High-resolution fiber optic surface plasmon resonance sensor for biomedical

applications
Kirill A. Tomyshev, Diana K. Tazhetdinova, Egor S. Manuilovich, and Oleg V. Butov

Citation: Journal of Applied Physics 124, 113106 (2018); doi: 10.1063/1.5045180

View online: https://doi.org/10.1063/1.5045180
View Table of Contents: http://aip.scitation.org/toc/jap/124/11
Published by the American Institute of Physics
 JOURNAL OF APPLIED PHYSICS 124, 113106 (2018)

High-resolution fiber optic surface plasmon resonance sensor for biomedical

applications
Kirill A. Tomyshev,1,2 Diana K. Tazhetdinova,1,2 Egor S. Manuilovich,2 and Oleg V. Butov1,2
1
Kotelnikov Institute of Radioengineering and Electronics of RAS, Mokhovaya 11-7, Moscow 125009, Russia
2
N.M. Emanuel’ Institute of Biochemical Physics of RAS, Kosigyna 4, Moscow 119334, Russia

(Received 18 June 2018; accepted 30 August 2018; published online 19 September 2018)
This paper presents a modified design of a high-resolution fiber optic sensor that operates on the
surface plasmon resonance effect. The sensor is based on the well-known method of generating sur-
face plasmons with the help of an inscribed tilted fiber Bragg grating that excites the cladding
modes. Because the original design solution used a polarizing fiber, it was possible to significantly
improve the stability of the sensor readings. The specialized mathematical apparatus was used to
determine the surface plasmon resonance spectral position. It was experimentally shown that the
limit of detection to the refractive index of such a sensor is 2  106 refractive index units. The
sensor’s response to the investigated medium temperature change is presented and analyzed. The
high resolution of the sensor in detecting protein molecules was demonstrated. Such sensors open
wide perspectives for their application in real high-sensitivity sensor systems as biosensors for
immune analysis in medical diagnostics. Published by AIP Publishing.
https://doi.org/10.1063/1.5045180

I. INTRODUCTION sensor. The result of energy transfer, as a rule, is observed in

Recently, surface plasmon resonance (SPR) has been
actively used as a physical principle for creating various sen-
sors and devices.1–3 Biochemical plasmon resonance-based
sensors used for immunoassay purposes are very popular.4,5
The basic operating principle of such systems is to measure
the frequency of the plasmon-polariton excited on the surface
of the sensor placed into the investigated medium. In accor-
dance with physical principles, this plasmon-polariton fre-
quency depends explicitly on the parameters of the medium,
namely on the average refractive index near the sensor sur-
face.6,7 Obviously, any modification of the surface—in partic-
ular, the adsorption of detectable biomolecules—changes the
sensor readings. Existing analytical complexes of immune
analysis based on planar schemes are actively used in medi-
cine, including the popular Kretschmann scheme.6 However,
such equipment is characterized by high complexity and price
as well as lack of mobility, while the actual task is to create
compact, mobile, and reasonable devices for conducting
express analysis directly where it is necessary. According to
this approach, fiber optic technologies seem to be the most
promising direction in the development of the plasmon-based
sensors.
The literature includes many studies devoted to plasmon-
based fiber sensors.3,8–14 In such sensors, the energy of the eva-
nescent light field is used to generate plasmon polaritons on
the surface of the optical fiber. To achieve the generation con-
ditions, the surface is covered with a thin layer of plasmon
metal, usually gold. The frequency of the emerging surface
plasmons depends on the refractive index of the external
medium, as in the case of the planar schemes. Effective energy
transfer takes place when the resonance condition is achieved,
in which the optical radiation’s phase velocity coincides with
the plasmon’s propagation velocity along the surface of the
the sensor’s transmission spectrum. Considering that a plas-
mon’s propagation velocity depends on the parameters of the
media surrounding the sensor, its change also causes a change
in the fiber sensor’s transmission spectrum.
Many solutions are suitable to create the conditions for
the evanescence of a light field from a fiber, such as shaping
the fiber surface, thermal tapering, and partial or complete
removal of the cladding.8 The design of particular interest
includes structures using tilted fiber Bragg gratings.15–18 Such
a grating excites a discrete set of cladding modes, which can
be observed on the transmission spectrum as a sequence of
spectral loss peaks.19 The cladding modes, whose projection
of the phase velocity on the fiber surface coincides with the
phase velocity of the surface plasmon, effectively excite it. In
this case, the energy of the optical radiation is transferred to
the energy of the surface plasmon. On the transmission spec-
trum, such resonance generation looks like a characteristic
“constriction” (Fig. 1), the spectral position of which, in gen-
eral, depends directly on the refractive index of the surround-
ing medium. By observing the spectral position of the
constriction and its change, it is possible to reveal processes,
such as the adsorption of protein molecules on the sensor sur-
face.20–23 Sensors based on this principle are some of the most
promising for applications in fiber biosensor systems.
Although numerous publications have demonstrated
excellent results on the sensors’ operation in laboratory con-
ditions, they have not yet been practically implemented. This
is due to a number of unsolved problems, one of which is the
necessity of monitoring the light radiation’s polarization
state, which affects the efficiency of the plasmon resonance
generation. In accordance with the configuration of the
electromagnetic field in surface plasmons, only one of the
linear components of light polarization is capable of partici-
pating in generating plasmons. Using an isotropic optical

