Multifunctional plasmonic sensors on low-cost subwavelength metallic nanoholes arrays
Transcript of Multifunctional plasmonic sensors on low-cost subwavelength metallic nanoholes arrays
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Multifunctional plasmonic sensors on low-cost subwavelength metallicnanoholes arrays
Valentin Canpean* and Simion Astilean
Received 15th July 2009, Accepted 14th September 2009
First published as an Advance Article on the web 15th October 2009
DOI: 10.1039/b914235e
Localized surface plasmon resonance (LSPR) sensing is combined with surface enhanced Raman
scattering (SERS) detection on periodic arrays of subwavelength metallic nanoholes for the first time.
LSPR sensors provide detection of molecular adsorption in both transmission and reflectivity modes
with sensitivity greater that 300 nm/RIU and a spectral shift of 16 nm in the case of binding
a monolayer of p-aminothiophenol (p-ATP) molecules. Subsequent SERS analysis enables
identification of the adsorbed p-ATP molecule, its structure and orientation on the metal surface.
This synergistic LSPR–SERS approach on low-cost metallic films perforated with periodic arrays of
subwavelength nanoholes opens a route for molecular dual-modal detection to be integrated in
lab-on-chip systems to increase the reliability of biological detection.
Introduction
The development of highly selective and sensitive sensors is of
foremost importance for medical diagnostics, environmental
protection, drug screening or food safety.1 Much sensor research
has been devoted to the evaluation of various signal transduction
methods including optical, radioactive, piezoelectric, and
magnetic. Strategies for the development of sensing devices that
can detect the analyte species without labelling, i.e. label-free
detection, are of significant interest. Optical sensors based on
plasmonic transducers are fast becoming the method of choice in
non-labelling analysis of biomolecular interaction.2,3 In
conjunction with plasmonic transduction based on excitation of
surface plasmons on planar gold surface in conventional surface
plasmon resonance (SPR) devices (see ref. 4 and references
therein), recently there has been an increasing interest in optical
nano-sensors based on localized surface plasmon resonance
(LSPR) in nanometer-sized metallic structures.5–8 On the other
hand, surface-enhanced Raman scattering (SERS), with its great
ability to detect single molecules, has been proved to have great
potential in label-free ultrasensitive biomolecule detection.9,10 In
recent years the interest in LSPR and SERS-based sensors was
completely revived, mainly because the accumulated experi-
mental data has clearly demonstrated the huge potential of both
methods in surface science, analytical and environmental
applications, biomedicine, biophysics and biochemistry.
The main optical signature of metallic nanoparticles is a strong
UV-VIS-NIR extinction band that is not present in the spectrum
of the bulk metal. Such optical response results when the
frequency of the incident photon is resonant with the collective
oscillation of the conduction electrons, and is known as localized
surface plasmons resonance. The peak extinction wavelength
(lmax) of the LSPR spectrum is strongly dependent upon the size
Babes-Bolyai University, Faculty of Physics and Institute forInterdisciplinary Experimental Research, 42 Treboniu Laurian, 400271Cluj-Napoca, Romania. E-mail: [email protected];Fax: +40(264) 591906; Tel: +40(264)454554/119
3574 | Lab Chip, 2009, 9, 3574–3579
and shape of the nanoparticle, as well as the interparticle spacing
and dielectric function of the local environment.11,12
The LSPR sensing mechanism is based on the modification of
the electromagnetic field decay length when adsorbate molecules
come in contact with the surface of metal. In the case of nano-
particles, the local electromagnetic field operates in a manner
analogous to propagating surface plasmon-polaritons (SPP) on
a flat metallic film and enables the transduction of chemical
binding events into a measurable wavelength shift of the extinc-
tion peak. Although many effective nanoparticle-based LSPR
