ωR )|2
G = G(ω0 )G (ωR ) ≈ (6)
|E0 (ω0 )|2 |E0 (ωR )|2
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
where
ε(ωR ) − εm
g=
ε(ωR ) + 2εm
Usually for low-frequency vibrational normal modes
of adsorbed molecules, ω0 ∼ ωR , g ∼ g0 , and the total EF
can be further approximated to be 4|g0 |4 . That is why the
EFs of SERS, G, can be approximated as
|Eloc (ω0 )|4
G = G(ω0 )G (ωR ) ≈
|E0 (ω0 )|4
In summary, as shown in Figure 5(a), there are two
steps of enhancement during the process of SERS. The
first step is the enhancement of the incident local field
because of the excitation of SPR. Here, the Au NP
works as a receiving optical antenna to transform far field
(in frequency ω0 ) to near field. The second step is the
enhancement of far field in certain range of solid angles.
Here, the Au NP works as a transmitting optical antenna
to transform near field in the Raman-shifted frequency
ωR to far field.(63,89,137)
In the case of NP dimer (Figure 5b), owing to the strong
coupling of two dipolar plasmons, the optical local field
in the gap between two NPs will be extremely intense in
contrast to single NP, which can even support SM-SERS
detection (please see the details in Section 2.4.1).
Overall, SERS is the effect of plasmon-enhanced
Raman scattering; any nanostructure possessing the
features of exciting SPR in the visible and near-IR regimes
can support SERS as well. Optimization of the key factors
of SPR and Raman will help us to optimize the conditions
of SERS.
SPR + Raman = SERS
Receiving antenna
Ein(r′,ω 0) Ep(r′,ω 0) = ELM(r′,ω 0) + Ein(r′,ω 0)
ER(r,ω 0−ω i) = Esc(r,ω 0−ω i) + Edip(r,ω 0−ω i)
Transmitting antenna
(a) Single nanoparticle
Figure 5 The working principles of SERS from Au nanosphere monomer (a) and dimer (b).(113)
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9
2.1.3 Key Factors Influencing Surface Plasmon
Resonance and Surface-enhanced Raman
(7)
Scattering
2.1.3.1 Material Dependence The key materials
supporting SPR are always called plasmonic materials,
which have a real dielectric function εr with negative
value and an imaginary dielectric function εim with posi-
tive but very small value. The coinage metals (gold, silver,
and copper) are the commonly used plasmonic materials
(8) that can be prepared into nanostructures for SPR and
SERS applications.
Besides the coinage metal, alkali metals (Li, Na, K, Rb,
and Cs) and Al can also work as plasmonic materials, but
it is very hard to prepare a stable nanostructured surfaces
composed of these chemically active materials. Al is a
typical plasmonic material in the UV regime.(129,130,138)
Ga, In, Pt, Rh, their alloys, and some complex materials
such as TiN have also been explored as plasmonic
materials.(139)
2.1.3.2 Wavelength Dependence It should be noted
that the SERS effect of coinage metals could not
take place in too short-wavelength regime because
of the interband transitions that make the incoming
optical field be transformed into heat instead of
enhancing near field and irradiating into far field.
Typical working wavelength regimes of Al, Ag, Au,
and Cu are 150–400 nm, 320–1240 nm, 570–1240 nm, and
600–1240 nm, respectively. The requirement for short end
is rigorous, and that for long end is loose.
In order to obtain SER spectra with EFs as large
as possible, typically, the excitation and the scattering
wavelengths should be present at the two sides of a
Hot spot
(b) Dimer or aggreates
10
extinction peak of SPR. Van Duyne et al. have reported
that the best excitation wavelength should be a little bit
lesser than that of LSPR. The displacement between the
two could be ideally a half of the vibrational frequency
of a certain normal mode.(27,78) If the extinction spectra
of a SERS substrate has two SPR bands, which are
close to each other, then we can choose excitation
wavelength as the shorter bands of SPR. This type
of substrates is usually called double-resonance SERS
substrates.(140)
As we see from Equation (1), Raman intensity is
proportional to the fourth power of incident frequency;
therefore, shorter wavelength laser, even UV laser could
be preferable as the excitation laser. In addition, we can
choose the excitation wavelength corresponding to the
molecular absorption and can make use of the resonant
Raman effect to further increase the sensitivity and avoid
the interference of fluorescence background. However,
as discussed earlier, SERS substrates cannot work in too
short wavelength. Therefore, we should take into account
all of the factors, e.g. the optimized wavelength of SPR
and molecular resonance, to get the optimum SERS or
SERRS sensitivity.
2.1.3.3 Size and Shape of the Nanoparticles The SPR
of individual plasmonic NP strongly depends on the size
and shape of NP. For instance, the larger the NP is, the
longer the wavelength of the dipolar surface plasmon is.
For much larger NPs, new bands for some multipolar
modes will appear in the short-wavelength range and
the dipolar band in the long-wavelength range will be
damped. For much smaller NPs, absorption instead of
scattering cross section will dominate the total extinction,
which is not preferable for SERS. Typically, the size of
NPs synthesized for SERS should be less than 150 nm and
larger than 20 nm.
By controlling the composition, the size of core, and
shell thickness of core–shell NPs, the peak position of
SPR can be well tailored for SERS and surface-enhanced
infrared absorption spectroscopy (SE-IRAS); please see
the excellent review by Halas et al.(141)
If the NP is not a sphere, there will be several surface
plasmon modes. For instance, for ellipsoidal Au NPs,
there are always at least two types of peaks, one is the
transverse dipolar mode with shorter wavelength, and
the other is the longitudinal dipolar mode with longer
wavelength.(142,143) Regarding the shape dependence
on SERS, for simplicity, we can compare the SERS
performances of an isolated Ag nanosphere and Ag
nanoprolate in Figure 6(a) and (b). As we can see, the
maximum and average SERS EFs (Gmax , <G>) of Ag
nanoprolate are larger than those of Ag nanosphere.(144)
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RAMAN SPECTROSCOPY
Moreover, the distribution of EM field of high-aspect-
ratio nanoellipsoid is more localized than that of low-
aspect-ratio counterparts.(145)
However, SERS EFs of most individual particles except
that with spikes (nanostar) are too small to be used. Ag or
Au dimer, trimer, or other aggregates are more preferable
to SERS. For Au dimer, the ideal size for SERS could
be 120 nm. However, one should make balance with the
ease, monodispersion, yield, and so on of the synthesis of
the NPs in practice.
2.1.3.4 Electromagnetic Coupling in Nanoparticles
Dimer and Aggregates In the coupled-NP systems,
the distance between the NPs plays a key role in the
enhancement of local-field and SERS EFs. As shown in
Figure 7, the smaller the gap size of gold nanospheres
dimers is, the more extinction peaks red-shift, the
stronger extinction intensity becomes, and the larger the
maximum SERS EF gets. It is worth noting that, for
short gap size, the maximum EFs, Gmax increase much
more quickly than the increase of extinction coefficient.
More importantly, when the gap gets close to 1–2 nm,
Gmax in the gap can reach up to 1010 , even for SM-SERS
detection.
However, if the amount of the gap goes to
subnanometer level (< 0.5 nm), the wave functions of
the two separate NPs will overlapped, which results in
a decrease in the local EM and SERS enhancement.(147)
In the subnanometer gap regime, the distribution of EM
field of the dimer NPs cannot be calculated by classical
electrodynamics, then the quantum corrections should be
considered.(148) If the two NPs get touched to each other,
a lower energy mode, charge-transfer mode appears in
IR regime.(148,149)
2.1.3.5 Polarization of Incident Light on Surface-
enhanced Raman Scattering In the plasmonic systems
with anisotropic geometries, especially for the coupled NP
systems, the SERS enhancement will sensitively depend
on the polarization of the incident light. For a nanodimer,
the SERS enhancement with the polarization along the
interparticle axis will be much larger than that with the
polarization perpendicular to the interparticle axis.(150)
2.1.3.6 Location of Analytes at Surface-enhanced Raman
Scattering Hot Spots For a small metal sphere, the
EM field decays exponentially with 1/(R + d)3 , where
R and d are the radius of the sphere and the distance
between the molecules and the surface of plasmonic
NP. Accordingly, the average EF of SERS decays very
rapidly as 1/(R + d)10 . For the systems with strong EM
coupling, SERS intensity decays more rapidly. Therefore,
only molecules adsorbed on or very close to the SERS
substrates can gain a giant enhancement from SERS. For
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION 11

5×104 G max = 4.8×104 Log10 (G)

<G> = 1.1×104 4
4×104 G max/<G> = 4.3

3×104
3.5
p (G>G max/10)
2×104 = 52%
σ 80 = 35% 3
1×104
E
0
−30 −20 −10 0 10 20 30 k 2.5
Arc length from hot spot, L (nm)
3×107
7
G max = 2.6×107 6.5
<G> = 6.6×105
2×107 G max/<G> = 39 6
5.5
p (G>G max/10) 5
1×107 = 68%
4.5
σ 80 = 12%
4
0 3.5
−30 −20 −10 0 10 20 30
Arc length from hot spot, L (nm) 3

9
5×104 9
G max = 4.9×10 8
7
4×104 <G> = 1.54×10
G max/<G> = 140 7
3×104
6
2×104 σ 80 = 0.59% 5
p(G>G max/10)
= 0.68%
1×104 4

3
−30 −20 −10 0 10 20 30
Arc length from hot spot, L (nm) 2

λ = 559 nm

Colloid
2 nm

108 107 106

105
Enhancement factors
on the surface:

Figure 6 Examples of calculated EF (G) distributions around hot spots for two-model SERS substrates immersed in water: (a) a
silver sphere (radius 30 nm), (b) a silver prolate spheroid (radii 20 and 60 nm) representative of elongated or tip-containing NPs, (c)
a silver dimer of spheres (radius 30 nm, gap 2 nm) and (d) G distribution in the region of the gap (2 nm) between two gold colloids
(radii = 30 nm) (for polarization along the vertical axis of the dimer). The most important characteristics of the hot spot are indicated
in each case: maximum SERS EF, Gmax , averaged SERS EF <G> (over the entire particle). (Reproduced with permission from
Ref. 144, (copyright 2012, Annual Reviews) and Ref 146 (Copyright 2008, Royal Society of Chemistry.)

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12 RAMAN SPECTROSCOPY

SERS EF, varying gap, g

z 1012 1012
a 1 nm
1011 1011

Einc 1010 1010

SERS EF, F 0E4, on surface in gap

g 2 nm
k 109 109
θ 3 nm
x
108 108
(a) 5 nm
107 107
<F> (g = 2 nm)
Extinction coefficient, Q NPExt

Extinction, varying gap, g 106 106

10 nm
1 nm
10 105 105
3 nm
20 nm
104 104
10 nm
5 103 103
Single
sphere
102 102
Single sphere
0 101 101
400 500 600 700 800 900 400 500 600 700 800 900
(b) Wavelength (nm) (c) Wavelength (nm)

Figure 7 Schematic configuration of a dimer formed by two spheres of radii a and separated by a gap g. The incoming wave is
polarized along z (axis of the dimer) and with wave vector k along x. (b) Extinction coefficients for varying gaps as functions of
incident wavelength. (c) SERS EF (EF) ∼ (Eloc /E0 )4 at the point on the surface in the gap (on the dimer axis), i.e. at the ‘hot spot’.
Also shown (thick dashed line) is the average SERS EF,<(Eloc /E0 )4 >, in the case of a n = 2 nm gap. (Reproduced by permission of
Wiley, from Le Ru et al.(38) )

the SERS substrates of core–shell nanostructures with a coupled particles, which results in a relative poor spatial
plasmonic core and a dielectric or SERS-inactive shell, resolution.
the shell should be controlled as thin as possible (<4 nm) In addition to the factors listed earlier, the dielectric
to maintain enough enhancement of the localized EM constants of the surrounding medium can also influence
field for SERS. SPR and Raman. That is why SPR can be used for sensors
For coupled plasmonic substrates, SERS hot spots are that are applied in biologic systems and environment
usually in the gap between two or more particles.(151,152) science.(153 – 156)
Figure 6(d) shows that the SERS EFs decay exponentially
from the very gap regime to a distance along the surfaces. 2.2 Methods for Preparing Surface-enhanced Raman
And the surface area supporting maximum SERS EF (up Scattering Substrates
to 108 ) is very small, whereas that supporting intermediate
SERS EF (one to two orders weaker than 108 ) is much Whether SERS can achieve a broader application really
depends on its sensitivity and the reproducibility.(49) Ever
larger. Therefore, the special features of gap hot spots
since the first observation of SERS on an electrochemi-
result in a long-tail probability distribution for SERS
cally roughened Ag electrode, the preparation methods of
detection.
SERS substrates have gone through the following stages:
The field distribution around SERS hot spots also (i) random and nonuniform substrates prepared by elec-
determines the spatial distribution of the Raman trochemical oxidation and reduction cycles (EC-ORCs)
intensities from the adsorbed molecules, i.e. the spatial or vacuum deposition methods; (ii) NPs sols, aggregates,
resolution of SERS. As we can see from Figure 6(c) and and films; (iii) ordered NP arrays obtained through self-
(d), assuming that the molecules are uniformly adsorbed assembly; and (iv) large-area surface nanostructures with
on each NPs, what we really detect from nanosphere defined size, shape, and interparticle spacing prepared by
dimer is the molecular Raman signals from the gap regime template methods and lithographic methods. It is inter-
within 5 nm in distance. However, for single particles, esting to find that the preparation of SERS substrates
the field distribution is more delocalized than that for actually developed follows the trend of random and