0021-8979/2018/124(11)/113106/8/$30.00 124, 113106-1 Published by AIP Publishing.

113106-2 Tomyshev et al.
FIG. 1. Characteristic spectrum of a plasmon sensor based on a tilted fiber
Bragg grating.
fiber—typically standard telecommunications fiber, e.g.,
Corning SMF-2824—one can change the polarization state of
the propagating radiation even through minor deformations,
resulting in significant distortions in the sensor’s transmis-
sion spectrum. This effect significantly impairs the sensor
parameters, such as the resolution and limit of detection
(LOD).
Another important unsolved task is the exact determina-
tion of the plasmon resonance wavelength from the measured
spectrum. To solve this problem, it is necessary to use mathe-
matical processing methods based on complex analysis of the
spectral pattern. Here, it should be mentioned that for many
tasks, it is not so important to measure the exact value of the
plasmon resonance wavelength but rather its change under the
influence of external factors. Thus, the dynamics of the plas-
mon resonance’s spectral position change under the influence
of protein adsorption on the sensor surface can be used to esti-
mate the protein’s initial concentration in solution.
In our work, we propose a solution to maintain the polari-
zation state by using a special polarizing fiber installed
directly before the sensitive part of the sensor. To calculate
the wavelength of the plasmon resonance, an automatic algo-
rithm for processing spectral data is used, based on analysis of
the spectral peaks’ amplitude. Experimental data demonstrat-
ing the sensor’s high resolution and its detection limit with
respect to the refractive index are presented. Also, the applica-
tion of the sensor in detecting low concentrations of protein
molecules (myoglobin) in solution was demonstrated.
II. EXPERIMENTAL SAMPLES
All sensitive elements of the fiber plasmon sensors used
in the experiments were manufactured using the same single
technology. Tilted fiber Bragg gratings were inscribed in
SMF-28, a standard telecommunication fiber. To improve
the efficiency of the grating inscription process, the fiber was
loaded with molecular hydrogen with the help of a special
high-pressure chamber at 12 MPa and 100  C temperature
for 24 h. The grating was inscribed with the help of an ArF-
excimer laser with a radiation wavelength of 193 nm and a
J. Appl. Phys. 124, 113106 (2018)
phase mask technique. To provide the tilt of the grating, both
the mask and the fiber were located at an angle of 17 to the
plane in front of the laser radiation.8 Taking into account the
refractive index of the glass, this led to a tilt angle of 11.3
relative to the plane of the fiber cross-section.
After the inscription, the gratings were covered with a
layer of gold 40 nm thick by means of thermal vacuum evapo-
ration. The fiber’s coated surface was located above the evap-
orator, at a distance of about 10 cm. To ensure better adhesion
of the gold layer to the surface of the optical fiber, an interme-
diate layer of chromium 2–3 nm in thickness was deposited.
The metal layers were applied successively with the help of
two separate evaporators. In order to ensure uniform deposi-
tion of the layer onto the cylindrical surface of the optical
fiber, it was rotated uniformly around its axis above the evapo-
rator with the help of a specially developed rotation mecha-
nism (Fig. 2). The frequency of rotation exceeded the inverse
time of evaporation of the metal by many times.24,25 The
thickness of the deposited metal layer was determined by the
initial mass of the evaporated material.
Typically, measurement with the help of the grating-
assisted plasmon sensor is based on measuring the transmitted
signal,15 since such a sensor, unlike a typical Bragg sensor, does
not have a reflected signal of cladding modes. However, this
measurement scheme has a number of drawbacks due to the
need for using a transmitting fiber both before and after the sens-
ing area and, correspondingly, two sensor attachment points.
The sensor cannot be used as a terminal probe dipstick with an
unfixed sensitive end, which in turn limits the design of the cell
in which the experiment is carried out. Thus, for example, exper-
imenting within an open cell in which a sensor is placed nega-
tively affects measurement accuracy due to increased
evaporation and the impossibility of achieving thermodynamic
equilibrium in the liquid under study. Closed-cell designs for
this type of sensor are difficult to use and require rigid mounting
of the sensor at both ends. The presence of two such mechanical
points of attachment causes, in turn, increased sensitivity of the
sensor to external vibrations and mechanical influences, which
also negatively affects the accuracy of the measurements.
We used a well-known solution, which is to use the
reflected signal to analyze the spectrum. Directly behind the
sensor element, no more than 5 mm from the end of the
Bragg grating, a metal mirror was added to reflect the spec-
trum passed through the sensor. Moreover, after reflection
FIG. 2. Scheme of the fiber rotation mechanism above the evaporator.
113106-3 Tomyshev et al.
from the mirror, the light repeatedly passed through the sen-
sor, increasing the contrast of the spectral pattern. The mirror
was manufactured using the same technology as that used
for the sensor coating. A metal layer was deposited (in our
case, copper) at the cleaved edge of the fiber. A sub-layer of