biosensors have been demonstrated at laboratory level13,14 the
practical implementation of LSPR instrumentation still requires
large improvement regarding reproducibility, spatial resolution
and monodispersity in size and shape of nanoparticles. However,
similar plasmonic response can be devised from much more stable
and reproducible metallic nanostructures which are continuous
metallic films perforated with regular arrays of subwavelength
nanoholes, rather than assemblies of nanoparticles. In contrast to
conventional SPR devices, a continuous metallic film perforated
with regular arrays of subwavelength nanoholes can operate
without requiring a prism for plasmon coupling, requiring only
simple reflection or transmission configurations. In this case
a UV-Visible microspectrometer can be efficient enough to obtain
the signal and, therefore, the experimental setup can be more
easily integrated into portable, low-cost devices for rapid bio-
analytical measurements.15,16 Furthermore, short-range ordered
nanoholes in thin metal films can be inexpensively fabricated with
colloidal lithography techniques over large area.17,18
Besides many interesting optical features,19–22 the excitation of
surface plasmon modes in nanohole arrays exhibits a very
sensitive response to the refractive index of a thin molecular layer
located within a few nm of the metal. In particular when metal
films are sufficiently thin (films become semitransparent even in
the absence of holes), in addition to exciting surface plasmon-
polariton (SPP) modes by two dimensional grating scattering,
there is also the possibility to excite localised modes (LSPR)
associated with the hole cavities.23 A hole in thin film actually
This journal is ª The Royal Society of Chemistry 2009
Fig. 1 AFM image of metallic film perforated with an array of holes.
The scale bar is 1 mm.
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exhibits a resonant scattering spectrum that is qualitatively
similar to a particle of approximately the same dimensions and
such resonance can be also assigned to LSPR.24 Notably, the
optical excitation of the LSPR associated with the hole cavity
results in not only a UV-VIS extinction band, but also strong
enhancement of the local electromagnetic field for operation in
SERS. As a result a noble metallic film perforated with sub-
wavelength nanohole arrays are attractive substrates for both
plasmonic and SERS sensing. Indeed, many examples of nano-
hole arrays have been previously studied with specific regard to
either LSPR or SERS operation. Pang et al. demonstrated the
applicability of periodic arrays of metallic nanoholes as plas-
monic sensors by monitoring protein–protein specific bonding.25
Brolo and co-workers demonstrated the enhanced-Raman
scattering from molecules adsorbed on arrays of nanoholes in
noble-metal thin films.26
To the authors’ knowledge, work aiming to demonstrate that
both sensing abilities, namely plasmonic (LSPR) and SERS
detection, can be integrated onto the same periodic array of
nanoholes, has not been reported so far. However, the combining
of LSPR sensing with SERS molecular identification can expand
the range of applications, allowing analyte identification and
improvement of the detection limits, especially for low molecular
weight molecules. Moreover, metallic films perforated with peri-
odic arrays of subwavelength nanoholes can be easily integrated
with microfluidics for portable lab-on-a-chip applications.16,27
The present work implements a synergistic LSPR–SERS
approach on short-range ordered nanoholes in a thin metal film,
inexpensively fabricated with colloidal lithography techniques.
Primarily, the LSPR bulk sensitivity of the substrate is assessed
by measuring important shifts in transmission and reflectivity as
function of the refractive index changes when the film was
immersed in different liquids. Secondly, the LSPR surface
sensitivity of the substrate is demonstrated by detecting a single
molecular layer of para-aminothiophenol (p-ATP) adsorbed
onto the film surface. Subsequently the SERS method is
employed to elucidate the structure and orientation of p-ATP on
the metal surface.