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SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
nonuniform substrates to well-ordered nanostructured
substrates and then to well-controlled nanostructured
substrates.
2.2.1 Electrochemical Oxidation and Reduction Cycle
and Vacuum Deposition
The first SER spectra were obtained on a roughened
silver surface prepared by EC-ORC (Figure 8a).(10) Using
this method, one can easily obtain SERS-active coinage
metal and TM surfaces.(29) The common EF achieved
using this method can be as high as 104 –106 for Ag,
Au, and Cu, and 101 –104 for other TM substrates, such
as Fe, Co, Ni, Rh, Pd, and Pt.(165) In parallel to EC-
ORC, vacuum deposition is another commonly used
method to fabricate rough metal film or discontinuous
metal islands to be used as SERS-active substrates
(Figure 8b).(158,166 – 168) Both of these two methods are
simple, but the as-prepared substrate has a randomly
structured surface. Therefore, they lack spot-to-spot and
substrate-to-substrate reproducibilities in their SERS
response.
2.2.2 Chemically Synthesized Nanoparticles
With the vast development of nanoscience and nanotech-
nology, metal NPs of different sizes and shapes have
been synthesized. In 1979, Creighton et al.(51) , for the first
time, applied Ag and Au sols as SERS-active substrates.
Since then, Au and Ag sols have been widely used as
SERS-active substrates (Figure 8g).
(a) (b) (c) (d) (e)
200 nm
Top down
1974 1977 1979 1995 1997 2000
1980 1990 2000
Bottom up
(g) (h) (i) (j) (k)
Figure 8 Timeline of development of SERS substrates
discussed in this article. (a–d) are SERS-active substrates
fabricated via the top-down approaches, (a) EC-ORC;(157)
(b) vacuum deposition;(158) (c) lithographic technique;(159)
(d) electrochemical etching;(48) (e) electromigration;(160) (f)
lithographic technique.(161) (g)–(i) are SERS-active substrate
fabricated via bottom-up approaches, (g) Au colloids;(162) (h)
NP aggregates;(158) (i) Ag NP aggregate for SM-SERS;(57) (j)
NP arrays fabricated by nanosphere lithography;(163) (k) NP
dimmers;(164) and (l) core–shell NPs.(61)
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13
In addition, the addition of a high concentration
of probe molecules or some salts (such as NaCl) in
sols can lead to the aggregation of NPs, which will
improve the SERS activity. A more common method
is to directly disperse the NP sol on a solid substrate to
form NP aggregates or a compact layer of NPs with
effective EM coupling between NPs. In 1995, Natan
et al. firstly reported that Au and Ag NPs adsorbed
on organosilane–polymer-modified Si substrate could be
used as SERS-active substrate (Figure 8h).(169) After
that, this method was widely used in many other
systems. Among the various types of NP aggregates, NP
dimer is a representative one and has been extensively
investigated.(164) It has been discussed in Section 2.1.3
that hot spots are usually generated in the nanogaps or
junctions of NP dimers. Xia et al.(164) describes a one-
pot method that generates dimers of silver nanospheres
by introducing NaCl into the reaction solution; see
Figure 8(k).
As aforementioned, metallic NPs can be used as SERS-
active substrates to directly detect molecular structural
information.(170,171) Meanwhile, they can also be adopted
as labels in the indirect detection process. Typically, the
molecules used as a Raman marker, usually with resonant
Raman activity are adsorbed on the NP surface. Then, the
surface is further coated with a biocompatible shell with
a weak Raman signal (SiO2 , for example). Afterwards,
some molecules that can specifically interact with the
target molecules (antibody–antigen, biotin–avidin, and
aptamer–protein-specific interactions) are linked to the
inert layer. Finally, the modified NPs can be used for
indirect quantitative analysis of the target molecule by
detecting the SERS signal of the Raman marker.
(f)
2.2.3 Lithography
The lithographic techniques have been employed to
prepare large-area, well-ordered SERS substrates. In
2010 1981, Liao et al.(159) fabricated Ag NP arrays by
evaporating Ag onto the microlithography-fabricated
SiO2 post (Figure 8c). Limited by the nanotechnology
at that time, most lithographic techniques were not
(l)
capable of producing nanopatterns with feature sizes
small enough to be truly SERS-active. Currently, electron
beam lithography (EBL) is one of the most powerful
lithographic methods, which has been used to fabricate
structural features as small as 15 nm and can produce
smaller structures (∼5 nm) in exceptional cases. The
EBL method allows the preparation of highly ordered
and uniform SERS substrates with nanostructures having
a wide diversity of shapes and geometries (Figure 8e
and 8f).(172) However, EBL is time-consuming and cost-
ineffective for commercialization.
14
Drop coat
nanospheres
Electro-
200 nm 20 nm deposition
deposition deposition Sphere Sphere
removal removal
FON Nanoarticle array Nanovoid array
Figure 9 Nanosphere lithography for the fabrication of
ordered nanostructured SERS-active substrates. (Reproduced
with permission from Ref. 173. Copyright 2007, Royal Society
of Chemistry.)
Another lithography technique is the nanosphere
lithography.(163,173) In this method, a monolayer or a
multilayer of the highly ordered nanosphere film is
used as the template for the vacuum deposition or
electrochemical deposition. As a result, three kinds of
structured SERS substrates can be produced: (i) physical
vapor deposition on the nanosphere template leads
to the formation of a metal ‘film over nanosphere’
(FON) surface; (ii) after nanospheres in the FON
substrate are removed, triangular NPs arrays can be
obtained (Figure 8j); (iii) the electrochemical deposition
followed by the removal of the nanosphere leaves a thin
nanostructured film containing a regular hexagonal array
of uniform metal nanoislands, nanobowls, and nanovoids
depending on the thickness of the deposited film. The
advantage of the nanosphere lithography method is that
the shape, size, and spacing of the nanostructures can be
controlled by the size of the nanospheres and the thickness
of the deposited metal, so that the peak position of LSPR
can be adjusted to match the excitation wavelength and
achieve an optimized SERS enhancement. As defects are
inherent and unavoidable for the nanosphere lithography,
it is extremely challenging to obtain an ordered surface
without point or line defects. However, with the help
of a microscope, it is still quite easy to find an ordered
area for the quantitative analysis with reasonably good
reproducibility and stability (Figure 9).
2.3 Measurement Procedures of Surface-enhanced
Raman Scattering
SERS is the outcome of multiple interactions of photon,
molecule, and nanostructure surface. The observed SERS
spectrum is the result of multiple factors, and the
contribution of these factors is specific case by case. It is,
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RAMAN SPECTROSCOPY
therefore, essential to have a layout of the experimental
procedure of a SERS study, and analyze closely every
parameter and design the variants in the experiment.
As shown in Figure 10, the whole procedure can be
divided into three parts. (i) Preparation, which includes
the fabrication and surface cleaning of SERS-active
substrate, adsorption of target/probe molecules, and
normal Raman measurement. (ii) SERS measurement
with emphasis on the sensitivity and resolution (including
energetic, temporal, and spacial resolutions). (iii) Data
analysis.
2.3.1 Preparation
Before a new SERS study, a suitable SERS-active
substrate should be obtained first. The fabrication of
various SERS substrates has been discussed in Section 2.2.
In addition, it is important to obtain the normal Raman
spectrum of the species in its original form, such as the
pure liquid, solid, or even some standard samples for the
expected reaction product and then to obtain the Raman
spectrum in the solution to be measured, if possible,
during the in situ study. A good-quality spectrum will
serve as the reference to compare with the surface Raman
spectra. If the spectrum is too complex, an isotopic study
could be employed for the identification of vibrational
normal modes.
Surface cleaning is an important step but often ignored
by many researchers. During the fabrication of SERS
substrate, impurities, such as reductants, surfactants,
or other contaminants, may occupy the surface-active
sites. Therefore, steps focusing on surface cleaning of
SERS substrate should be adopted. For chemically
synthesized NP sols, one can use centrifugation to
remove the unreacted reductants or the surfactants. For
a conductive SERS substrate, electrochemical method
can be employed for surface cleaning. For instance, by
applying a high negative potential, the surface adsorbate
can be desorbed from the surface, leaving a clean surface.
For organic impurities, one can clean the substrates in a
vacuum with oxygen plasma. This method is especially
suitable for nonmetallic surfaces, but should not be
applied to a metal surface, such as Ag substrate, because
of the oxidation of the metal surface by oxygen plasma.
Additionally, the surface can also be cleaned using
competitive chemical adsorption. For instance, iodide
was used to replace surface impurities to obtain a clean
and fresh surface.(174)
After that, the substrate can be used for the adsorption
of target molecules. Generally, this step is performed
by immersion of SERS-active substrate in the solution
of target molecules. The concentrations of the target
molecule and adsorption time depend on the property
of molecules and experimental purpose. In case target
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
Preparation of SERS-
active substrates
Surface cleaning;
target molecule
adsorption
Optimization of
detection sensitivity
Temporal resolution
Data analysis:
e.g band assignment;
EF calculation;
Theoretical calculation
Figure 10 A layout of the measurement procedure for an SERS study.
molecules that have no affinity or even repel with the
substrate, one could adjust their interactions by changing
the surface potential by applying voltage, adding salts or
other electrolytes, or modifying some specific molecules
that can link or attract the target molecules.
2.3.2 Optimization of Detection Sensitivity
To achieve high sensitivity, instrument factors such as
laser wavelength, laser power, and spectral acquisition
time should be optimized in an integrative manner.
For information on choosing of wavelength, please
refer Section 2.1.3. According to Equation (1), high-
power incident light would be preferable for Raman
detection. However, the ultimate sensitivity is limited by
the surface damage threshold of the substrate with respect
to I0 . Regarding the spectral acquisition time, the use of
longer spectral acquisition time and relative low-power
laser can improve the S/N and reliability of the SERS
spectra if one is not interested in time series analysis.
2.3.3 Resolution
Temporal resolution is an important issue that should be
taken into account when one studies a surface (interfacial)
kinetic process. High temporal resolution is helpful to
obtain information on changes in the molecular structure
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15
Normal Raman
measurement
Preparation
Measurement
Spatial resolution
analysis
Data
and surface interaction. For example, some transient
techniques can be combined with SERS for understanding
the surface kinetics and the reconstructuring the process
of surface layer.(175)
Moreover, the time-dependent SERS study is very
helpful to check the stability of a SERS-active substrate.
Most SERS-active substrates suffer the instability and
irreversibility. The SERS intensity may decrease with
time because of the decomposition, then irreversible loss,
of the unstable SERS-active sites (hot spots). Laser-
induced sample damage is another cause of decrease of
SERS substrate activity. Roughened surface makes SERS
substrate be more easily affected by severe heating or
damage effects during the laser irradiation. The extent of
these problems can range from subtle color, or crystalline
changes in the materials, to the complete ablation of
the sample beneath the microscope objective. Therefore,
to avoid the misunderstanding of experimental results
during the SERS measurement, one should first make
sure that the substrate and surface-modified molecules
are stable enough with respect to time during the whole
experiment.
The spatial resolution can be classified into two types:
the lateral resolution and the vertical resolution. Lateral
resolution of about 1–2 μm can be achieved in confocal
Raman systems, which is determined by the size of the
laser spot and the stepping resolution of the X–Y scanning
16
stage. X–Y spatially resolved measurements provide
more reliable and complete information on the surface,
especially for the nonuniform surfaces. This is also useful
for electrode surfaces that change either chemically or
topographically in a microzone upon the variation of
the potential. It is necessary to point out that there are
two types of nonuniform surfaces: (i) the surface only
has few small specific areas that are different from the
major uniform area in terms of chemical composition
and (ii) the whole surface is nonuniform and composes
several different chemical structures. In the first case, one
can just use the micropositioning X–Y stage to move
a specific area of interest to the focused laser spot and
then take the spectrum. This method has been used often
for studying corrosion pits at the electrode surface. If
the surface is arranged spatially with various molecular
species or chemical composites, the whole surface area
needs to be analyzed. In that case, imaging technique
should be applied, and this strategy can be classified into
two categories, referred to as point-by-point mapping and
global imaging.
High vertical spatial resolution is helpful for obtaining
information on molecular distribution in Y-axis. When
a laser spot is focused on the substrate surface, the
Raman signal is mainly contributed by the adsorbed
species. However, when the position of the focus is
above the surface, the Raman signal mainly comes from
the bulk species. Thus, by adjusting the focal point at
different heights above the substrate surface, one can
get a concentration gradient of different solution species
based on their spectral signals.
To increase the spectral (energetic) resolution, one
should consider the instrument factors such as slit and
the length of the optical path of the dispersion elements
(gratings). Using a narrower slit results in higher spectral
resolution. Sometimes, different vibrational modes in
SERS spectrum can overlap with each other. In that
case, one may consider an isotopic labeling experiment
to distinguish these signals and then identify each surface
species.
It should be noticed that all the three kinds of
resolutions are mutually restricted with each other.
Increase in either kind of resolution will lead to the
decrease of signal intensity and thus the other two
kinds of resolutions. For example, the increase of the
spectral resolution by applying a narrower slit will
scarify the signal intensity. Therefore, weak signals may
become indistinguishable from the background noise.
As a result, its temporal and spatial resolutions will
have to decrease. Therefore, it is impractical to achieve
the best performance for all these three resolutions
simultaneously, and there must be some trade-offs
according to the experimental purpose. The only solution
to this problem is to find a way to increase the
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RAMAN SPECTROSCOPY
detection sensitivity. Accordingly, the sensitivity is the
most important issue for SERS measurement. Only after
optimizing the sensitivity, one can fully take advantage
of Raman spectroscopy with high spectral, temporal, and
spatial solutions.
2.3.4 Data Analysis and Enhancement Factor
Calculation
Regarding the assignment of SERS bands, if the
target molecule is known, one can refer to its normal
Raman spectrum or previous literatures to identify
each vibrational mode. Nevertheless, SERS spectra
could be dramatically different from the normal Raman
spectrum because of the surface selection rule and various
adsorption configurations. Therefore, the simulation of
Raman spectra by (time-dependent) density-functional
theory (TD)-DFT is essentially important to analyze the
data and interpret experimental results. The calculation
of the EF is important for SERS applications, which is
discussed in Section 2.3.5.
If the target molecule is unknown, some other analytical
methods such as nuclear magnetic resonance (NMR) or
mass spectroscopy can be used to give a systemic analysis
of the sample. This hyphenated technique is helpful to
identify the element composition and structure of the
analyte.
2.3.5 Calculation of the Enhancement Factor
The calculation of the EF is of great importance,
especially, for the analytical application of SERS. With
the application of SERS in single-molecule detection and
analytical sciences, different types of surface EFs have
been proposed, for example, single-molecule surface EF,
analytical surface EF, and averaged surface enhancement
factor (ASEF). The first of these is only related to the
enhancement of a single molecule sitting at the special
sites, such as a hot spot. Therefore, the single-molecule
surface EF is determined by the morphology of the
substrates, the position of the probe molecule at the
hot spot, the orientation of the molecules, as well as the
polarization of the laser. It reflects the optical properties
of the special surface site, which can be correlated
with the theoretical result. The analytical surface EF
is related to the SERS enhancement of analytes of
known concentration. In this case, the signal intensity
is the major concern and all the analytes are supposed to
contribute to the final SERS signal. It neglects the fact
that SERS is a kind of surface-sensitive phenomenon: only
those molecules adsorbed on the surface experience the
highest EM enhancement, and the enhancement decays
exponentially with the increase in the distance to the
surface. Therefore, it cannot reflect the real enhancement
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
effect of the substrate. Apparently, these two kinds of
EFs reflect a special kind of EM enhancement effect and
have little general application. Therefore, the ASEF that
can really reflect the global enhancement of the substrate
is more important.(176 – 178) The ASEF can be calculated
by taking the ratio of the SERS signal contributed by a
surface-adsorbed molecule to the normal Raman signal
contributed by a molecule in solution or in the bulk.
Isurf /Nsurf
G=
Ibulk /Nbulk
where Isurf and Ibulk denote the integrated intensities
for the strongest band of the surface and bulk species,
respectively, and Nsurf and Nbulk represent the number
of the corresponding surface and bulk molecules,
respectively, effectively excited by a laser beam. Please
refer Refs 157 and 176 for the detailed illustration on this
topic.
2.4 Utilization of the Strength and Offset of the
Weakness of Surface-enhanced Raman Scattering
Generally speaking, SERS is a surface-plasmon-enhanced
Raman effect,(51,79,179) or it can simply be expressed as
SERS = SPR + Raman
As given in Table 1, SERS, on the one hand, integrates
the advantages of energetic resolution and molecular
generality from Raman and the advantages of high
sensitivity from SPR. On the other hand, SERS also
inherits the limitations of SPR, such as only a few free-
electron metals, mainly Ag, Au, and Cu, provide a large
SPR/SERS effect under the condition that roughness of
the metal surfaces or the size of the metal colloids should
be at the scale of tens of nanometers. The necessary
materials for SERS make up material generality, whereas
the necessary condition of the nanostructured surfaces
for SERS makes up the morphology generality.
Table 1 Integration of advantages of SPR and Raman with those of SERS
SPR
Sensitivity Excellent
Single molecule
Energetic resolution Poor
10−2 eV
Spatial resolution Good
1 μm
Time resolution Excellent
10−11 s
Material generality Poor
Au, Ag, Cu
Morphology generality Poor nanostructures
Molecular generality Good
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17
In retrospect, the development of SERS generally
followed two trends. On the one hand, fundamentally,
scientists are keen to increase the sensitivity of SERS
(utilize its strength) to achieve single-molecule detection,
which is ultimate ‘Holy Grail’ in chemical analysis. On
the other hand, practically, in order to make full use of
SERS in real-world applications, its intrinsic limitation
(lack of generality and reliability) must be offset.
(9) 2.4.1 Single-molecule Surface-enhanced Raman
Scattering
SM-SERS has improved the molecule generality and
marked SERS as one of the most promising tools for trace
analysis in life and medical sciences as well as security and
environment protection with single-molecule sensitivity.
Since its discovery, many SM-SERS results have been
reported, but there are still some controversies. The major
points in these discussions are the reliable proof of the
single-molecule nature of the detected SERS spectrum
and the upper limit of the EF under SERS conditions.
The initial reports on SM-SERS were based on the
idea of ultralow-concentration studies: if one dilutes the
concentration of molecules so that there is average one
(or less than one) molecule in the scattering volume, the
only signals that are observed are attributed to SM cases.
However, researchers soon found serious limitations in
terms of statistical soundness. That is because when
molecules are adsorbed on a metallic substrate, they
typically result in a highly nonuniform molecular density.
For example, in a colloidal solution, many molecules can
be absorbed on each metallic NP. Hence, it is perfectly
reasonable to doubt the truth of the result of SM-SERS
based on ultralow concentration, for it is possible that the
signals come from NPs that accumulate more molecules.
Following that, Aroca et al.(180) pointed out the
Langmuir–Blodgett technique to study SM-SERS. This
experiment is accomplished by reducing the concentra-
tion of target analyte in a spectrally ‘inert’ matrix (a
Raman SERS
Poor Excellent
Many molecules Single molecule
Excellent Excellent
10−4 eV 10−4 eV
Good Good
1 μm 1 μm
Excellent Excellent
10−9 s 10−9 s
No need Poor
Au, Ag, Cu
No need Poor nanostructures
Excellent Excellent
18
molecule with a very low Raman and SERS cross section
compared to the target analyte), typically a fatty acid
such as arachidic acid. The use of monomolecular films
reduces the probe volume to a probe area, which greatly
reduces the ambiguity of analyte concentration. However,
it is still within the ultralow-concentration approach and
therefore susceptible to problems of poor statistics.
To date, the single-molecule nature of SERS has
been completely proved through the bianalyte SERS
approach.(181) Research studies use isotopologs of dye
molecules whose affinity toward the surface is compa-
rable, but the spectral position of Raman modes differs
significantly. Thus, the presence of just one isotopolog
within the SERS spectrum gives an indication about the
single-molecule SERS event. Besides, a statistical crite-
rion for evaluating the single-molecule character was
proposed to extend and complement the bianalyte SERS
technique. In case of very low concentration, SERS signals
at different positions appear with a certain frequency,
with intensities spanning a certain range. If the signals
are truly from single molecules, when the concentration
is doubled, one expects to observe the same distribution
of intensities but twice as often (frequency scaling). In
contrast, if signals at different points are produced by
more than one molecule, an increase of the molecular
concentration will influence the signal intensity, but not
the frequency (intensity scaling).
One of the (still) not fully resolved issues finding
in various SM-SERS experiments is fluctuations of the
signal, meaning changes in the frequency, bandwidth,
relative intensity and, sometimes, an ‘on-and-off’ signal
(blinking).(183) These variations can be seen under
constant illumination and collection as well as in variation
between different SM spectra collected for the same
system. Blinking in SERS may be related in, some
instances, to thermal diffusion of a single molecule in
and out of hot spots, where changes in position of a few
nanometers can make a huge difference to the SERS
intensity.(184)
Taking advantage of SM-SERS, we can measure optical
properties that are not affected by inhomogeneous
broadening. This is a fundamental aspect of Raman
spectroscopy that SM-SERS has been able to unveil,
as exemplified by the determination of the resonance
excitation spectrum of a single molecule performed by
van Duyne et al.(185) Last but not least, special spectral
properties of molecules can be observed with SM-
SERS. For example, natural isotopic substitutions can
be detected.(186) Although many of these are textbook-
like examples of spectroscopy with no immediate
application, they demonstrate the exquisite level of
sophistication that SM-SERS, as a tool, has reached.
Furthermore, there is hope that SM-SERS studies will
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RAMAN SPECTROSCOPY
eventually shed some light into subtle aspects of biological
processes.
Finally, the EM EF under SM-SERS conditions is
found to be at maximum 1011 .(187) Higher enhancements
factors are accompanied by ultrafast photobleaching of
the investigated dye molecules. The minimum EF for SM-
SERS is given in the literature as approximately between
seven and eight orders of magnitude.(146)
2.4.2 Offset the Weakness of Surface-enhanced Raman
Scattering: Expanding the Generality of
Surface-enhanced Raman Scattering
As aforementioned, the limitation of SERS majorly
comes from the key factors of SPR. The properties of
SPR and the EFs of SERS depend on the material,
size/shape, and/or the length of the gap of the substrates,
the excitation wavelength, and the dielectric constants of
the medium.
Over the last three decades, the strategy of ‘borrowing
SERS activity’, coating weak or non-SERS materials on
the surfaces of SERS-active materials, was developed.
By taking the advantage of the long-range extension
of EM field enhancement due to SPR, method of
‘borrowing’ SERS activity from the coinage metals can
be used to partially expand the material generality of
SERS and improve the sensitivity of surface Raman of
molecules adsorbed on these overlayered materials, such
as polymers, semiconductors, and TMs.
For example, various metals such as the group VIII-B
TMs could be coated on SERS-active NPs or surface
nanostructures as ultrathin shells (one to five atomic
layers).(188) The surface Raman of the adsorbed molecules
on the surfaces of the TM shell (Pt, Pd, Ni, etc.) can
be amplified by the long-range EM field based on the
excitation of SPR of the underlying coinage metal. The
ASEFs can reach up to 103 –104 , and are about one
order or more of magnitude larger than that obtained on
massive metal electrodes.(29,48,188)
However, there are several shortages remaining. As
aforementioned, SERS EFs depend on the thickness
of the isolated shells; thus, it is desirable to synthesize
core–shell NPs or nanostructured surfaces with ultrathin
shells. However, it is not easy to coat many other materials
(such as insulators, semiconductors, and biological
membranes) onto coinage metal with controllable shell
thickness.
Moreover, SERS substrates still have bifunctional
roles; they act as amplifier of Raman signals and
supporter for the analyte molecules. This will lead to
several limitations. The first limitation is in morphology
generality; SERS substrates in contact mode still should
be nanostructured, which limits the contact-mode SERS
to be applied for routine detection on single-crystal
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
surfaces, which do not support SPR. Secondly, the
contact-mode SERS limits its application for heteroge-
neous catalytic science. As aforementioned, SERS signals
dominantly come from molecules in SERS hot spots,
whereas the reactive active sites may be not in the regime
of SERS hot spots.(189) This mismatch in SERS hot spots
and reaction-active sites may mislead us to understand
the detailed catalytic mechanisms. Therefore, it is very
desirable to develop a technique with controllable and
well-defined SERS hot spots, which is TERS.
3 TIP-ENHANCED RAMAN
SPECTROSCOPY
TERS as one of the variants of SERS combines
scanning probe microscopy (SPM) and Raman spec-
troscopy to simultaneously give us morphologic and
chemical information of the sample. Three indepen-
dent research groups, Zenobi,(190) Anderson,(191) and
Kawata,(192) invented TERS in 2000 based on the
atomic force microscope (AFM). Zenobi and Kawata
groups employed Ag-film-coated AFM tip as TERS tip,
whereas Anderson group used Au-film-coated AFM tip.
Pettinger’s group further developed a scanning tunneling
microscope (STM) based TERS by making use of EM
coupling between electrochemical etched silver tip with
Au film surfaces, which was later termed the gap-mode
TERS.(193)
3.1 Principles of Tip-enhanced Raman Spectroscopy
TERS uses the tips of AFM, STM, or shearing force
microscopy (SFM) as an amplifier of the Raman signals
(Figure 8d). The pure Ag or Au or their coated AFM tip
acts as an antenna for both incident and Raman fields.
Firstly, the incident field excites the localized surface
plasmon of the metallic tip that leads to a highly localized
optical field, as shown in Figure 11. Then, the molecules
underneath the tip will interact with the enhanced and
localized fields and irradiates Raman photons, and finally
the tip will further help the molecules to transmit the
Raman photons from the near field to far field to be
collected and detected by Raman systems. In addition to
SPR effect, lightning rod effect due to the sharp metallic
tip(194) may also contribute to the giant enhancement in
TERS. Because of the localization of the optical field and
the fact that the tip serves as the only controllable hot
spot, TERS can also provide a high spatial resolution by
performing chemical imaging.
When the substrate becomes a metallic surface,(193,196)
the optical response is similar to the EM coupling between
an NP dimer or between an NP and a plane metal surface.
The most enhanced field appears at the junction of the tip
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19
Ag/Au
SPM
E Tip
Raman
photons
Laser k
~1 nm
Sample
(a)
Tip
λ = 633 nm
10 nm
Enhancement factors
on the surface:
(b) 1011 109 107 103
Figure 11 (a) The schematic diagram showing the principle
of the TERS.(195) (b) TERS EF in the |E|4 approximation for a
gold tip on top of a gold surface. The tip is separated by a 2 nm
gap from the surface (in air). (Reproduced with permission from
Ref. 146. Copyright 2008, Royal Society of Chemistry.
and substrate. This gap-mode TERS can provide much
stronger signal compared with the normal TERS and
has been successfully applied for the study of monolayer
nonresonant molecule on single-crystal surfaces.(197,198)
The EF of this gap-mode TERS is so high that it
can even realize a single-molecule detection limit for
some resonant molecules.(187,196,198 – 200) This effect is not
just limited to Ag/Au surfaces, but also exists in other
metals, such as Ni, Al, Mo, W, and Pt. Moreover, because
of the strong EM coupling between Au tip and the
metal surfaces, the optical field distribution will be more
localized. In principle, the gap-mode TERS can provide
larger EF and higher spatial resolution than other types
of TERS.
In TERS, the SPM tip, in principle, does not need
to be in direct contact with the molecules adsorbed
on surfaces, and the tip serves only as the enhancer
and the sample is on the substrate. This feature is
much advantageous over SERS in terms of more
freedom of control because the SERS substrate serves
as both the signal amplifier and molecular supporter.
The high sensitivity, the high spatial resolution, and
better controllability make TERS a powerful tool
for the simultaneous and correlated spectroscopic and
20 RAMAN SPECTROSCOPY