chromium was also used to ensure increased adhesion of the
metal to the glass. To protect the mirror from possible
mechanical damage, the outside surface of the mirror was
covered with a layer of glue.
III. EXPERIMENTAL SETUP AND DATA PROCESSING
A. Setup for the open-tank experiment
The first experiments with fiber plasmon sensors were
carried out in large open containers, such as petri dishes. The
spectrum of the transmitted signal was analyzed with the
help of an Agilent 86140B laboratory optical spectrum ana-
lyzer. A broadband superluminescent diode was used as an
optical signal source.
As noted above, one of the main problems with the current
type of sensors is the influence of the propagating light’s polari-
zation state on the sensor readings. Even the minimal mechani-
cal deformations of the transmitting fiber can change the
polarization state of the propagating radiation. Our previous
work showed that the use of a polarization-maintaining fiber
(PMF) in combination with a fiber polarizer almost completely
removes the effects of deformation of the supply fiber.24
However, the recording of Bragg structures in PMF is a separate
complex task. In our experiments, we used a compromise ver-
sion of the experimental setup construction. To obtain controlled
and stable polarization after the light source, a fiber polarizer
was also installed, which acts as both the polarizer and the polar-
ization stabilizer in the supply cable. The sensor element was
inscribed in a short section of a standard isotropic fiber spliced
to the fiber polarizer. A laboratory polarization controller was
used to fine-tune the polarization. This setup maintained high
stability of the sensor readings during the experiments. The
setup used in the first experiments is shown in Fig. 3.
Using this setup, the sensitivity of the sensor to the
refractive index of inorganic liquids was investigated. First,
10 ml of distilled water was added to the Petri dish. After
each measurement, 40 ll of isopropanol (0.4% of the original
volume of water) was added to the vessel. The volume con-
centration u of the resulting solution was calculated accord-
ing to the following formula:
0:004  k
u¼ ; (1)
1 þ 0:004  k
where k is the total number of isopropanol additions in the
volume equal to 0.4% of the initial liquid volume. In the
case of mass fraction w, the formula becomes
0:004  k  qi
w¼ ; (2)
1  qw þ 0:004  k  qi
where qi and qw are densities of isopropanol and water corre-
spondingly. The appropriate refraction index changes for the
different concentrations were taken from the literature.26
J. Appl. Phys. 124, 113106 (2018)
FIG. 3. Experimental setup used in the first experiments. 1—broadband
source, 2—sensing element in the test liquid, 3—fiber-polarizer, 4—polari-
zation controller, and OSA—optical spectrum analyzer (Agilent 86410B).
B. Submersible sensor, using the reflected signal
The use of open cells in the form of a Petri dish for car-
rying out experiments is convenient for operative modifica-
tions of the investigated liquid without removal of the
sensor. However, as mentioned above, using open cells has
several disadvantages, which can cause low accuracy of the
experiments. Furthermore, to work with small volumes of
liquids in closed containers, we further modified the setup,
based on scanning the reflected signal from the sensor. This
permits us to avoid the second point of sensor mounting, and
the sensor itself is used as a terminal probe in small contain-
ers. The setup scheme is shown in Fig. 4. A 0.7 ml cylindri-
cal tube was used as a working container for the test
solution. To analyze the spectrum of the sensor, a
MicronOptics sm-125–200 fiber interrogator (1, Fig. 4) was
used instead of a benchtop optical spectrum analyzer. The
interrogator operates with the reflected signal. An integrated
scanning laser is used as an optical signal source. The inter-
rogator has 4 independent optical channels. The plasmon
sensor is connected to one of these channels. Also, we con-
nected a standard Bragg grating to the second one. That grat-
ing was located near the plasmon sensor inside the tube and
was used as a temperature sensor. The configuration of the
supply fiber circuit remained unchanged. As in the previous
version of the installation shown in Fig. 3, in the new modifi-
cation, the fiber polarizer (2) and the laboratory polarization
controller (3) were used (Fig. 4). For unambiguous and
reproducible insertion of the sensor into the small tube, the
latter was equipped with a mechanical motorized positioner
(8) (Fig. 4).
By using an additional Bragg sensor, we were able to
detect the effect of temperature on the plasmon sensor read-
ings and also determine the minimum changes in the liquid’s
refractive index that can be registered by the sensor in this
configuration. It is well known that any medium has refrac-
tive index temperature dispersion. For our sensor, this means
that when the temperature of the investigated liquid changes,
its refractive index will inevitably change, which will affect
the signal spectrum by changing the spectral position of
FIG. 4. Scheme of the second experimental setup with a sensor working on
the reflected signal. 1—four-channel interrogator, 2—fiber-polarizer, 3—
polarization controller, 4—fiber with a plasmon sensor, 5—metal mirror at
the end of the fiber, 6—fiber with a temperature sensor, 7—test tube, and
8—motorized positioner.
113106-4 Tomyshev et al. J. Appl. Phys. 124, 113106 (2018)