Experimental
The method for experimentally fabricating the array of nano-
holes is explained in detail elsewhere.18 Briefly, our approach
consists of four steps: (1) convective assembly of a monolayer of
polystyrene spheres of 450 nm diameter on a microscope slide;
(2) reactive ion etching of the substrate in oxygen plasma to tailor
the polystyrene spheres to the desired size (diameter 320 nm);
(3) gold film evaporation at chosen thickness (here 40 nm) onto
the previously etched substrate and (4) removal of the poly-
styrene spheres by sonication in toluene to leave behind a regular
distribution of nanoholes in the deposited Au film. Fig. 1 shows
a typical AFM image of the metallic nanohole arrays. The film in
Fig. 1 exhibits some patterning ‘‘defects’’ which were transferred
to the metallic structure from the crystallization imperfections
(gaps between crystalline domains or missing spheres) which
existed in the initial colloidal mask. Typically for a very good
quality sample such defects represent only a small percentage of
the area of the highly ordered close-packed crystal. Film thick-
ness measured by atomic force microscopy (alpha 300 AFM
This journal is ª The Royal Society of Chemistry 2009
module from Witec) was found to agree closely with thicknesses
measured during evaporation. In this study a film thickness of
40 nm, an array period of 450 nm and a hole diameter of 320 nm
were chosen in a trade-off between direct transmission efficiency,
dynamic range of our spectrometer and wavelength of laser line
available for Raman excitation. For transmission and reflection
measurements, a drop of liquid was inserted between two
microscope slides, one of them sustaining the metal film with the
array of sub-wavelength holes. The optical spectra were
measured at normal incidence and unpolarized light with
a miniature spectrometer (Ocean Optics USB4000 UV-VIS). The
spectrometer was equipped for transmission with two QP100-2-
VIS/BX optical fibers with core diameters of 100 mm (one fiber
serving for sample illumination and one for reading the trans-
mitted light) and with a QR200-7-VIS/BX reflection optical fiber
probe consisting of a tight bundle of 7 optical fibers of 200 mm
diameter (6 illumination fibers around 1 read fiber) for back
reflectivity measurement. The spectra were normalized against
a reference sample consisting of bare glass slides for transmission
and an optically thick gold film for reflectivity measurements.
For Raman measurement, the sample consisting of metallic
nanohole arrays deposited on microscope slide was first immersed
in a 10�3 M p-ATP solution in methanol for 3 h, then rinsed to
ensure one molecular layer was adsorbed on the metallic surface.
Raman spectra were obtained in backscattering geometry with
a WiTec CRM 200 Confocal Raman Microscope equipped with
a Raman Spectroscopy System UHTS 300 charge coupled device
(CCD) operating at �60 �C, using a 632.8 nm He–Ne laser as
excitation source. All measurements were conducted using
a 20� microscope objective with a numerical aperture of 0.4.
Results and discussion
Fig. 2 depicts the normalized optical transmission and reflectivity
of a perforated metallic film recorded in air (reference spectrum)
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Fig. 2 (a) Transmission and (b) reflectivity spectra of a metallic array of nanoholes at various refractive indices: (A) 1, (B) 1.333, (C) 1.343, (D) 1.357,
(E) 1.371, (F) 1.385, (G) 1.399, (H) 1.414, (I) 1.428. The spectra were vertically translated for clarity.
Fig. 3 Dependence of the plasmon resonance wavelength on the
refractive index in transmission and reflectivity modes.
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and in liquids of different refractive indices. Water–glycerol
mixtures of varying volume ratios were used to tune into different
effective refractive indices from 1.333 (for pure water) to 1.473 (for
pure glycerol), according to the Lorentz–Lorenz formula.28 While
a flat film exhibits the well-known characteristics of semi-
transparent thin films (transparency in the green at 510 nm and
high reflectivity at longer wavelengths), the optical spectra of the
perforated film of the same thickness appear to be significantly
altered. For normal incidence investigation the structure’s dif-
fractive modes cut-off at the wavelength given by eqn (1):
lmax ¼ 2pnef/Gij (1)
where the first evanescent modes (SPP propagative modes) occur
at the metal/liquid interface.