morphologic characterizations of molecules adsorbed on
more general surfaces, such as smooth surfaces, single-
crystal surfaces, and cellular surfaces.
3.2 Preparation of the Tip-enhanced Raman
Spectroscopy Tip
In TERS, the tip mainly provides the EM enhancement.
Thus, a metallic tip with suitable optical and chemical
properties is vitally important for TERS. In our opinion,
there are four very basic requirements for a TERS tip: (i)
a sharp tip apex for SPM measurement to obtain high-
quality morphological image of the sample; (ii) ideal size
and shape for producing prominent field enhancement;
(iii) a smooth surface at the illuminated area of the
tip to exclude the contribution of SERS; and (iv) free
of contamination to suppress any possible background
signal.
3.3 Tip-enhanced Raman Spectroscopy Experiments
3.3.1 Tip-enhanced Raman Spectroscopy Setup
According to the differences in illumination and detection
geometry, there are three types of TERS instruments,
bottom illumination, side illumination, and top illumi-
nation either using microscope objective or parabolic
mirror. Each geometry has its advantages and disad-
vantages (Figure 12). For instance, bottom-illumination
TERS supports a high-numerical aperture (NA) objec-
tive with NA ≈ 1.4 to provide a tight focus, a high
collection efficiency of TERS signals, and a low back-
ground area. However, the bottom-illumination TERS
only works for transparent samples. On the contrary, the
side-illumination TERS can work for both the opaque
and transparent samples. However, the objective should
be arranged in a distant place, so that the NA of the objec-
tives usually should be smaller than 0.55. To compensate
this decrease in both excitation and collection efficiency,
usually a more intense laser or a gap-mode TERS
should be introduced. Top-illumination setup illuminates
light directly perpendicular to the sample surfaces and
combines the advantages of the high NA of the bottom-
illumination setup and the advantages of working on
nontransparent samples for the side-illumination setup.
For the objective types, the tip is located between the laser
focus and the objectives; some incident- and Raman-
scattered photons will be blocked by the tip and most
commonly used NA is below 0.7. This limitation can be
partially overcome using parabolic mirror, and an NA of
nearly 1.0 can be achieved.
3.3.2 Calculation of the Enhancement Factor of
Tip-enhanced Raman Spectroscopy
Several methods can be used to estimate the EFs. The
most simple approach is to calculate the contribution
of each molecule to the total Raman signal, taking into
account the different effective areas in two techniques
according to the following relation.(202)
(ITERS /NTERS ) (I /r2 )
G= ≈ TERS 2 TERS
(ISRR /NSRR ) (ISRR /r SRR )

Bottom-illumination Side-illumination where ITERS is the detected TERS in gap-mode TERS,

setup setup and the contribution of normal Raman signal to the
e
ctiv

detected TERS signal can be neglected. ISRR is the

je
Ob

Tip
surface resonance Raman (SRR) intensity of monolayer
Sample
adsorbed species. The most ambiguous factor influencing
Substrate the evaluation of TERS EFs is the estimation of the
Objective
(a) (b) number of molecules, NTERS in TERS, and NSRR in SRR,
which approximately can be the radii of laser spot and tip
apex, respectively.
Objective
Several experimental results and theoretical calcula-
tions have shown that the enhanced field will be localized
to a region equal to or smaller than the size of the tip
apex. Therefore, if we consider that the tip radius is about
Parabolic mirror Top-illumination 20 nm in the TERS measurement and the radius of the
setup setup laser spot is about 1000 nm in the SRR measurement, and
(c) (d)
that the SRR signal is about 1.3 cps and the TERS signal
is over 1600 cps with this specific tip, the G can be about
Figure 12 Illustration of the different TERS geometries:
(a) bottom illumination; (b) side illumination; (c) bottom 3 × 106 . This enhancement is comparable to that of SERS,
illustration using parabolic mirror; and (d) tip illumination. but produces a weaker signal because of the much lower
(Reproduced with permission from Ref. 201. Copyright 2012, amount of molecules measured by TERS. Moreover, such
Royal Society of Chemistry.) a high enhancement can only be achieved with a proper