plasmon resonance. Since all plasmon sensors somehow

work with a medium having refractive index temperature
dispersion, the most important thing for such sensors is not
its own response to the temperature change but instead that
of the entire sensor-environment system.

C. Sensor for protein detection in solution

The third variant of the setup, the scheme of which is
shown in Fig. 5, is intended to investigate the sensor’s reac-
tion to the adsorption of protein molecules to its surface
from a low-concentration solution. To ensure a uniform con-
centration of the solution near the sensor’s surface through-
out the experiment, the liquid in the tank should be in
constant motion. Such flow can be provided by pumping the
liquid through the cell with the sensor using an external peri-
staltic pump (9), which was implemented in the diagram
shown in Fig. 5. The liquid pumped through the cell was car-
ried out with a tube (10) (Fig. 5). A specially designed cell
(4) was used as capacity containing a channel in which to
install the sensor as well as the input (7) and output branch
pipes (8). The liquid flow was directed along the channel and
the sensor inside it. The optical scheme of the plasmon sen-
sor interrogation was similar to the one shown in Fig. 4.

D. Mathematical processing of experimental data

The usual technique to calculate the spectral position of
plasmon resonance presented in the literature is based on
measuring the intensity of one of the spectral peaks.18,23
However, despite the declared high LOD parameter, such
analysis gives a high probability of error and low reproduc-
ibility under real conditions. We have developed a mathe-
matical apparatus that uses a wide spectral range in the
transmission spectrum of the sensor for complex analysis.
This allowed us to achieve high LOD values, long-term sta-
bility, and high reproducibility of measurements.
An algorithm for automatic processing of initial spectra
was developed for exact and reproducible calculation of the
plasmon resonance’s spectral position. The algorithm of
processing includes two steps: the initial and the main.
The initial step was designed to reduce the impact of
signal deviations of different nature. First of all, the spectrum
goes through a series of frequency filters to remove the high-
frequency noise of the source and receiver. After that, the
average component is calculated and the spectrum is
FIG. 6. Plasmon sensor transmission spectrum before (a) and after (b)
processing.
normalized, thereby the picture becomes aligned with the
abscissa axis. Each of the spectral extrema is additionally
approximated by quadratic functions, which reduces the fluc-
tuations associated with signal noise.
The main step calculates the wavelength of the surface
plasmon resonance The calculation principle is based on the
amplitude of spectral extrema near the plasmon resonance
spectral “constriction.” A smooth continuous curve is con-
structed using a number of the spectral maxima closest to the
constriction (Fig. 6). The curve was optimized with the least-
squares method. The mathematical zero of the derivative of
the resulting curve determined the calculated wavelength of
the plasmon resonance.
As noted above, in detection tasks, it is important to
determine not the absolute value of the plasmon resonance
wavelength but rather the magnitude of its variation under
changing external conditions near the surface of the sensor.
This method of spectra processing together with the stable
optical scheme of the experimental setup made it possible to
achieve high accuracy and reproducibility of the sensor
readings.