Here
Gij ¼�
4p=ffiffiffi3p
D� ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
i2 þ j2 þ ijp
(2)
is the reciprocal vector of the grating, integers i and j are for the
SPP first-order (0, �1), nef is the effective index of water–glycerol
solution and D is the diameter (450 nm) of the polystyrene sphere
which determines the grating periodicity. The above relation
gives cut-off wavelengths (lmax) ranging from 520 to 553 nm
when the effective index varies between 1.333 and 1.428. Each of
the spectra presented in Fig. 2 exhibit maxima and minima of
interest at wavelengths at which the grating is non-diffractive,
namely the perforated film behaves like a zero-order grating and,
consequently, no diffraction orders into the far-field are possible.
Therefore we have only to analyse light that is transmitted and
back reflected into the zeroth orders.
We can attribute the strong wavelength dependent modula-
tions between 550 and 800 nm to excitation of surface plasmon
modes although it is not clear how much contribution comes
from localized (LSPR) and propagative (SPP) plasmon reso-
nances. It is important to note that the position of transmission
and reflection maxima/minima does not coincide with the reso-
nances provided by the grating equation because of coupling
between propagating SPPs and LSPR. Moreover, in a previous
study we have shown that the position and intensity of trans-
mission maxima varies with the hole diameter,18 which is also
explained by the coupling between LSPR and SPPs.
3576 | Lab Chip, 2009, 9, 3574–3579
We find a linear red-shift of the minima and maxima in
transmission and reflectivity as function of the increasing effec-
tive refractive index (see Fig. 3) which allows us to calculate the
bulk sensitivity in transmission (338 nm/RIU) and reflectivity
(301 nm/RIU). The two values are slightly different, which can be
related to different numerical apertures of optical fibres for light
collection in transmission and reflection experiments. The plas-
monic sensitivity is similar with previously reported data for
a nanohole array (333 nm/RIU) and gold nanoshells (328 nm/
RIU) but it is higher that of regular arrays of metallic nano-
particles prepared by standard nanosphere lithography (191 nm/
RIU)11 or gold nanorods (195–288 nm/RIU) and colloids
(66.5 nm/RIU) deposited on a solid substrate.29
In the next step we explore the limit of detection when
a monolayer of probe molecules (p-ATP) was absorbed onto the
film. A shift of 16 nm was measured between the transmission
maximum recorded before and after the adsorption of p-ATP
(see Fig. 4).
From the shift value and the liner dependence of bulk sensi-
tivity in Fig. 3, an effective refractive index of 1.188 for a mono-
layer of p-ATP is determined.
This journal is ª The Royal Society of Chemistry 2009
Fig. 4 Normalized transmission spectra through a metallic array of
nanoholes without (—) and with an adsorbed p-ATP monolayer (----).
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The result can be compared with the value given by a theo-
retical approach from literature for determining the effective
refractive index.30 Accordingly, the effective refractive index of
a thin molecular layer can be calculated using eqn (3):
neff ¼2
ld
ðN0
nðzÞ�expð�z=ldÞ
�2dz (3)
where
nðzÞ ¼ncap; 0 # z # dcap
nair; dcap # z\N
((4)
Here ncap is the bulk refractive index of p-ATP (ncap¼ 1.665), nair
is the refractive index of air (nair ¼ 1.000), dcap represents the
thickness of the capping molecular monolayer of p-ATP (dcap ¼0.667 nm) and ld represents the characteristic decay length (ld �5 nm) of the electromagnetic field. From the above equation we
Fig. 5 (a) Normal Raman spectrum of solid p-ATP (----) and SERS spect
(b) Simulation of the electric field |Ez| (normalized by the Fourier transform
This journal is ª The Royal Society of Chemistry 2009
found an effective refractive index of 1.155, which is close to the
experimental determination.