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SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION 21

selection of the tip and the substrate, e.g. Au tip and Au
substrate in the present case.
The second approach to estimate the G value in TERS
is based on the measurement of time constant of the
photobleaching process of a dye molecule, as described
in Ref. 203.
3.4 Applications of Tip-enhanced Raman Spectroscopy
Because of its high sensitivity and high spatial resolution,
TERS has been widely applied in nanoscience, surface
science, catalytically chemistry, biological systems, etc.
For instance, Pettinger and Ren reported the first TERS
of MGITC on Au(1 1 1), and then they further extended
the study to other single-crystal surfaces, including
Au(1 1 0), Pt(1 1 0), and nonresonant molecules.(204)
Pettinger extended TERS from the ambient condition to
UHV systems, and reported a convincing single-molecule
TERS of brilliant cresyl blue (BCB) on Au(1 1 1).(196) Ren
et al.(128) developed a fishing-mode TERS to simultane-
ously detect mutual-correlated molecular conductance
and Raman spectra of molecules trapped in the molecule
junction form by the STM Au tip and the Au substrate.
In addition, TERS has also been applied for nanoscale
chemical imaging,(205 – 207) monitoring the heteroge-
neous catalytic reactions and studying the biological
systems,(208) and so on. With the further development
of tip and instrumentation, TERS will be a promising
tool providing chemical information at a high spatial
resolution, down to several nanometers.
4 SHELL-ISOLATED
NANOPARTICLE-ENHANCED
RAMAN SPECTROSCOPY
4.1 Principles of Shell-isolated Nanoparticle-enhanced
Raman Spectroscopy
SHINERS is the newest member of the SERS family.
The idea is similar to TERS, in which the advantage
of the long-range EM field enhancement effect is taken
to overcome the problem of substrate and morphology
generalities.
Figure 13 compares different working modes of
SERS, TERS, and SHINERS. The first one is the
contact mode for which the analyzed molecules directly
adsorb on nanostructured SERS substrates, i.e. the bare
nanostructured coinage metals and those with ultrathin
shell of TMs; see Figure 13(a) and (b). TERS works
in a noncontact mode, in which analytes are separated
from the tip as the signal enhancer in a short distance;
see Figure 13(c). Recently, Tian and coworkers have
developed a new shell-isolated mode.(61) In a SHINERS
experiment, highly SERS-active NPs are coated with an
ultrathin shell and then spread over any surface to be
probed; see Figure 13(d).
In SHINERS, the probe/analyte molecule is located on
a bulk sample of the weakly enhancing or nonenhancing
material, and shell-isolated nanaparticles (SHINs) are
spread over the top to generate the strong EM field.
The isolating shell, which is made of a chemically
inert dielectric, helps to maintain spectral integrity by

(a) (b)
Contact mode Transition metal shell

Bare Au Np

Supp Supp
ort ort
Au core

(c) Noncontact mode (d) Shell-isolated mode

Silica or alumina shell

Au tip Probed
molecules

Any s Any s
ubstr ubstr
ate & ate &
morp morp
holog holog
y y Au core

Figure 13 The working principle of SHINERS in comparison with the other modes. Schematic illustration of the contact mode:
(a) bare Au NPs and (b) Au core–TM shell NPs adsorbed by probed molecules; noncontact mode; (c) TERS; shell-isolated mode;
and (d) SHINERS. (Reproduced with permission from Ref. 61. Copyright 2010, Nature.)

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22
preventing direct contact between the core and the
system under study. In other words, the core may
be considered a contaminant and the shell keeps it
from interacting chemically or electrically with any
component of the system under study, thereby mitigating
the risk of interference. Then, the weakly enhancing or
nonenhancing materials that can be examined by SERS
are not limited to those that can be coated onto a coinage
metal NP in the form of an ultrathin shell.
In TERS, there is only a single hot-spot-supporting-
enhanced Raman, whereas in SHINERS, there are
thousands of hot spots that can be considered thousands
of hot spots from TERS tips. Thus, the EF of SHINERS
is typically two or three orders larger than that of TERS.
Besides its very high sensitivity, SHINERS works for
surfaces with all kinds of materials and morphologies,
and can effectively expand the generality of SERS.
The ultrathin dielectric shell, on the one side, prevents
the core from interacting with (i.e. contaminating) the
system under study, and, on the other side, can still
support the long-range EM tail provided by the plasmonic
Au/Ag core. The detailed procedures of the synthesis of
NPs with coinage-metal core and ultrathin chemically
inert overlayer (SiO2 , Al2 O3 , MnO2 , etc.) can be found
in Refs 61 and 209 In practice, the operation procedure
of SHINERS is simple. One only needs to spread the
SHINs on the surfaces of samples before making a Raman
detection.
4.2 The Generality of Shell-isolated
Nanoparticle-enhanced Raman Spectroscopy
Regarding the morphology generality, TERS and Otto-
mode-ATR coupled Raman spectroscopy (ATR-Raman)
can be used to obtain the surface Raman spectra from
single-crystal surfaces. However, there are some disad-
vantages when TERS is applied to liquid–solid interfaces.
Firstly, molecules in solution will adsorb on SPM tip and
contaminate the tip, which results in dominant Raman
signals from the contaminants. Secondly, it will be very
hard to confine the laser focus on the tip because of the
unavoidable refraction effect in air–liquid interfaces.
On the contrary, the isolated and chemically inert shells
in SHINs can prevent molecules from directly contacting
the surfaces of the metallic core. Therefore, SHINERS
can offset some disadvantages of TERS, and can be widely
applied for single-crystal surfaces of various materials
even in complex environments.
4.3 Reliability of Shell-isolated Nanoparticle-enhanced
Raman Spectroscopy
In analytical science, there are several factors related
to reliability, e.g. reproducibility, stability, cost-
effectiveness, and easy handling feature, which are
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DOI: 10.1002/9780470027318.a9276
RAMAN SPECTROSCOPY
essentially important to push the technique into practical
application and even market.
Generally, the spot-to-spot and substrate-to-substrate
reproducibilities of SERS activity are poor.(49) The
tremendous efforts have been made on the well-defined
NPs and nanostructured patterns to significantly improve
the reproducibility. However, even for the well-assembled
bare Ag/Au NPs arrays, the laser-induced fusion of
neighboring NPs may alter the structure of hot spots.
As the coinage metals (i.e. Au, Ag, and Cu) have quite
low cohesive energies, when laser irradiates the substrate,
surface atoms move around with more kinetic energy,
and SERS intensity is changeable as the nanostructure
deteriorates.
Natan(169) pointed out that there is a SERS uncertainty
Resolution # × reproducibility = constant
where ‘Resolution #’ denotes the degree of structural
precision/accuracy with the SERS-active surface. This
description can be extended to another form as follows:
Sensitivity × reproducibility = constant
Therefore, it is necessary to make a balance
between reasonable sensitivity and good reproducibility.
SHINERS offers a solution to this problem because the
shell can hold surface diffusion of atoms and prevent the
degradation of precisely fabricated metal nanostructures.
Regarding the stability, bare Au NPs in solutions
suffer from aggregation. The aging problem leads to
the stability and the reproducibility problems in practical
application, whereas the SHINs in solution are very stable
and maintain a reproducible enhanced Raman signal even
for five days, as shown in Figure 14.
There has been a growing emphasis on the detection
and in-depth characterization of analytes by SHINERS
for examining the surface of the skin, cells, and tissues
after biopsy(47) or surface chemistry of different molecules
on atomically flat or highly roughened surfaces of a
wide variety of materials through detailed examination of
their Raman spectra.(210,211) Examples could include the
probing of surface processes associated with corrosion
and catalysis.
In Table 2, we group currently three members of the
SERS family based on seven factors, namely, sensitivity,
spatial resolution, energetic resolution, time resolution
material generality, molecular generality and reliability.
They are judged on a three-point scale as poor, good, or
excellent.
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION 23

SHINERS 10 000 cps

Au 20 000 cps
Pyridine [0.01 M]
Pyridine [0.01 M]
>5 days >5 days

RSD = 27.9% RSD = 4.1%

800 900 1000 1100 1200 1300 800 900 1000 1100 1200 1300
(a) Wavenumber / cm−1 (b) Wavenumber / cm−1
Pyridine [0.01 M]

SHINERS
Au

0S 10S 30S 90S >5 d 0S 10S 30S 90S >5 d

(c) (d)

Figure 14 The stability of bare Au NPS and shell-isolated NPs.

Table 2 Comparison of SERS, TERS, and SHINERS in the viewpoints of analytical chemistry
SERS TERS SHINERS
(SPR + Raman) (SERS + SPM) (Many TERS)
Sensitivity Excellent Good Good
Single molecule Single molecule* Submonolayer
Energetic resolution Excellent Excellent Excellent
10−4 eV 10−4 eV 10−4 eV
Spatial resolution Good Excellent Good
∼1 μm ∼10 nm ∼1 μm
Time resolution Excellent Poor Excellent
10−9 s 0.1 s 10−9 s
Material generality Poor Good Excellent
Au, Ag, Cu Any substrate Any substrate
Molecular generality Excellent Poor Good
Reliability Poor Good Excellent
* TERS with single-molecule sensitivity can only be achieved for molecules with very large Raman scattering cross sections

especially those with resonance Raman effect.

4.4 Flexibility of Shell-isolated Nanoparticle-enhanced
Raman Spectroscopy
Conceptually, the strategy of SHINERS is completely
different from that of the other core–shell struc-
tures or overlayered structures that have been used
for various purposes very successfully, i.e. the Au-
core–silica-shell SERS marker (Figure 15a),(170,212)
atomic layer deposition (ALD) alumina-modified
AgFON (Figure 15b),(27,213) silica-core–Au-shell
(Figure 15d),(141) and Au-core–transition-metal-shell
NPs (Figure 15c).(48,214) The Raman signal detected with
SHINERS is from the target (probe) molecules adsorbed
on the smooth or atomically flat single-crystal surface
underneath Au@SiO2 NPs, see Figure 15(e), or from the
surface components of living cells or other materials.
The key advantage of SHINERS is the flexibility
as SHINs’ shell is defunctionalized and chemically
inert, simply acting as a spacer and isolator. This
makes SHINERS unprecedentedly applicable for diverse
samples and molecules with the large flexibility. All

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24 RAMAN SPECTROSCOPY

(a) Raman marker Au Ag

Polystyrene nanosphere Silica
Alumina films Probe molecules
Catalyst (d) Transition metal
(b) (c)
Au NP Au (e)
Ag

Au NP Au NP

Substrate Glass Substrate Substrate Any substrate

Figure 15 Schematic illustration of five core–shell NPs with different strategies: (a) Au NP coated with thick silica shell with the
Raman marker adsorbed directly on the core surface and the inert shell modified with a functional group (in blue) that can bind to the
target molecules (in orange). (b) ALD alumina-modified AgFON substrates stabilize the SERS activity of the underlying silver and
detect the analyte adsorbed on the alumina layer. (c) Au-core–TM-shell NP. (d) Silica-core–Au-shell NP. (e) Au-core–inert-shell
NP.

the other core–shell or overlayered structures have
to carefully design and fabricate the ultrathin shell
and overlayer of certain materials, which is extremely
difficult for semiconductors, polymers, and catalysts. For
SHINERS, one only needs to find a way to coat a limited
number of materials (such as SiO2 or Al2 O3 ) over Au or
Ag NPs as the isolated shell, then SHINs can be easily
spread over thousands of different materials (substrates)
to be studied.
5 OUTLOOK AND SUMMARY
After about four decades, SERS has been developed into
a powerful and versatile analytical tool, which provides
good reason for persisting extensive interest in this field.
Several approaches could be made to further improve
the sensitivity, resolution, generality, and reliability in the
near future as follows.
New plasmonic materials are very promising for the
SERS application in different wavelength regimes.(139)
The success of SERS depends on the development of
coinage nanostructured substrates in visible and near-
IR regimes. However, there are very few works on the
material development for UV-SERS reported.(59,215 – 217)
Very recently, Gray et al.(218) predicted that in addition
to the typical materials (e.g. Al and Rh), Ga, In, Sn, Tl,
Pb, and Bi can work for UV-SERS.
Regarding the new SERS substrates for the highest
sensitivity, Van Duyne has pointed out the concept of
‘density of hot spot’.(27) AgFON can provide ‘hot line’ for
SERS and lead to a high-average SERS EFs. It is highly
desirable to rationally design and develop new SERS
substrates with high density of hot spots. Moreover, it
is of interest to fabricate substrates supporting double
resonance in visible and/or near-IR that can provide
addition enhancement.(140)
For TERS or other SERS studies on single hot
spot, one should develop new nanostructures with the
maximal local EM field. Some novel substrates supporting
nanoresonance(219) will be very useful to enhance the
strength of the local sensitivity. One could adopt new
methods and techniques, such as directional antenna.(220)
Novel SPM tips such as a tip body coupled with grating(221)
or with NPs could support remote detection from the
tip.(222)
For analyzing the very complex samples, it could be
necessary for SERS as well as TERS and SHINERS
to be implemented with ultrafast spectroscopies, such
as femtosecond stimulated Raman spectroscopy to
improve the temporal resolution.(223) SERS can be
hyphenated with other techniques, especially separation
techniques, such as microfluidics(224,225) or fluorescence
spectroscopy.(226)
In the aspect of spatial resolution, very recently Kawata
et al.(227) developed a novel strategy for AFM–TERS by
eliminating the background signal from Raman image,
which can reach a 4-nm resolution. Some efforts in this
direction and/or by remote excitation can further provide
higher spatial resolution.(222)
In addition to SE-IRAS(37,228,229) and surface-
enhanced fluorescence spectroscopy, surface-enhanced
hyper-Raman spectroscopy (SE-HRS),(230,231) , surface-
enhanced sum frequency generation (SE-SFG),(232)
and surface-enhanced coherent anti-Stokes Raman
spectroscopy (SE-CARS),(233) which are considered as
the family members of surface-enhanced optical spectro-
scopies, will also be one of the important instruments for
the analysis.
Development of new theories and simulations is
one of the most important directions in this field.
In spite of the fact that the simulation methods
for EM distribution have been well developed, few

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SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION 25

works focused on the arithmetic of functional-oriented SE-SFG Surface-Enhanced Sum Frequency

design of novel plasmonic nanostructures for SERS, Generation
TERS, and SHINERS. Recently, Sukharev et al.(233,234) SERRS Surface-Enhanced Resonance Raman
reported an optimal control approach based on multiple- Spectroscopy
parameter genetic algorithms for the design of plasmonic SERS Surface-Enhanced Raman Scattering
nanostructures with predetermined optical properties and SFM Shearing Force Microscopy
functionalities. SHIN Shell-Isolated Nanaparticle
Regarding the unified theory of SERS, Lombardi(235) SHINERS Shell-Isolated Nanoparticle-Enhanced
recently reported an updated version by considering Raman Spectroscopy
molecular discrete energy levels coupled with the SM-SERRS Single Molecule Surface-Enhanced
continuous levels from metals. Jensen et al.(236,237) Resonance Raman Spectroscopy
established a time-dependent Kohn–Sham frame by SM-SERS Single-Molecule Surface-Enhanced
introducing a potential term from transition dipoles of Raman Scattering
metals. The most challenging work along this direction SPM Scanning Probe Microscopy
is the unified theory of SERS with the same-level SPP Surface Plasmon Polariton
description involving surface plasmon, nanostructure, and SPR Surface Plasmon Resonance
molecule in one system. SRR Surface Resonance Raman
STM Scanning Tunneling Microscope
(TD)-DFT (Time-Dependent) Density-Functional
ACKNOWLEDGMENTS Theory
TERS Tip-Enhanced Raman Spectroscopy
This work has been made possible by the financial support TM Transition Metal
provided by the Ministry of Science and Technology of UHV Ultrahigh-Vacuum
China (2011YQ030124 and 2010IM040100). UV Ultraviolet