FIG. 5. Scheme of the experimental setup for carrying out measurements in

a flow cell. 1—interrogator, 2—fiber polarizer, 3—mechanical polarization
controller, 4—flow cell, 5—sensing element, 6—fiber mirror, 7—liquid flow
input, 8—liquid flow output, 9—peristaltic pump, 10—container with the
investigated liquid, and 11—container with the waste liquid.
IV. RESULTS AND DISCUSSION
The results of measuring the dependence of the sensor
readings on the solution’s refractive index are shown in
Fig. 7.
113106-5 Tomyshev et al.
FIG. 7. SPR wavelength change dependence on the refractive index of the
surrounding liquid.
The refractive index change of the isopropanol solution
in water for each concentration was calculated using formula
(2) and data from the literature. The linearity of refractive
index changes on the isopropanol fraction in the case of low
concentration solutions is confirmed by data from litera-
ture.26 The ordinate shows the change in the plasmon reso-
nance wavelength, the value of which was calculated
automatically from the sensor’s transmission spectrum. The
data were approximated by a straight line, whose slope deter-
mined the sensitivity of the sensor to be 579 nm/RIU (RIU—
refractive index unit), which is well correlated with data
from the literature.8,27–29 The insignificant deviations of the
signal from the straight line are due to the temperature
changes of the sensor and investigated liquid and possible
errors in the solution concentrations.
However, the accuracy, reproducibility, and limit of
detection (LOD) of the sensor cannot be qualitatively evalu-
ated only from an experiment with a solution of alcohol.
Another experiment was carried out to determine these
parameters more precisely. In this experiment, the tempera-
ture dependence of the sensor readings in distilled water was
investigated, using the apparatus described in Sec. III B,
which made it possible to observe changes in the refractive
index through changes in temperature.
In the first stage, the sensor was immersed in a cuvette
with distilled water. The spectra were measured at intervals
of 0.5–3 min for 27 min. The results are shown in Fig. 8. The
time dependence of the calculated spectral position of the
plasmon resonance has a pronounced exponential character,
which, as will be shown below, is related to the temperature
drift during the experiment. Thus, the experimental points
were approximated with a monoexponential curve. At the
same time, the standard deviation of the experimental points
was 9.7  104 nm. Considering the sensitivity of the sensor
to the refractive index of 579 nm/RIU, the standard deviation
of the sensor readings does not exceed 2  106 in terms of
the refractive index, which, corresponds to the resolution of
the sensor or its limit of detection (LOD). This value is
almost an order of magnitude better than the results obtained
J. Appl. Phys. 124, 113106 (2018)
with the known similar sensors.19,27,30 Combining our
approach with the methods of increasing the sensor’s sensi-
tivity31,32 can, ceteris paribus, lead to further improving the
limits of detection.
Nevertheless, a drift in the sensor readings over time
was caused, we assume, by temperature drift and conse-
quently by the drift of the refractive index of water during
the experiment. To verify this assumption, we conducted a
prolonged experiment that involved monitoring the outside
temperature in the room. During the experiment, the temper-
ature in the room changed. The air heated up during daytime,
and cooled at night. The temperature was controlled using a
classical Bragg temperature sensor with a measurement
accuracy of 0.1  C.
For most liquids, the temperature dispersion of the
refractive index is a known parameter. For this reason, accu-
rate measurement of the liquid temperature throughout the
experiment will help to compensate for the thermal fluctua-
tions in the sensor readings. For distilled water at room tem-
perature, the dispersion of the refractive index is of the order
of (1)  104 RIU/ C.30 For many water-based biological
solutions, the temperature dispersion can be considered equal
to water, which makes it possible to use a universal method
for temperature compensation of the sensor readings.