Although the plasmon resonance shift provides high sensi-
tivity, this sensing mechanism lacks molecular specificity. On the
contrary, SERS offers enormous molecular information about
the analyte, as the SERS signal results directly from the molec-
ular vibration when molecules are in close proximity to nano-
meter-sized metallic structures. Fig. 5(a) presents the recorded
SERS spectrum of p-ATP together with its corresponding ordi-
nary Raman spectrum collected from a bulk sample. We are
aware about the fact that when excited by laser, the small amount
of ‘‘defects’’ existing in the patterned film are able to sustain and
concentrate a much higher electric field in such localized surface
plasmon resonances and increase the Raman signal. Therefore,
in order to check the reproducibility of the recorded signal, many
SERS spectra were collected from different spots on the nano-
structured film. The recorded spectra exhibit only small varia-
tions (<10%) of the relative intensities of the bands from spot to
spot, while the spectral position and width of the Raman bands
show no noticeable differences. The result clearly demonstrates
two aspects: (a) the main Raman signal is generated and
controlled by periodic plasmonic interactions with little contri-
bution from the randomly distributed, local defects mentioned
previously, and (b) the molecular surface coverage is consistent
with a uniform monolayer of self-assembled target analyte.
Relative to the ordinary Raman spectrum, the most noticeable
differences in the SERS spectrum are the frequency shifts and
changes in relative intensity for most of the bands. The C–S
stretching vibrations mode shifts from 1093 to 1080 cm�1,
whereas the C–C stretching vibrations band shifts from 1596 to
1581 cm�1. It was shown that the enhancement of the p-ATP
Raman bands located at 1080 and 1581 cm�1 assigned to the C–S
stretching vibration has a pure electromagnetic origin.31 The
absence of the S–H stretching band at 2580 cm�1, corroborated
with the enhancement of the C–S stretching mode at 1080 cm�1,
demonstrates that the p-ATP molecules are adsorbed onto the
gold film through their sulfur atoms. There is also an enhance-
ment of the bands around 1147, 1391 and 1440 cm�1 which are
rum of p-ATP molecules adsorbed on a metallic nanohole array (—).
of the source pulse) at the metal/air interface (0xy plane) at l ¼ 633 nm.
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conventionally ascribed to the charge transfer from the metal to
the adsorbed molecules. It should be noted that the UV-Vis
absorption spectrum of the p-ATP molecule presents two bands
around 256 and 297 nm and thus no resonant Raman contri-
bution would be involved in the overall SERS enhancement at
633 nm excitation.
However, for a molecule adsorbed onto a metal, vibronic
mixing between the electronic and vibrational wave functions of
adsorbed molecules and those of the metal leads to electron
transfer, strongly increasing Raman scattering associated with
mixed modes by inducing an effect analogous to resonant
Raman. The apparent enhancement of the bands around
1147 cm�1 (ascribed to C–H bending) and 1391 and 1440 cm�1
(ascribed to a combination of the phenyl group C–C stretching
and NH2 rocking) together with the decrease of the intensity of
the band around 1190 cm�1 (ascribed to C–N stretching)
demonstrates that there is at least a subset of molecules which
adopt a tilted orientation relative to the metal surface. Normally,
p-ATP molecules should orient perpendicular to the metal
surface in a close-packed molecular layer, making it difficult for
a molecule to tilt toward the metal surface. However, it is
conceivable that at rims of hole cavities, the close-packing could
be interrupted, allowing molecules to lie flat on the surface and
undergo charge transfer. In order to get a better insight into the
amplification and localization of the electromagnetic field inside
and near the rims of metallic holes, numerical simulations by
employing the FDTD method were conducted, using FDTD-
Solutions� software from Lumerical Inc.32 The simulated
structure consisted of a thin gold film of 40 nm thickness,
perforated with a periodic array of cylindrical holes with diam-
eters of 320 nm sandwiched between two infinite half-spaces of
air and glass. The rectangular computational cell used had
dimensions of 152 � 262 � 224 grid points spaced at 3 nm
distance from each other. Perfectly matched layer (PML)
boundary conditions were applied on the boundaries normal to
the incident light to prevent reflections (z direction) and periodic
boundary conditions were applied in the x and y directions. A
frequency domain profile monitor at the air/metal interface was
used to record the fields. Numerical calculations in Fig. 5(b)
showed that the plasmonic electric field at the metal/air interface,
excited by laser line at 633 nm is located near the contour of
circular holes and exhibits a multipolar like configuration.