ABBREVIATIONS AND ACRONYMS

RELATED ARTICLES
AFM Atomic Force Microscope
ALD Atomic Layer Deposition
ASEF Averaged Surface Enhancement Factor Surfaces (Volume 10)
ATR Attenuated Total Reflection Infrared and Raman Spectroscopy in Analysis of Surfaces
BCB Brilliant Cresyl Blue Raman Spectroscopy (Volume 15)
CARS Coherent Anti-Stokes Raman Raman Spectroscopy: Introduction • Fourier Trans-
Spectroscopy form Raman Instrumentation • Raman Scattering,
CE Chemical Effect Fundamentals
EBL Electron Beam Lithography
EC-ORC Electrochemical Oxidation and Raman Spectroscopy
Reduction Cycle Raman Spectroscopy of Catalysts
EF Enhancement Factor
EM Electromagnetic
IR Infrared REFERENCES
LSPR Localized Surface Plasmon Resonance
NA Numerical Aperture 1. C.V. Raman, K.S. Krishnan, ‘A New Type of Secondary
Radiation’, Nature, 121, 501–502 (1928).
NMR Nuclear Magnetic Resonance
NP Nanoparticle 2. E. Smith, G. Dent, Modern Raman Spectroscopy: A
RRS Resonance Raman Scattering Practical Approach, 1st edition, Wiley, Berlin, 2005.
S/N (Signal-to-Noise) Ratio 3. R.L. McCreery, Raman Spectroscopy for Chemical
SE-CARS Surface-Enhanced Coherent Anti-Stokes Analysis, 1st edition, John Wiley & Sons, Inc., Berlin,
Raman Spectroscopy 2000.
SE-HRS Surface-Enhanced Hyper-Raman 4. R. Hochleitner, N. Tarcea, G. Simon, W. Kiefer, J.
Spectroscopy Popp, ‘Micro-Raman Spectroscopy: A Valuable Tool for
SE-IRAS Surface-Enhanced Infrared Absorption the Investigation of Extraterrestrial Material’, J. Raman
Spectroscopy Spectrosc., 35, 515–518 (2004).