The measured data of the temperature dependence are
shown in Fig. 9. The x-axis represents the time in minutes.
The left y-axis shows the variations in the wavelength of
plasmon resonance (blue curve); the temperature change is
plotted on the right y-axis. The Bragg temperature sensor
readings are shown in the red curve.
According to the temperature sensor at the first stage of
the experiment (area I, Fig. 9), the ambient temperature
increased by 0.3  C, which, in room conditions, should theo-
retically correspond to a decrease in the refractive index of
water by about 3  105.30 In the second stage the tempera-
ture of the investigated liquid decreased by 2.1  C, which
accordingly led to growth in the liquid’s refractive index.
This was observed by the plasmon sensor (area II, Fig. 9). In
the third stage (area III, Fig. 9), air heating in the room was
observed again, and the temperature of the liquid increased
FIG. 8. Experimental data of the plasmon resonance position in water as a
function of time.
113106-6 Tomyshev et al.
FIG. 9. Results of the temperature experiment.
by 1.2  C over the next 3.4 h of the experiment. The changes
in temperature in a room through natural heating and cooling
are obviously exponential, which coincides with the behavior
of the sensor. Thus, we can conclude that the temperature is
the only factor in the changes of plasmon sensor readings.
The temperature dependence of the plasmon resonance posi-
tion is a significant factor to be considered, since both the sil-
ica glass and the investigated liquid have their own
temperature dispersion of the refractive index. This is also
reflected in a small decrease of sensitivity of the sensor in
the temperature experiments, which is consistent with facts
reported in the literature.28,33 In addition, control of the
ambient temperature makes it possible to completely take
into account and compensate for the temperature changes in
the test solution’s refractive index, which can significantly
improve the system’s accuracy as a biosensor.
The sensor’s high resolution to the refractive index
makes it possible to use it as a biosensor. So, for example,
using the apparatus described in Sec. III C, we have mea-
sured different concentrations of myoglobin in a buffer solu-
tion with pH ¼ 5.2. The sensor’s surface was not biologically
modified, so it was not specific to the myoglobin, and all the
measurements were made in pure solutions.
While the solution passes through the cell with the sen-
sor, part of the myoglobin from the solution is deposited on
the sensor surface due to electrostatic interactions, which are
typical for any biological solution. Any material, including
the golden layer on a sensor, will acquire a surface charge,
depending on the solution’s pH.34 The adsorbed protein
changes the average refractive index near the surface of the
sensor, which changes the spectral position of the plasmon
resonance. The adsorption process has a limit that depends
on the coupling properties of the surface with the protein and
is practically independent of the protein concentration in the
solution. In the case of saturation of the adsorption process,
the position of the resonance goes to a new constant level.
This assumption has a completely reasonable physical basis,
if we assume that any of the concentrations under investiga-
tion is sufficiently large to saturate the deposition, which was
confirmed experimentally.
In the simplest approximation, protein deposition on the
sensor surface can be represented in the form of filling a
J. Appl. Phys. 124, 113106 (2018)
finite number of free places on the surface with protein par-
ticles. Since the movement of protein particles in the solution
is rather chaotic, the deposition rate will depend on the num-
ber of occupied places on the sensor’s surface. The number
of filled places dN per time interval from t to t þ dt will be
equal to
N0  N ðtÞ
dN ¼  F  dt ; (3)
N0
where N0 is the total number of places on the sensor’s sur-
face, N(t) is the number of occupied places by time t, and F
is the number of particles incident on the surface per unit of
time, proportional to the concentration of proteins in the
solution C. After a simple transformation
ð ð
dN F
¼ dt: (4)
N0  N N0
Integrating and transforming the result
 