Indeed, this theoretical result implies that the majority of the
SERS signal measured from our sample is due to the excitation of
a very small percentage of the adsorbed molecules adsorbed near
the edges of the holes.
We estimate the SERS enhancement factor (EF) per adsorbed
molecule using eqn (5):33
EF ¼ ASERS
Nsurf
Nbulk
Anorm
(5)
where ASERS, Anorm, Nbulk and Nsurf are the SERS and normal
Raman areas of the n(CS) band and the number of the probe
molecules under laser illumination in the bulk sample and
adsorbed on the substrate, respectively. For the normal Raman
experiment, the probe volume was considered a focal ‘‘tube’’ with
a waist diameter of �5 mm and a depth of �19 mm. By using the
density of the bulk sample, Nbulk was calculated, yielding 2.13� 1012
molecules. In order to estimate Nsurf we considered that only the
3578 | Lab Chip, 2009, 9, 3574–3579
molecules adsorbed on the inner surface of the holes and those
adsorbed near the edge of the holes contribute to the SERS
enhancement. Given the diameter of the holes (320 nm), the
height of the holes (40 nm), the diameter of the corona (consid-
ered as 2 nm), the diameter of the spot (5 mm) and the area
occupied by each p-ATP molecule (�0.39 nm2)34 we calculated
Nsurf�1.33� 107 molecules. Thus we calculated an enhancement
factor of 2 � 104, which is in good agreement with similar results
obtained previously on regular arrays of nanoparticles.26
Future work will be focused on increasing the sensitivity of the
fabricated structures upon changes in the refractive index of the
local environment and SERS activity by optimizing the size of
the holes, the period of the hole array, as well as the thickness of
the metallic film. As regard to considering the above fabricated
substrate as a potent biosensing platform for SERS, the issue of
the reproducibility of the spectral response from the target
biomolecule can arise in some cases. There are two standard
SERS configurations that have to be addressed. First, for
detecting small biomolecules (nucleic acid bases, amino acids and
pharmaceuticals) the bio-analyte can be directly linked to the
nanostructured surface, as in the case of the p-ATP probe
molecule, and the analyze should work well.35 As for proteins,
a typical kind of biomacromolecule, most of them have three-
dimensional structures of large diameters (2–20 nm) which can
lead to different orientations and structural changes on the
surface and, consequently, to differences in selective enhance-
ments of certain molecular groups. This obstacle may be over-
come by employing analyte capture methods, e.g. using specific
molecular linkers such as antibodies and taking into account the
statistical reliability of the method. Solutions for these critical
issues are currently addressable in SERS literature36 and the
extension of this work to detection of proteins is now in progress
in our laboratory.
Conclusions
We have reported a study on the optical and spectroscopic
properties of regular arrays of subwavelength holes in a thin gold
film with the aim of exploiting the entire sensing ability of such
a substrate by combining LSPR and SERS. The binding of the
p-ATP monolayer was quantified by SPR shift measurements
and SERS was used to verify the identity and orientation of the
adsorbed molecules. Apart from LSPR sensitivity of the
substrate, which can detect the presence of a thin layer of p-ATP
molecules, the SERS has the ability to detect the p-ATP mole-
cules at much lower concentration and provide more molecular
specific information.
We have successfully demonstrated the integration of a LSPR
transducer with SERS activity on low-cost subwavelength metallic
nanohole arrays. The feasibility of such an approach can contribute
to the development of new multifunctional sensing platforms, not
only for signalling molecular binding events, but also elucidating the
orientation of molecular species at a metal surface.
Acknowledgements
This work was supported by The National University Research
Council (CNCSIS) from Romania in the frame of the PN-II
program (Project No. 477/2007 and Project TD-28/2007).
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