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This article is © 2013 John Wiley & Sons, Ltd.
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DOI: 10.1002/9780470027318.a9276
26
5. L.P. Choo-Smith, H.G. Edwards, H.P. Endtz, J.M. Kros,
F. Heule, H. Barr, J.S. Robinson Jr, H.A. Bruining, G.J.
Puppels, ‘Medical Applications of Raman Spectroscopy:
From Proof of Principle to Clinical Implementation’,
Biopolymers, 67, 1–9 (2002).
6. A.E. Grow, L.L. Wood, J.L. Claycomb, P.A. Thompson,
‘New Biochip Technology for Label-Free Detection of
Pathogens and Their Toxins’, J. Microbiol. Methods, 53,
221–233 (2003).
7. G.H. Thomas, ‘Modern Applications of Analytical Ultra-
centrifugation’, Annu. Rev. Biophys. Biomol. Struct., 28,
75 –100 (1999).
8. B.S. Galabov, T. Dudev, ‘Vibrational Intensities’, in
Vibrational Spectra and Structure, 1st edition, eds S.G.
Boris, D. Todor, Elsevier, Amsterdam, 189–214, Vol. 22,
1996.
9. M. Fleischmann, P.J. Hendra, A.J. McQuillan, ‘Raman
Spectra from Electrode Surfaces’, J. Chem. Soc. Chem.
Commun., 2, 80–81 (1973).
10. M. Fleischmann, P.J. Hendra, A.J. McQuillan, ‘Raman
Spectra of Pyridine Adsorbed at a Silver Electrode’,
Chem. Phys. Lett., 26, 163–166 (1974).
11. D.L. Jeanmaire, R.P. Van Duyne, ‘Surface Raman
Spectroelectrochemistry: Part I. Heterocyclic, Aromatic,
and Aliphatic Amines Adsorbed on the Anodized Silver
Electrode’, J. Electroanal. Chem., 84, 1–20 (1977).
12. M.G. Albrecht, J.A. Creighton, ‘Anomalously Intense
Raman Spectra of Pyridine at a Silver Electrode’, J. Am.
Chem. Soc., 99, 5215–5217 (1977).
13. R.K. Chang, T.E. Furtak (eds), Surface Enhanced Raman
Scattering, 1st edition, Plenum Press, New York and
London, 1982.
14. B. Pettinger, ‘In situ Raman Spectroscopy at Metal Elec-
trodes’ in Adsorption of Molecules at Metal Electrodes,
1st edition, eds J. Lipkowski, P.N. Ross, VCH, New York,
285–346, 1992.
15. J. Lipkowski, L. Stolberg, ‘Molecular Adsorption at Gold
and Silver Electrodes’ in Adsorption of Molecules at Metal
Electrodes, 1st edition, eds J. Lipkowski, P.N. Ross, VCH,
New York, 171–238, 1992.
16. X. Qian, X.-H. Peng, D.O. Ansari, Q. Yin-Goen, G.Z.
Chen, D.M. Shin, L. Yang, A.N. Young, M.D. Wang,
S. Nie, ‘In Vivo Tumor Targeting and Spectroscopic
Detection with Surface-Enhanced Raman Nanoparticle
Tags’, Nat. Biotechnol., 26, 83–90 (2008).
17. W. Wang, C. Ruan, B. Gu, ‘Development of Gold–Silica
Composite Nanoparticle Substrates for Perchlorate
Detection by Surface-Enhanced Raman Spectroscopy’,
Anal. Chim. Acta, 567, 121–126 (2006).
18. G.A. Baker, D.S. Moore, ‘Progress in Plasmonic
Engineering of Surface-enhanced Raman-Scattering
Substrates Toward Ultra-Trace Analysis’, Anal. Bioanal.
Chem., 382, 1751–1770 (2005).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
RAMAN SPECTROSCOPY
19. M. Moskovits, ‘Surface-enhanced Spectroscopy’, Rev.
Mod. Phys., 57, 783 (1985).
20. A. Otto, I. Mrozek, H. Grabhorn, W. Akemann, ‘Surface-
enhanced Raman Scattering’, J. Phys.: Condens. Matter,
4, 1143–1212 (1992).
21. M. Fleischmann, I.R. Hill, in ‘Raman Spectroscopy’ in
Comprehensive Treatise of Electrochemistry, 1st edition,
eds R.E. White, J.O.M. Bockris, B. Conway, E. Yeager,
Plenum, New York, 373–432, Vol. 8, 1984.
22. H. Metiu, P. Das, ‘The Electromagnetic Theory of Surface
Enhanced Spectroscopy’, Annu. Rev. Phys. Chem., 35,
507–536 (1984).
23. A. Otto, ‘Electronic Scattering, Spin Effects, SERS
and Morphic Effects’, in Light Scattering in Solids IV,
1st edition, eds M. Cardona, G. Güntherodt, Springer,
Berlin/Heidelberg, 289–418, Vol. 54, 1984.
24. T. Vo-Dinh, ‘Surface-enhanced Raman Spectroscopy
Using Metallic Nanostructures’, Trends Anal. Chem., 17,
557–582 (1998).
25. A. Campion, P. Kambhampati, ‘Surface-enhanced
Raman Scattering’, Chem. Soc. Rev., 27, 241–250 (1998).
26. K. Kneipp, H. Kneipp, I. Itzkan, R.R. Dasari, M.S.
Feld, ‘Ultrasensitive Chemical Analysis by Raman
Spectroscopy’, Chem. Rev., 99, 2957–2976 (1999).
27. P.L. Stiles, J.A. Dieringer, N.C. Shah, R.P. Van Duyne,
‘Surface-enhanced Raman Spectroscopy’, Annu. Rev.
Anal. Chem., 1, 601–626 (2008).
28. X.M. Qian, S.M. Nie, ‘Single-molecule and Single-
Nanoparticle SERS: From Fundamental Mechanisms to
Biomedical Applications’, Chem. Soc. Rev., 37, 912–920
(2008).
29. Z.Q. Tian, B. Ren, D.Y. Wu, ‘Surface-enhanced Raman
Scattering: From Noble to Transition Metals and from
Rough Surfaces to Ordered Nanostructures’, J. Phys.
Chem. B, 106, 9463–9483 (2002).
30. M. Moskovits, ‘Surface-enhanced Raman Spectroscopy:
A Brief Retrospective’, J. Raman Spectrosc., 36, 485–496
(2005).
31. N.P.W. Pieczonka, R.F. Aroca, ‘Inherent Complexities of
Trace Detection by Surface-enhanced Raman Scattering’,
ChemPhysChem, 6, 2473–2484 (2005).
32. S.E.J. Bell, N.M.S. Sirimuthu, ‘Quantitative Surface-
enhanced Raman Spectroscopy’, Chem. Soc. Rev., 37,
1012–1024 (2008).
33. M.J. Banholzer, J.E. Millstone, L. Qin, C.A. Mirkin,
‘Rationally Designed Nanostructures for Surface-
enhanced Raman Spectroscopy’, Chem. Soc. Rev., 37,
885–897 (2008).
34. D. Graham, K. Faulds, ‘Quantitative SERRS for DNA
Sequence Analysis’, Chem. Soc. Rev., 37, 1042–1051
(2008).
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
35. M.D. Porter, R.J. Lipert, L.M. Siperko, G. Wang, R.
Narayanan, ‘SERS as a Bioassay Platform: Fundamen-
tals, Design, and Applications’, Chem. Soc. Rev., 37,
1001–1011 (2008).
36. W.E. Smith, ‘Practical Understanding and use of
Surface Enhanced Raman Scattering / Surface Enhanced
Resonance Raman Scattering in Chemical and Biological
Analysis’, Chem. Soc. Rev., 37, 955–964 (2008).
37. R. Aroca, Surface-Enhanced Vibrational Spectroscopy,
1st edition, John Wiley & Sons, Chichester, 2006.
38. E.C. Le Ru, P.G. Etchegoin, Principles of Surface-
Enhanced Raman Spectroscopy and Related Plasmonic
Effects, 1st edition, Elsevier, Amsterdam, 2009.
39. K. Kneipp, M. Moskovits, H. Kneipp (eds), Surface-
Enhanced Raman Scattering Physics and Applications,
1st edition, Springer-Verlag, Berlin, 2006.
40. S. Schlücker (ed), Surface-Enhanced Raman Spec-
troscopy, Analytical, Biophysical and Lift Science Appli-
cations, 1st edition, Wiley-VCH Verlag GmbH & Co.
KGaA, Berlin, 2010.
41. D. Graham, R. Goodacre (eds), ‘Chemical and Bioanalyt-
ical Applications of Surface Enhanced Raman Scattering
Spectroscopy’, Chem. Soc. Rev., 37(Special Issue), (2008).
42. J. Popp, T. Mayerhöfer (eds), ‘Surface-enhanced Raman
Spectroscopy’, Anal. Bioanal. Chem., 394(Special Issue),
(2009).
43. R.J.C. Brown, L.F. Cohen, M.J.T. Milton (eds),
‘Surface enhanced Raman Spectroscopy’, Farady Discuss.,
132(Special Issue), (2006).
44. P.G. Etchegoin (ed), ‘Plasmonics and Spectroscopy’,
Phys. Chem. Chem. Phys., 15(Special Issue), (2013).
45. P. Etchegoin (ed), ‘New Frontiers in Surface-enhanced
Raman Scattering’, Phys. Chem. Chem., 11(Special Issue),
The Royal Society of Chemistry, (2009).
46. Z.Q. Tian (ed), ‘Surface-enhanced Raman Spectroscopy’,
J. Raman Spectrosc., 36(Special Issue), (2005).
47. J.R. Anema, J.F. Li, Z.L. Yang, B. Ren, Z.Q. Tian, ‘Shell-
Isolated Nanoparticle-Enhanced Raman Spectroscopy:
Expanding the Versatility of Surface-Enhanced Raman
Scattering’, Annu. Rev. Anal. Chem., 4, 129–150 (2011).
48. Z.Q. Tian, B. Ren, J.F. Li, Z.L. Yang, ‘Expanding Gener-
ality of Surface-enhanced Raman Spectroscopy with
Borrowing SERS Activity Strategy’, Chem. Commun.,
17, 3514–3534 (2007).
49. M.J. Natan, ‘Concluding Remarks Surface Enhanced
Raman Scattering’, Faraday Discuss., 132, 321–328
(2006).
50. B. Pettinger, U. Wenning, H. Wetzel, ‘Surface Plasmon
Enhanced Raman Scattering Frequency and Angular
Resonance of Raman Scattered Light from Pyridine on
Au, Ag and Cu Electrodes’, Surf. Sci., 101, 409–416
(1980).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
27
51. J.A. Creighton, C.G. Blatchford, M.G. Albrecht, ‘Plasma
Resonance Enhancement of Raman Scattering by
Pyridine Adsorbed on Silver or Gold Sol Particles of
Size Comparable to the Excitation Wavelength’, J. Chem.
Soc., Faraday Trans. 2, 75, 790–798 (1979).
52. Y.J. Chen, W.P. Chen, E. Burstein, ‘Surface-
Electromagnetic-Wave-enhanced Raman Scattering
by Overlayers on Metals’, Phys. Rev. Lett., 36, 1207–1210
(1976).
53. P.H. McBreen, M. Moskovits, ‘Optical Properties of
Silver Films Deposited at Low Temperatures’, J. Appl.
Phys., 54, 329–335 (1983).
54. K. Carron, K. Mullen, M. Lanouette, H. Angersbach,
‘Selective-Ultratrace Detection of Metal Ions with
SERS.Pdf’, Appl. Spectrosc., 45, 420 (1991).
55. J.C. Rubim, ‘Surface-enhanced Raman Scattering
(SERS) on Silver Electrodes as a Technical Tool in the
Study of the Electrochemical Reduction of Cyanopy-
ridines and in Quantitative Analysis’, J. Electroanal.
Chem., 220, 339–350 (1987).
56. R. Sheng, F. Ni, T.M. Cotton, ‘Determination of Purine
Bases by Reversed-Phase High-performance Liquid
Chromatography Using Real-time Surface-enhanced
Raman Spectroscopy’, Anal. Chem., 63, 437–442 (1991).
57. S. Nie, S.R. Emory, ‘Probing Single Molecules and Single
Nanoparticles by Surface-enhanced Raman Scattering’,
Science, 275, 1102–1106 (1997).
58. K. Kneipp, Y. Wang, H. Kneipp, L.T. Perelman, I. Itzkan,
R.R. Dasari, M.S. Feld, ‘Single Molecule Detection Using
Surface-enhanced Raman Scattering (SERS)’, Phys. Rev.
Lett., 78, 1667–1670 (1997).
59. Z.Q. Tian, Z.L. Yang, B. Ren, D.Y. Wu, ‘SERS from
Transition Metals and Excited by Ultraviolet Light’
in Surface-enhanced Raman Scattering, 1st edition, eds
K. Kneipp, M. Moskovits, H. Kneipp, Springer, Berlin
Heidelberg, 125–146, 2006.
60. Z.Q. Tian, Z.L. Yang, B. Ren, J.F. Li, Y. Zhang, X.F. Lin,
J.-W. Hu, D.Y. Wu, ‘Surface-enhanced Raman Scattering
from Transition Metals with Special Surface Morphology
and Nanoparticle Shape’, Faraday Discuss., 132, 159–170
(2006).
61. J.F. Li, Y.F. Huang, Y. Ding, Z.L. Yang, S.B. Li, X.S.
Zhou, F.R. Fan, W. Zhang, Z.Y. Zhou, Y. WuDe, B.
Ren, Z.L. Wang, Z.Q. Tian, ‘Shell-isolated Nanoparticle-
enhanced Raman Spectroscopy’, Nature, 464, 392–395
(2010).
62. A.M. Michaels, M. Nirmal, L.E. Brus, ‘Surface Enhanced
Raman Spectroscopy of Individual Rhodamine 6G
Molecules on Large Ag Nanocrystals’, J. Am. Chem.
Soc., 121, 9932–9939 (1999).
63. H. Xu, E.J. Bjerneld, M. Käll, L. Börjesson, ‘Spectroscopy
of Single Hemoglobin Molecules by Surface Enhanced
Raman Scattering’, Phys. Rev. Lett., 83, 4357 (1999).
28
64. H. Xu, J. Aizpurua, M. Käll, P. Apell, ‘Electromagnetic
Contributions to Single-Molecule Sensitivity in Surface-
enhanced Raman Scattering’, Phys. Rev. E, 62, 4318–4324
(2000).
65. J.A. Dieringer, R.B. Lettan, K.A. Scheidt, R.P. Van
Duyne, ‘A Frequency Domain Existence Proof of Single-
Molecule Surface-enhanced Raman Spectroscopy’, J.
Am. Chem. Soc., 129, 16249–16256 (2007).
66. T.E. Furtak, J. Reyes, ‘A Critical Analysis of Theoretical
Models for the Giant Raman Effect from Adsorbed
Molecules’, Surf. Sci., 93, 351–382 (1980).
67. T.E. Furtak, ‘Current Understanding of the Mechanism
of Surface Enhanced Raman Scattering’, J. Electroanal.
Chem., 150, 375–388 (1983).
68. G.C. Schatz, ‘Theoretical Studies of Surface Enhanced
Raman Scattering’, Acc. Chem. Res., 17, 370–376 (1984).
69. G. Schatz, M. Young, R. Van Duyne, ‘Electromagnetic
mechanism of SERS’ in Surface-enhanced Raman Scat-
tering, 1st edition, eds K. Kneipp, M. Moskovits, H.
Kneipp, Springer, Berlin Heidelberg, 19–45, 2006.
70. J.I. Gersten, R.L. Birke, J.R. Lombardi, ‘Theory of
Enhanced Light Scattering from Molecules Adsorbed
at the Metal-Solution Interface’, Phys. Rev. Lett., 43, 147
(1979).
71. J.R. Lombardi, R.L. Birke, T. Lu, J. Xu, ‘Charge-transfer
Theory of Surface Enhanced Raman Spectroscopy:
Herzberg–Teller Contributions’, J. Chem. Phys., 84,
4174–4180 (1986).
72. A. Campion, ‘Raman Spectroscopy of Molecules
Adsorbed on Solid Surfaces’, Annu. Rev. Phys. Chem.,
36, 549–572 (1985).
73. L. Jensen, C.M. Aikens, G.C. Schatz, ‘Electronic Struc-
ture Methods for Studying Surface-enhanced Raman
Scattering’, Chem. Soc. Rev., 37, 1061–1073 (2008).
74. A. Otto, ‘The ’Chemical’ (Electronic) Contribution
to Surface-enhanced Raman Scattering’, J. Raman
Spectrosc., 36, 497–509 (2005).
75. X.M. Lin, Y. Cui, Y.H. Xu, B. Ren, Z.Q. Tian,
‘Surface-enhanced Raman Spectroscopy: Substrate-
related Issues’, Anal. Bioanal. Chem., 394, 1729–1745
(2009).
76. R.H. Ritchie, ‘Plasma Losses by Fast Electrons in Thin
Films’, Phys. Rev., 106, 874 (1957).
77. S. Maier, Plasmonics: Fundamentals and Applications, 1st
edition, Springer, New York, 2007.
78. K.M. Kosuda, J.M. Bingham, K.L. Wustholz, R.P.
Van Duyne, ‘Nanostructures and Surface-Enhanced
Raman Spectroscopy’ in Comprehensive Nanoscience
and Technology, 1st edition, eds D.L. Andrews, G.S.
Scholes, G.P. Wiederrecht, Academic Press, Amsterdam,
263–301, 2011.
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
RAMAN SPECTROSCOPY
79. M. Moskovits, ‘Surface Roughness and the Enhanced
Intensity of Raman Scattering by Molecules Adsorbed
on Metals’, J. Chem. Phys., 69, 4159–4161 (1978).
80. R. Dornhaus, R.E. Benner, R.K. Chang, I. Chabay,
‘Surface Plasmon Contribution to SERS’, Surf. Sci., 101,
367–373 (1980).
81. P.W. Barber, R.K. Chang, H. Massoudi, ‘Surface-
enhanced Electric Intensities on Large Silver Spheroids’,
Phys. Rev. Lett., 50, 997 (1983).
82. J.I. Gersten, ‘The Effect of Surface Roughness on
Surface Enhanced Raman Scattering’, J. Chem. Phys.,
72, 5779–5780 (1980).
83. J.I. Gersten, ‘Rayleigh, Mie, and Raman Scattering by
Molecules Adsorbed on Rough Surfaces’, J. Chem. Phys.,
72, 5780–5781 (1980).
84. J. Gersten, A. Nitzan, ‘Electromagnetic Theory of
Enhanced Raman Scattering by Molecules Adsorbed on
Rough Surfaces’, J. Chem. Phys., 73, 3023–3037 (1980).
85. D.A. Weitz, S. Garoff, J.I. Gersten, A. Nitzan, ‘The
Enhancement of Raman Scattering, Resonance Raman
Scattering, and Fluorescence from Molecules Adsorbed
on a Rough Silver Surface’, J. Chem. Phys., 78, 5324–5338
(1983).
86. S.L. McCall, P.M. Platzman, ‘Raman Scattering from
Chemisorbed Molecules at Surfaces’, Phys. Rev. B, 22,
1660–1662 (1980).
87. S.L. McCall, P.M. Platzman, P.A. Wolff, ‘Surface