Ft
N ðtÞ ¼ N0 1  e N0 : (5)
Now it becomes obvious that the characteristic time T
when the number of filled places reaches a certain level N1
< N0 will be represented as
const
T¼ : (6)
C
Thus, the characteristic value corresponding to the solu-
tion’s myoglobin concentration in this case is not the abso-
lute value of the sensor response but the time when its
readings reach the maximum level. To test this assumption,
we used various solutions of myoglobin with concentrations
from 50 to 400 ng/ml in glycine buffer. To determine the ini-
tial level of the sensor readings, a pure buffer without the
addition of myoglobin was pumped through the cell with the
sensor. After that, the test solution was injected into the cell.
In the experiment, the time dependence of the sensor read-
ings was recorded.
The experiments carried out in the myoglobin solutions
of different concentrations confirmed the assumption that the
absolute value of the shift in wavelength of the plasmon res-
onance should not be directly used to determine the myoglo-
bin concentration in the solution. Rather, the time when the
curve will reach a new constant level is indicative.
The characteristic response of the sensor to the myo-
globin solution is shown in Fig. 10 using the concentration
of 50 ng/ml as an example. During the first 30 min (area I,
Fig. 10), the sensor reacted to a pure buffer solution; after-
ward, a myoglobin solution was injected into the cell (area
II, Fig. 10). Because of the diffusion processes, the concen-
tration of the solution in the cell increased gradually, which
explains the inconsistency between the initial growth and
formula (4). After that, the curve goes to the quasilinear
section, which we used to establish the speed of the process.
The slope of the curve in this section is sufficiently propor-
tional to the investigated solution’s concentration. At the
end of the experiment, the readings went to saturation, after
113106-7 Tomyshev et al.
FIG. 10. Typical dynamics of the plasmon resonance’s spectral position
change given the flow of myoglobin solution at a concentration of 50 ng/ml.
which a buffer solution was pumped through the cell (area
III, Fig. 10).
Based on the results of the experiments, a calibration
curve was plotted (Fig. 11). The graph represents the depen-
dence of the sensor’s inverted reaction time on the myoglo-
bin concentration. As can be seen from the graph, almost all
the experimental points fit the straight line well, with the
exception of the point corresponding to the highest concen-
tration of the solution, where the sensor’s characteristic
response time is small and comparable to the characteristic
time got mutual diffusion of the test and buffer solutions
inside the cell. As a consequence, the measured sensor
response time was longer than expected, which caused the
calibration curve to deviate from the linear relationship at
concentrations greater than 200 ng/ml. The normal error of
each point shown in the graph became greater as the solution
concentration increases, which was caused by the time of the
above-mentioned mutual diffusion process.
As presented in Fig. 11, the calibration characteristics
make it possible to calculate the myoglobin concentration in
the test solution using the time constant of the dynamics of
the plasmon resonance spectral position change. Such a
FIG. 11. Dependence of the time constant on the myoglobin concentration
in solution.
J. Appl. Phys. 124, 113106 (2018)
system can serve as a basis for further development of sen-
sors with modified surfaces for selective protein detection in
immunoassay systems.
V. CONCLUSION
We have demonstrated an approach to creating highly
stable grating-assisted plasmon fiber sensors by using a
polarizing fiber that polarizes the radiation just behind the
sensitive element. The specialized mathematical apparatus
was used to determine the SPR spectral position change pre-
cisely. The experimental data, based on the detected temper-
ature changes in the refractive index of the investigated
liquid, allowed us to determine the detection limit at the
level of 2  106 RIU. The high resolution of the sensor was
demonstrated in the detection of small protein concentra-
tions, using myoglobin solution as an example, even without
biochemical modification of the sensor surface. The results
obtained are an important achievement toward creating a
highly sensitive fiber SPR sensor for biosensor applications,
particularly for immunoassay devices.
ACKNOWLEDGMENTS
This work was supported by Advanced Research
Foundation.
The authors are grateful to Mrs. Natalia Nechaeva and
Dr. Arkadiy Eremenko from the N.M. Emanuel’ Institute of
Biochemical Physics of RAS for supporting the experiments.
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