Enhanced Raman Scattering’, Phys. Lett. A, 77, 381–383
(1980).
88. M. Kerker, ‘Resonances in Electromagnetic Scattering
by Objects with Negative Absorption’, Appl. Opt., 18,
1180–1189 (1979).
89. M. Kerker, D.-S. Wang, H. Chew, ‘Surface Enhanced
Raman Scattering (SERS) by Molecules Adsorbed at
Spherical Particles: Errata’, Appl. Opt., 19, 4159–4174
(1980).
90. M. Kerker, ‘Electromagnetic Model for Surface-
enhanced Raman Scattering (SERS) on Metal Colloids’,
Acc. Chem. Res., 17, 271–277 (1984).
91. P.K. Aravind, A. Nitzan, H. Metiu, ‘The Interaction
Between Electromagnetic Resonances and its Role
in Spectroscopic Studies of Molecules Adsorbed on
Colloidal Particles or Metal Spheres’, Surf. Sci., 110,
189–204 (1981).
92. H. Metiu, ‘Surface Enhanced Spectroscopy’, Prog. Surf.
Sci., 17, 153–320 (1984).
93. U. Laor, G.C. Schatz, ‘The Role of Surface Roughness
in Surface Enhanced Raman Spectroscopy (SERS): The
Importance of Multiple Plasmon Resonances’, Chem.
Phys. Lett., 82, 566–570 (1981).
94. U. Laor, G.C. Schatz, ‘The Effect of Randomly
Distributed Surface Bumps on Local Field Enhancements
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
in Surface Enhanced Raman Spectroscopy’, J. Chem.
Phys., 76, 2888–2899 (1982).
95. M. Moskovits, J.E. Hulse, ‘The Ultraviolet-Visible
Spectra of Diatomic, Triatomic, and Higher Nickel
Clusters’, J. Chem. Phys., 66, 3988–3994 (1977).
96. J.A. Creighton, M.G. Albrecht, R.E. Hester, J.A.D.
Matthew, ‘The Dependence of the Intensity of Raman
Bands of Pyridine at a Silver Electrode on the Wavelength
of Excitation’, Chem. Phys. Lett., 55, 55–58 (1978).
97. M. Moskovits, J.S. Suh, ‘Surface Selection Rules for
Surface-enhanced Raman Spectroscopy: Calculations and
Application to the Surface-enhanced Raman Spectrum
of Phthalazine on Silver’, J. Phys. Chem., 88, 5526–5530
(1984).
98. C.G. Blatchford, J.R. Campbell, J.A. Creighton, ‘Plasma
Resonance - Enhanced Raman Scattering by Absorbates
on Gold Colloids: The Effects of Aggregation’, Surf. Sci.,
120, 435–455 (1982).
99. P.K. Aravind, H. Metiu, ‘The Effects of the Interaction
Between Resonances in the Electromagnetic Response
of a Sphere-Plane Structure; Applications to Surface
Enhanced Spectroscopy’, Surf. Sci., 124, 506–528 (1983).
100. T. Jensen, L. Kelly, A. Lazarides, G.C. Schatz, ‘Electro-
dynamics of Noble Metal Nanoparticles and Nanoparticle
Clusters’, J. Cluster Sci., 10, 295–317 (1999).
101. K.L. Kelly, E. Coronado, L.L. Zhao, G.C. Schatz, ‘The
Optical Properties of Metal Nanoparticles: The Influence
of Size, Shape, and Dielectric Environment’, J. Phys.
Chem. B, 107, 668–677 (2003).
102. H. Chew, P.J. McNulty, M. Kerker, ‘Model for Raman
and Fluorescent Scattering by Molecules Embedded in
Small Particles’, Phys. Rev. A, 13, 396–404 (1976).
103. J.C. Tsang, J.R. Kirtley, T.N. Theis, ‘Surface Plasmon
Polariton Contributions to Strokes Emission from
Molecular Monolayers on Periodic ag Surfaces’, Solid
State Commun., 35, 667–670 (1980).
104. B.N.J. Persson, ‘On the Theory of Surface-enhanced
Raman Scattering’, Chem. Phys. Lett., 82, 561–565 (1981).
105. A. Otto, J. Billmann, J. Eickmans, U. Ertürk, C.
Pettenkofer, ‘The ‘‘Adatom Model’’ of SERS (Surface
Enhanced Raman Scattering): The Present Status’, Surf.
Sci., 138, 319–338 (1984).
106. S. Efrima, H. Metiu, ‘Light Scattering by a Molecule Near
a Solid Surface. II. Model Calculations’, J. Chem. Phys.,
70, 2297–2309 (1979).
107. S. Efrima, H. Metiu, ‘Surface Induced Resonant Raman
Scattering (SIRRS)’, Surf. Sci., 92, 417–432 (1980).
108. H. Ueba, S. Ichimura, ‘Raman Scattering of Adsorbed
Molecules’, J. Chem. Phys., 74, 3070–3075 (1981).
109. H. Ueba, S. Ichimura, H. Yamada, ‘Where are We in
the Study of SERS? Role of Chemisorption and Charge
Transfer’, Surf. Sci., 119, 433–448 (1982).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
29
110. D. Roy, T.E. Furtak, ‘Evidence for Ag Cluster Vibrations
in Enhanced Raman Scattering from the Ag/Electrolyte
Interface’, Chem. Phys. Lett., 124, 299–303 (1986).
111. F.W. King, R.P. Van Duyne, G.C. Schatz, ‘Theory of
Raman Scattering by Molecules Adsorbed on Electrode
Surfaces’, J. Chem. Phys., 69, 4472–4481 (1978).
112. Z.Q. Tian, ‘General Discussion’, Faraday Discuss., 132,
309–319 (2006).
113. S. Y. Ding, ‘Plasmon-enhanced Vibrational Spectroscopy
and Raman Optical Activity: Theories, Methods and
Applications’. PhD Thesis, Department of Chemistry,
Xiamen University, Xiamen, (2012).
114. D. Roy, T.E. Furtak, ‘Characterization of Surface
Complexes in Enhanced Raman Scattering’, J. Chem.
Phys., 81, 4168–4175 (1984).
115. D.Y. Wu, B. Ren, Y.X. Jiang, X. Xu, Z.Q. Tian,
‘Density Functional Study and Normal-Mode Analysis
of the Bindings and Vibrational Frequency Shifts of the
Pyridine-M (M = Cu, Ag, Au, Cu+ , Ag+ , Au+ , and Pt)
Complexes’, J. Phys. Chem. A, 106, 9042–9052 (2002).
116. A. Vivoni, R.L. Birke, R. Foucault, J.R. Lombardi, ‘Ab
Initio Frequency Calculations of Pyridine Adsorbed on
an Adatom Model of a SERS Active Site of a Silver
Surface’, J. Phys. Chem. B, 107, 5547–5557 (2003).
117. S.Y. Ding, B.J. Liu, Q.N. Jiang, D.Y. Wu, B. Ren, X. Xu,
Z.Q. Tian, ‘Cations-Modified Cluster Model for Density-
Functional Theory Simulation of Potential Dependent
Raman Scattering from Surface Complex/Electrode
Systems’, Chem. Commun., 48, 4962–4964 (2012).
118. D.Y. Wu, M. Hayashi, S.H. Lin, Z.Q. Tian, ‘Theoretical
Differential Raman Scattering Cross-Sections of Totally-
Symmetric Vibrational Modes of Free Pyridine and
Pyridine-Metal Cluster Complexes’, Spectrochim. Acta,
Part A, 60, 137–146 (2004).
119. L.L. Zhao, L. Jensen, G.C. Schatz, ‘Pyridine-Ag20 Cluster:
A Model System for Studying Surface-enhanced Raman
Scattering’, J. Am. Chem. Soc., 128, 2911–2919 (2006).
120. D.Y. Wu, X.M. Liu, S. Duan, X. Xu, B. Ren, S.H. Lin, Z.Q.
Tian, ‘Chemical Enhancement Effects in SERS Spectra:
A Quantum Chemical Study of Pyridine Interacting with
Copper, Silver, Gold and Platinum Metals’, J. Phys.
Chem. C, 112, 4195–4204 (2008).
121. D.W. Silverstein, L. Jensen, ‘Vibronic Coupling Simu-
lations for Linear and Nonlinear Optical Processes:
Theory’, J. Chem. Phys., 136, 064111–064113 (2012).
122. J.R. Lombardi, R.L. Birke, ‘Time-Dependent Picture
of the Charge-Transfer Contributions to Surface
Enhanced Raman Spectroscopy’, J. Chem. Phys., 126,
244709–244709 (2007).
123. J.F. Arenas, I. LopezTocon, J.C. Otero, J.I. Marcos,
‘Charge Transfer Processes in Surface-enhanced Raman
Scattering. Franck-Condon Active Vibrations of Pyri-
dine’, J. Phys. Chem., 100, 9254–9261 (1996).
30
124. J.F. Arenas, J. Soto, I.L. Tocon, D.J. Fernandez, J.C.
Otero, J.I. Marcos, ‘The Role of Charge-Transfer States
of the Metal-Adsorbate Complex in Surface-enhanced
Raman Scattering’, J. Chem. Phys., 116, 7207–7216
(2002).
125. J.F. Li, Y.F. Huang, S. Duan, R. Pang, D.-Y. Wu, B. Ren,
X. Xu, Z.Q. Tian, ‘SERS and dft Study of Water on Metal
Cathodes of Silver, Gold and Platinum Nanoparticles’,
Phys. Chem. Chem. Phys., 12, 2493–2502 (2010).
126. H. Yui, ‘Electron-enhanced Raman Scattering: A History
of its Discovery and Spectroscopic Applications to
Solution and Interfacial Chemistry’, Anal. Bioanal.
Chem., 397, 1181–1190 (2010).
127. M. Galperin, M.A. Ratner, A. Nitzan, ‘Raman Scattering
in Current-Carrying Molecular Junctions’, J. Chem. Phys.,
130, 144109–144119 (2009).
128. Z. Liu, S.Y. Ding, Z.B. Chen, X. Wang, J.H. Tian, J.R.
Anema, X.S. Zhou, D.Y. Wu, B.W. Mao, X. Xu, B. Ren,
Z.Q. Tian, ‘Revealing the Molecular Structure of Single-
Molecule Junctions in Different Conductance States by
Fishing-Mode Tip-enhanced Raman Spectroscopy’, Nat.
Commun., 2, 305 (2011).
129. E.J. Zeman, G.C. Schatz, ‘An Accurate Electromagnetic
Theory Study of Surface Enhancement Factors for Silver,
Gold, Copper, Lithium, Sodium, Aluminum, Gallium,
Indium, Zinc, and Cadmium’, J. Phys. Chem., 91, 634–643
(1987).
130. J.A. Creighton, D.G. Eadon, ‘Ultraviolet-visible Absorp-
tion Spectra of the Colloidal Metallic Elements’, J. Chem.
Soc., Faraday Trans., 87, 3881–3891 (1991).
131. D. Pines, ‘Collective Energy Losses in Solids’, Rev. Mod.
Phys., 28, 184 (1956).
132. C.J. Powell, J.B. Swan, ‘Effect of Oxidation on the Char-
acteristic Loss Spectra of Aluminum and Magnesium’,
Phys. Rev., 118, 640 (1960).
133. E. Kretschmann, H. Raether, ‘Radiative Decay of Non-
radiative Surface Plasmons Excited by Light’, Z. Naturf.
A, 23, 2135–2136 (1968).
134. A. Otto, ‘Excitation of Nonradiative Surface Plasma
Waves in Silver by the Method of Frustrated Total
Reflection’, Z. für Phys. A, 216, 398–410 (1968).
135. R.H. Ritchie, E.T. Arakawa, J.J. Cowan, R.N. Hamm,
‘Surface-Plasmon Resonance Effect in Grating Diffrac-
tion’, Phys. Rev. Lett., 21, 1530 (1968).
136. U. Kreibig, P. Zacharias, ‘Surface Plasma Resonances in
Small Spherical Silver and Gold Particles’, Z. für Phys.
A, 231, 128–143 (1970).
137. K.I. Yoshida, T. Itoh, H. Tamaru, V. Biju, M. Ishikawa,
Y. Ozaki, ‘Quantitative Evaluation of Electromagnetic
Enhancement in Surface-enhanced Resonance Raman
Scattering from Plasmonic Properties and Morphologies
of Individual Ag Nanostructures’, Phys. Rev. B, 81, 115406
(2010).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
RAMAN SPECTROSCOPY
138. B. Sharma, R.R. Frontiera, A.-I. Henry, E. Ringe, R.P.
Van Duyne, ‘SERS: Materials, Applications, and the
Future’, Mater. Today, 15, 16–25 (2012).
139. A. Boltasseva, H.A. Atwater, ‘Low-loss Plasmonic
Metamaterials’, Science, 331, 290–291 (2011).
140. Y. Chu, D. Wang, W. Zhu, K.B. Crozier, ‘Double Reso-
nance Surface Enhanced Raman Scattering Substrates:
An Intuitive Coupled Oscillator Model’, Opt. Express,
19, 14919–14928 (2011).
141. S. Lal, N.K. Grady, J. Kundu, C.S. Levin, J.B. Lassiter,
N.J. Halas, ‘Tailoring Plasmonic Substrates for Surface
Enhanced Spectroscopies’, Chem. Soc. Rev., 37, 898–911
(2008).
142. S. Link, M.A. El-Sayed, ‘Spectral Properties and
Relaxation Dynamics of Surface Plasmon Electronic
Oscillations in Gold and Silver Nanodots and Nanorods’,
J. Phys. Chem. B, 103, 8410–8426 (1999).
143. S. Link, M.A. El-Sayed, ‘Shape and Size Dependence of
Radiative, Non-radiative and Photothermal Properties of
Gold Nanocrystals’, Int. Rev. Phys. Chem., 19, 409–453
(2000).
144. E.C. Le Ru, P.G. Etchegoin, ‘Single-Molecule Surface-
enhanced Raman Spectroscopy’, Annu. Rev. Phys. Chem.,
63, 65–87 (2012).
145. R. Boyack, E.C. Le Ru, ‘Investigation of Particle Shape
and Size Effects in SERS Using T-matrix Calculations’,
Phys. Chem. Chem. Phys., 11, 7398–7405 (2009).
146. P.G. Etchegoin, E.C. Le Ru, ‘A Perspective on Single
Molecule SERS: Current Status and Future Challenges’,
Phys. Chem. Chem. Phys., 10, 6079–6089 (2008).
147. J. Zuloaga, E. Prodan, P. Nordlander, ‘Quantum
Description of the Plasmon Resonances of a Nanoparticle
Dimer’, Nano Lett., 9, 887–891 (2009).
148. R. Esteban, A.G. Borisov, P. Nordlander, J. Aizpurua,
‘Bridging Quantum and Classical Plasmonics with a
Quantum-Corrected Model’, Nat. Commun., 3, 825
(2012).
149. H. Duan, A.I. Fernández-Domı́nguez, M. Bosman, S.A.
Maier, J.K.W. Yang, ‘Nanoplasmonics: Classical Down to
the Nanometer Scale’, Nano Lett., 12, 1683–1689 (2012).
150. T. Shegai, Z. Li, T. Dadosh, Z. Zhang, H. Xu, G. Haran,
‘Managing Light Polarization via Plasmon–Molecule
Interactions Within an Asymmetric Metal Nanoparticle
Trimer’, Proc. Natl. Acad. Sci. U. S. A., 105, 16448–16453
(2008).
151. C.E. Talley, J.B. Jackson, C. Oubre, N.K. Grady,
C.W. Hollars, S.M. Lane, T.R. Huser, P. Nordlander,
N.J. Halas, ‘Surface-enhanced Raman Scattering from
Individual Au Nanoparticles and Nanoparticle Dimer
Substrates’, Nano Lett., 5, 1569–1574 (2005).
152. K.L. Wustholz, A.-I. Henry, J.M. McMahon, R.G.
Freeman, N. Valley, M.E. Piotti, M.J. Natan, G.C.
Schatz, R.P.V. Duyne, ‘Structure−Activity Relationships
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
in Gold Nanoparticle Dimers and Trimers for Surface-
enhanced Raman Spectroscopy’, J. Am. Chem. Soc., 132,
10903–10910 (2010).
153. K.A. Willets, R.P. Van Duyne, ‘Localized Surface
Plasmon Resonance Spectroscopy and Sensing’, Annu.
Rev. Phys. Chem., 58, 267–297 (2007).
154. J.N. Anker, W.P. Hall, O. Lyandres, N.C. Shah, J.
Zhao, R.P. Van Duyne, ‘Biosensing with Plasmonic
Nanosensors’, Nat. Mater., 7, 442–453 (2008).
155. A.V. Zayats, I.I. Smolyaninov, A.A. Maradudin, ‘Nano-
Optics of Surface Plasmon Polaritons’, Phys. Rep., 408,
131–314 (2005).
156. W.L. Barnes, A. Dereux, T.W. Ebbesen, ‘Surface
Plasmon Subwavelength Optics’, Nature, 424, 824–830
(2003).
157. Z.Q. Tian, ‘Infrared and Raman Spectroscopy in Analysis
of Surfaces’, in Encyclopedia of Analytical Chemistry,
1st edition, ed. R. A. Meyers, John Wiley & Sons Ltd,
Chichester, 2000, 9162–9201.
158. Z. Wang, S. Pan, T.D. Krauss, H. Du, L.J. Rothberg,
‘The Structural Basis for Giant Enhancement Enabling
Single-Molecule Raman Scattering’, Proc. Natl. Acad. Sci.
U. S. A., 100, 8638–8643 (2003).
159. P.F. Liao, J.G. Bergman, D.S. Chemla, A. Wokaun, J.
Melngailis, A.M. Hawryluk, N.P. Economou, ‘Surface-
enhanced Raman Scattering from Microlithographic
Silver Particle Surfaces’, Chem. Phys. Lett., 82, 355–359
(1981).
160. D.R. Ward, N.K. Grady, C.S. Levin, N.J. Halas, Y. Wu,
P. Nordlander, D. Natelson, ‘Electromigrated Nanoscale
Gaps for Surface-enhanced Raman Spectroscopy’, Nano
Lett., 7, 1396 (2007).
161. N.A. Hatab, C.H. Hsueh, A.L. Gaddis, S.T. Retterer,
J.H. Li, G. Eres, Z. Zhang, B. Gu, ‘Free-standing
Optical Gold Bowtie Nanoantenna with Variable gap
Size for Enhanced Raman Spectroscopy’, Nano Lett., 10,
4952–4955 (2010).
162. D.A. Weitz, M. Oliveria, ‘Fractal Structures Formed by
Kinetic Aggregation of Aqueous Gold Colloids’, Phys.
Rev. Lett., 52, 1433–1436 (1984).
163. C.L. Haynes, R.P. Van Duyne, ‘Nanosphere Lithography:
A Versatile Nanofabrication Tool for Studies of Size-
dependent Nanoparticle Optics’, J. Phys. Chem. B, 105,
5599–5611 (2001).
164. W. Li, P.H.C. Camargo, X. Lu, Y. Xia, ‘Dimers of Silver
Nanospheres: Facile Synthesis and Their Use as Hot Spots
for Surface-enhanced Raman Scattering’, Nano Lett., 9,
485–490 (2009).
165. B. Ren, G.K. Liu, X.B. Lian, Z.L. Yang, Z.Q. Tian,
‘Raman Spectroscopy on Transition Metals’, Anal.
Bioanal. Chem., 388, 29–45 (2007).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
31
166. J. Eickmans, A. Otto, A. Goldmann, ‘On the Annealing
of ‘‘SERS Active’’ Silver Films: Ups and tds of Adsorbed
Xenon’, Surf. Sci., 171, 415–441 (1986).
167. M. Moskovits, ‘The Dependence of the Metal-Molecule
Vibrational Frequency on the Mass of the Adsorbate
and its Relevance to the Role of Adatoms in Surface-
enhanced Raman Scattering’, Chem. Phys. Lett., 98,
498–502 (1983).
168. J.E. Rowe, C.V. Shank, D.A. Zwemer, C.A. Murray,
‘Ultrahigh-Vacuum Studies of Enhanced Raman Scat-
tering from Pyridine on Ag Surfaces’, Phys. Rev. Lett., 44,
1770–1773 (1980).
169. R.G. Freeman, K.C. Grabar, K.J. Allison, R.M. Bright,
J.A. Davis, A.P. Guthrie, M.B. Hommer, M.A. Jackson,
P.C. Smith, D.G. Walter, M.J. Natan, ‘Self-assembled
Metal Colloid Monolayers: An Approach to SERS
Substrates’, Science, 267, 1629–1632 (1995).
170. Y. Wang, S. Schlücker, ‘Rational Design and Synthesis of
SERS Labels’, Analyst, 138, 2224–2238 (2013).
171. W. Xie, S. Schlucker, ‘Medical Applications of Surface-
enhanced Raman Scattering’, Phys. Chem. Chem. Phys.,
15, 5329–5344 (2013).
172. H. Duan, H. Hu, K. Kumar, Z. Shen, J.K. Yang, ‘Direct
and Reliable Patterning of Plasmonic Nanostructures
with Sub-10-nm Gaps’, ACS Nano, 5, 7593–7600 (2011).
173. S. Mahajan, M. Abdelsalam, Y. Suguwara, S. Cintra, A.
Russell, J. Baumberg, P. Bartlett, ‘Tuning Plasmons on
Nano-Structured Substrates for nir-SERS’, Phys. Chem.
Chem. Phys., 9, 104–109 (2007).
174. J.Y. Huang, C. Zong, L.J. Xu, Y. Cui, B. Ren, ‘Clean
and Modified Substrates for Direct Detection of Living
Cells by Surface-enhanced Raman Spectroscopy’, Chem.
Commun., 47, 5738–5740 (2011).
175. W. Zhang, A. Vivoni, J.R. Lombardi, R.L. Birke, ‘Time-
Resolved SERS Study of Direct Photochemical Charge
Transfer Between fmn and a ag Electrode’, J. Phys.
Chem., 99, 12846–12857 (1995).
176. W.B. Cai, B. Ren, X.Q. Li, C.X. She, F.M. Liu, X.W. Cai,
Z.Q. Tian, ‘Investigation of Surface-enhanced Raman
Scattering from Platinum Electrodes Using a Confocal
Raman Microscope: Dependence of Surface Roughening
Pretreatment’, Surf. Sci., 406, 9–22 (1998).
177. P. Hildebrandt, M. Stockburger, ‘Surface-enhanced
Resonance Raman Spectroscopy of Rhodamine 6g
Adsorbed on Colloidal Silver’, J. Phys. Chem., 88,
5935–5944 (1984).
178. N. Félidj, J. Aubard, G. Lévi, J.R. Krenn, M. Salerno,
G. Schider, B. Lamprecht, A. Leitner, F.R. Aussenegg,
‘Controlling the Optical Response of Regular Arrays of
Gold Particles for Surface-enhanced Raman Scattering’,
Phys. Rev. B, 65, 075419 (2002).
179. R.F. Aroca, ‘Plasmon Enhanced Spectroscopy’, Phys.
Chem. Chem. Phys., 15, 5355–5363 (2013).
32
180. C.J. Constantino, T. Lemma, P.A. Antunes, R. Aroca,
‘Single-Molecule Detection Using Surface-enhanced
Resonance Raman Scattering and Langmuir-Blodgett
Monolayers’, Anal. Chem., 73, 3674–3678 (2001).
181. E.C. Le Ru, M. Meyer, P.G. Etchegoin, ‘Proof of
Single-Molecule Sensitivity in Surface Enhanced Raman
Scattering (SERS) by Means of a Two-analyte Tech-
nique’, J. Phys. Chem. B, 110, 1944–1948 (2006).
182. J.E. Bohn, E.C. Le Ru, P.G. Etchegoin, ‘A Statistical
Criterion for Evaluating the Single-Molecule Character
of SERS Signals’, J. Phys. Chem. C, 114, 7330–7335
(2010).
183. S.R. Emory, R.A. Jensen, T. Wenda, M. Han, S.
Nie, ‘Re-examining the Origins of Spectral Blinking
in Single-Molecule and Single-Nanoparticle SERS’,
Faraday Discuss., 132, 249–259 (2006).
184. S.M. Stranahan, K.A. Willets, ‘Super-Resolution Optical
Imaging of Single-Molecule SERS Hot Spots’, Nano Lett.,
10, 3777–3784 (2010).
185. S.L. Kleinman, E. Ringe, N. Valley, K.L. Wustholz, E.
Phillips, K.A. Scheidt, G.C. Schatz, R.P. Van Duyne,
‘Single-Molecule Surface-enhanced Raman Spectroscopy
of Crystal Violet Isotopologues: Theory and Experiment’,
J. Am. Chem. Soc., 133, 4115–4122 (2011).
186. P.G. Etchegoin, E.C. Le Ru, M. Meyer, ‘Evidence
of Natural Isotopic Distribution from Single-Molecule
SERS’, J. Am. Chem. Soc., 131, 2713–2716 (2009).
187. B. Pettinger, ‘Single-Molecule Surface- and Tip-enhanced
Raman Spectroscopy’, Mol. Phys., 108, 2039–2059 (2010).
188. S. Zou, M.J. Weaver, ‘Surface-enhanced Raman Scat-
tering on Uniform Transition-metal films: Toward a
Versatile Adsorbate Vibrational Strategy for Solid-
nonvacuum Interfaces?’, Anal. Chem., 70, 2387–2395
(1998).
189. B. Pettinger, P. Schambach, C.J. Villagómez, N. Scott,
‘Tip-enhanced Raman Spectroscopy: Near-Fields Acting
on a Few Molecules’, Annu. Rev. Phys. Chem., 63,
379–399 (2012).
190. R.M. Stöckle, Y.D. Suh, V. Deckert, R. Zenobi,
‘Nanoscale Chemical Analysis by Tip-enhanced Raman
Spectroscopy’, Chem. Phys. Lett., 318, 131–136 (2000).
191. M.S. Anderson, ‘Locally Enhanced Raman Spectroscopy
with an Atomic Force Microscope’, Appl. Phys. Lett., 76,
3130–3132 (2000).
192. N. Hayazawa, Y. Inouye, Z. Sekkat, S. Kawata,
‘Metallized Tip Amplification of Near-Field Raman
Scattering’, Opt. Commun., 183, 333–336 (2000).
193. B. Pettinger, G. Picardi, R. Schuster, G. Ertl, ‘Surface
Enhanced Raman Spectroscopy: Towards Single Molec-
ular Spectroscopy’, Electrochemistry, 68, 942–949 (2000).
194. A.V. Ermushev, B.V. Mchedlishvili, V.A. Oleinikov,
A.V. Petukhov, ‘Surface Enhancement of Local Optical
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
RAMAN SPECTROSCOPY
Fields and the Lightning-rod Effect’, Quantum Electron.,
23, 435 (1993).
195. Z. Liu, ‘Tip-enhanced Raman Spectroscopy for Single-
molecule Studies: Instrumentation and Applications’, PhD
Thesis, Department of Chemistry, Xiamen University,
Xiamen, (2010).
196. J. Steidtner, B. Pettinger, ‘Tip-enhanced Raman Spec-
troscopy and Microscopy on Single dye Molecules with
15 nm Resolution’, Phys. Rev. Lett., 100, 236101 (2008).
197. B. Ren, G. Picardi, B. Pettinger, R. Schuster, G. Ertl,
‘Tip-enhanced Raman Spectroscopy of Benzenethiol
Adsorbed on au and pt Single-Crystal Surfaces’, Angew.
Chem. Int. Ed., 44, 139–142 (2005).
198. B.-S. Yeo, J. Stadler, T. Schmid, R. Zenobi, W.
Zhang, ‘Tip-enhanced Raman Spectroscopy: Its Status,
Challenges and Future Directions’, Chem. Phys. Lett.,
472, 1–13 (2009).
199. W. Zhang, B.S. Yeo, T. Schmid, R. Zenobi, ‘Single
Molecule Tip-enhanced Raman Spectroscopy with Silver
Tips’, J. Phys. Chem. C, 111, 1733–1738 (2007).
200. C.C. Neacsu, J. Dreyer, N. Behr, M.B. Raschke,
‘Scanning-Probe Raman Spectroscopy with Single-
Molecule Sensitivity’, Phys. Rev. B, 73, 193406 (2006).
201. J. Stadler, T. Schmid, R. Zenobi, ‘Developments in
and Practical Guidelines for Tip-enhanced Raman
Spectroscopy’, Nanoscale, 4, 1856–1870 (2012).
202. B. Pettinger, G. Picardi, R. Schuster, G. Ertl, ‘Surface-
enhanced and STM-tip-enhanced Raman Spectroscopy
at Metal Surfaces’, Single Molecules, 3, 285–294 (2002).
203. B. Pettinger, B. Ren, G. Picardi, R. Schuster, G. Ertl, ‘Tip-
enhanced Raman Spectroscopy (TERS) of Malachite
Green Isothiocyanate at Au(111): Bleaching Behavior
Under the Influence of High Electromagnetic Fields’, J.
Raman Spectrosc., 36, 541–550 (2005).
204. B. Pettinger, B. Ren, G. Picardi, R. Schuster, G.
Ertl, ‘Nanoscale Probing of Adsorbed Species by Tip-
enhanced Raman Spectroscopy’, Phys. Rev. Lett., 92,
096101 (2004).
205. A. Hartschuh, E.J. Sánchez, X.S. Xie, L. Novotny, ‘High-
resolution Near-Field Raman Microscopy of Single-
Walled Carbon Nanotubes’, Phys. Rev. Lett., 90, 095503
(2003).
206. N. Anderson, A. Hartschuh, S. Cronin, L. Novotny,
‘Nanoscale Vibrational Analysis of Single-Walled Carbon
Nanotubes’, J. Am. Chem. Soc., 127, 2533–2537 (2005).
207. T. Schmid, L. Opilik, C. Blum, R. Zenobi, ‘Nanoscale
Chemical Imaging Using Tip-enhanced Raman Spec-
troscopy: A Critical Review’, Angew. Chem. Int. Ed.,
52, 2–17 (2013).
208. U. Neugebauer, P. Rösch, M. Schmitt, J. Popp, C. Julien,
A. Rasmussen, C. Budich, V. Deckert, ‘On the Way to
Nanometer-sized Information of the Bacterial Surface by
SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS): GENERAL INTRODUCTION
Tip-enhanced Raman Spectroscopy’, ChemPhysChem, 7,
1428–1430 (2006).
209. X.D. Lin, V. Uzayisenga, J.F. Li, P.P. Fang, D.Y.
Wu, B. Ren, Z.Q. Tian, ‘Synthesis of Ultrathin
and Compact Au@MnO2 Nanoparticles for Shell-
isolated Nanoparticle-enhanced Raman Spectroscopy
(SHINERS)’, J. Raman Spectrosc., 43, 40–45 (2012).
210. J.F. Li, S.Y. Ding, Z.L. Yang, M.L. Bai, J.R. Anema,
X. Wang, A. Wang, D.Y. Wu, B. Ren, S.M. Hou, T.
Wandlowski, Z.Q. Tian, ‘Extraordinary Enhancement of
Raman Scattering from Pyridine on Single Crystal Au
and Pt Electrodes by Shell-isolated Au Nanoparticles’, J.
Am. Chem. Soc., 133, 15922–15925 (2011).
211. N.R. Honesty, A.A. Gewirth, ‘Shell-isolated Nanopar-
ticle Enhanced Raman Spectroscopy (SHINERS) Inves-
tigation of Benzotriazole Film Formation on Cu(100),
Cu(111), and Cu(Poly)’, J. Raman Spectrosc., 43, 46–50
(2012).
212. W.E. Doering, S. Nie, ‘Spectroscopic Tags Using Dye-
embedded Nanoparticles and Surface-enhanced Raman
Scattering’, Anal. Chem., 75, 6171–6176 (2003).
213. X. Zhang, J. Zhao, A.V. Whitney, J.W. Elam,
R.P. Van Duyne, ‘Ultrastable Substrates for Surface-
enhanced Raman Spectroscopy: Al2 O3 Overlayers Fabri-
cated by Atomic Layer Deposition Yield Improved
Anthrax Biomarker Detection’, J. Am. Chem. Soc., 128,
10304–10309 (2006).
214. D.Y. Wu, J.F. Li, B. Ren, Z.Q. Tian, ‘Electrochemical
Surface-enhanced Raman Spectroscopy of Nanostruc-
tures’, Chem. Soc. Rev., 37, 1025–1041 (2008).
215. B. Ren, X.F. Lin, Z.L. Yang, G.-K. Liu, R.F. Aroca, B.-W.
Mao, Z.-Q. Tian, ‘Surface-enhanced Raman Scattering in
the Ultraviolet Spectral Region: UV-SERS on Rhodium
and Ruthenium Electrodes:’, J. Am. Chem. Soc., 125,
9598–9599 (2003).
216. L. Cui, S. Mahajan, R.M. Cole, B. Soares, P.N. Bartlett,
J.J. Baumberg, I.P. Hayward, B. Ren, A.E. Russell, Z.Q.
Tian, ‘UV-SERS at Well Ordered pd Sphere Segment
Void (SSV) Nanostructures’, Phys. Chem. Chem. Phys.,
11, 1023–1026 (2009).
217. A. Taguchi, N. Hayazawa, K. Furusawa, H. Ishitobi, S.
Kawata, ‘Deep-UV Tip-enhanced Raman Scattering’, J.
Raman Spectrosc., 40, 1324–1330 (2009).
218. J.M. McMahon, G.C. Schatz, S.K. Gray, ‘Plasmonics in
the Ultraviolet with the Poor Metals Al, Ga, In, Sn, Tl,
Pb, and Bi’, Phys. Chem. Chem. Phys., 15, 5415–5423
(2013).
219. N.J. Halas, S. Lal, W.S. Chang, S. Link, P. Nordlander,
‘Plasmons in Strongly Coupled Metallic Nanostructures’,
Chem. Rev., 111, 3913–3961 (2011).
220. A. Ahmed, R. Gordon, ‘Single Molecule Directivity
Enhanced Raman Scattering Using Nanoantennas’, Nano
Lett., 12, 2625–2630 (2012).
Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276
33
221. S. Berweger, J.M. Atkin, R.L. Olmon, M.B. Raschke,
‘Adiabatic Tip-Plasmon Focusing for Nano-Raman Spec-
troscopy’, J. Phys. Chem. Lett., 1, 3427–3432 (2010).
222. Y. Fang, H. Wei, F. Hao, P. Nordlander, H. Xu, ‘Remote-
Excitation Surface-enhanced Raman Scattering Using
Propagating ag Nanowire Plasmons’, Nano Lett., 9,
2049–2053 (2009).
223. R.R. Frontiera, A.I. Henry, N.L. Gruenke, R.P.
Van Duyne, ‘Surface-enhanced Femtosecond Stimulated
Raman Spectroscopy’, J. Phys. Chem. Lett., 2, 1199–1203
(2011).
224. T. Henkel, A. März, J. Popp, ‘SERS and Microfluidics.’
in Surface Enhanced Raman Spectroscopy:Analytical,
Biophysical and Life Science Applications, 1st edition, ed.
S. Schlücker, Wiley-VCH Verlag GmbH & Co. KGaA,
Berlin, 173–190, 2010.
225. I. White, S. Yazdi, W. Yu, ‘Optofluidic SERS: Synergizing
Photonics and Microfluidics for Chemical and Biological
Analysis’, Microfluid. Nanofluidics, 13, 205–216 (2012).
226. D. Cialla, A. März, R. Böhme, F. Theil, K. Weber, M.
Schmitt, J. Popp, ‘Surface-enhanced Raman Spectroscopy
(SERS): Progress and Trends’, Anal. Bioanal. Chem., 403,
27–54 (2012).
227. T.A. Yano, P. Verma, Y. Saito, T. Ichimura, S. Kawata,
‘Pressure-assisted Tip-enhanced Raman Imaging at a
Resolution of a Few Nanometres’, Nat. Photon., 3,
473–477 (2009).
228. M. Osawa, ‘Near-Field Optics and Surface Plasmon
Polaritons’, Appl. Phys., 81, 163–187 (2001).
229. M. Osawa, ‘Dynamic Processes in Electrochemical Reac-
tions Studied by Surface-enhanced Infrared Absorption
Spectroscopy (SEIRAS)’, Bull. Chem. Soc. Jpn., 70,
2861–2880 (1997).
230. S. Nie, L.A. Lipscomb, N.T. Yu, ‘Surface-enhanced
Hyper-Raman Spectroscopy’, Appl. Spectrosc. Rev., 26,
203–276 (1991).
231. W.-H. Li, X.-Y. Li, N.-T. Yu, ‘Surface-enhanced Hyper-
Raman Scattering and Surface-enhanced Raman Scat-
tering Studies of Electroreduction of Phenazine on Silver
Electrode’, Chem. Phys. Lett., 327, 153–161 (2000).
232. S. Baldelli, A.S. Eppler, E. Anderson, Y.-R. Shen, G.A.
Somorjai, ‘Surface Enhanced Sum Frequency Generation
of Carbon Monoxide Adsorbed on Platinum Nanoparticle
Arrays’, J. Chem. Phys., 113, 5432–5438 (2000).
233. E.J. Liang, A. Weippert, J.M. Funk, A. Materny, W.
Kiefer, ‘Experimental Observation of Surface-enhanced
Coherent Anti-Stokes Raman Scattering’, Chem. Phys.
Lett., 227, 115–120 (1994).
234. J. Yelk, M. Sukharev, T. Seideman, ‘Optimal Design of
Nanoplasmonic Materials Using Genetic Algorithms as a
Multiparameter Optimization Tool’, J. Chem. Phys., 129,
064706–064707 (2008).
34 RAMAN SPECTROSCOPY

235. J.R. Lombardi, R.L. Birke, ‘The Theory of Surface-
enhanced Raman Scattering’, J. Chem. Phys., 136,
144704–144711 (2012).
236. S.M. Morton, D.W. Silverstein, L. Jensen, ‘Theoret-
ical Studies of Plasmonics Using Electronic Structure
Methods’, Chem. Rev., 111, 3962–3994 (2011).
237. S.M. Morton, L. Jensen, ‘A Discrete Interaction
Model/Quantum Mechanical Method to Describe the
Interaction of Metal Nanoparticles and Molecular
Absorption’, J. Chem. Phys., 135, 134103–134112 (2011).

Encyclopedia of Analytical Chemistry, Online © 2006–2013 John Wiley & Sons, Ltd.
This article is © 2013 John Wiley & Sons, Ltd.
This article was published in the Encyclopedia of Analytical Chemistry in 2013 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470027318.a9276