U.S. patent application number 14/621641 was filed with the patent office on 2015-07-16 for differential detection for surface plasmon resonance sensor and method.
The applicant listed for this patent is Yeshaiahu Fainman, Lin Pang, Joanna N. Ptasinski, Boris Slutsky, Pang-Chen Sun. Invention is credited to Yeshaiahu Fainman, Lin Pang, Joanna N. Ptasinski, Boris Slutsky, Pang-Chen Sun.
Application Number | 20150198526 14/621641 |
Document ID | / |
Family ID | 52463692 |
Filed Date | 2015-07-16 |
United States Patent
Application |
20150198526 |
Kind Code |
A1 |
Ptasinski; Joanna N. ; et
al. |
July 16, 2015 |
DIFFERENTIAL DETECTION FOR SURFACE PLASMON RESONANCE SENSOR AND
METHOD
Abstract
A differential measurement design employing two nearly collinear
optical beams provides surface plasmon polariton resonance (SPR)
sensors and a corresponding method of increased dynamic range and
signal to noise ratio. The differential measurement device and
method based on wavelength interrogation, employs a single incident
polarization state, and is combined with a 2-D nanohole array for
operation at near-normal incidence, where this approach offers a
decrease in the measurement time.
Inventors: |
Ptasinski; Joanna N.; (La
Jolla, CA) ; Pang; Lin; (San Diego, CA) ; Sun;
Pang-Chen; (San Diego, CA) ; Slutsky; Boris;
(San Diego, CA) ; Fainman; Yeshaiahu; (San Diego,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Ptasinski; Joanna N.
Pang; Lin
Sun; Pang-Chen
Slutsky; Boris
Fainman; Yeshaiahu |
La Jolla
San Diego
San Diego
San Diego
San Diego |
CA
CA
CA
CA
CA |
US
US
US
US
US |
|
|
Family ID: |
52463692 |
Appl. No.: |
14/621641 |
Filed: |
February 13, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13195057 |
Aug 1, 2011 |
8958999 |
|
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14621641 |
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Current U.S.
Class: |
356/445 |
Current CPC
Class: |
G01N 2201/12 20130101;
G01N 2201/06113 20130101; G01N 21/554 20130101 |
International
Class: |
G01N 21/552 20060101
G01N021/552 |
Goverment Interests
FEDERALLY-SPONSORED RESEARCH AND DEVELOPMENT
[0001] This invention (Navy Case NC 103,563) is assigned to the
U.S. Government and is available for licensing for commercial
purposes. Licensing and technical inquiries may be directed to the
Office of Research and Technical Applications, Space and Naval
Warfare Systems Center, Pacific, Code 72120, San Diego, Calif.,
92152; voice (619) 553-5118; email ssc_pac_t2@navy.mil.
Claims
1. In a surface plasmon resonance sensor having a metal-dielectric
interface formed by microfluidic channels integrated with
metal-dielectric layer chips, the method comprising: imaging a pair
of collimated laser beams at different angles of incidence onto
substantially the same spot on a metal nanohole array sample at the
metal-dielectric interface to excite surface plasmons on the array
sample and forming a pair of transmitted laser beams emerging from
the array sample; forming a pair of parallel laser beams
corresponding to the pair of transmitted laser beams; obtaining a
pair of device transfer function (DTF) signals from the pair of
parallel laser beams, where each respective DTF signal has a
different angle of incidence and an intensity peak at a different
wavelength relative to a reference wavelength; calculating a
difference signal from the pair of DTF signals, where the
difference signal has positive and negative values about a zero
crossing axis which are representative of transmittivity relative
to wavelength and where a resulting shift in the location of the
difference signal at the zero crossing axis represents a changing
refractive index of the dielectric at the metal-dielectric
interface.
2. The method of claim 1 where the resonance sensor is in a closed
loop configuration.
3. The method of claim 2 including obtaining the DTF signals at
FWHM (Full Width Half Maximum) values.
4. The method of claim 3 where the array sample is a grating
array.
5. A surface plasmon resonance sensor having a metal-dielectric
interface formed by microfluidic channels integrated with
metal-dielectric layer chips, the sensor comprising: laser means
for generating and imaging a pair of collimated laser beams at
different angles of incidence onto substantially the same spot on a
metal nanohole array sample at the metal-dielectric interface to
excite surface plasmons on the array sample and forming a pair of
transmitted parallel laser beams emerging from the array sample;
processor means for obtaining a pair of device transfer function
(DTF) signals from the pair of parallel laser beams, where each
respective DTF signal has a different angle of incidence and an
intensity peak at a different wavelength relative to a reference
wavelength and for calculating a difference signal from the pair of
DTF signals, where the difference signal has positive and negative
values about a zero crossing axis which are representative of
transmittivity relative to wavelength and where a resulting shift
in the location of the difference signal at the zero crossing axis
represents a changing refractive index of the dielectric at the
metal-dielectric interface.
6. The sensor of claim 5 wherein the sensor operates in a closed
loop configuration.
7. The sensor of claim 5 wherein the processor means obtains the
DTF signals at FWHM (Full Width Half Maximum) values.
8. The sensor of claim 5 where the array sample is a grating
array.
9. The sensor as in claim 8 where the laser means includes a laser
for generating a range of tunable laser beams and beam splitter
means for generating the pair of collimated laser beams.
10. The sensor as in claim 9 including detector means for obtaining
the DTF signals.
11. The sensor as in claim 10 including a computer for calculating
the difference signal.
12. A surface plasmon resonance sensor operating in a closed loop
configuration and having a metal-dielectric interface formed by
microfluidic channels integrated with metal-dielectric layer chips,
the sensor comprising: laser means for generating and imaging a
pair of collimated laser beams at different angles of incidence
onto substantially the same spot on a metal nanohole grating array
sample at the metal-dielectric interface to excite surface plasmons
on the array sample and forming a pair of parallel laser beams
emerging from the array sample; processor means for obtaining a
pair of device transfer function (DTF) signals at FWHM (Full Width
Half Maximum) values from the pair of parallel laser beams, where
each respective DTF signal has a different angle of incidence and
an intensity peak at a different wavelength relative to a reference
wavelength and for calculating a difference signal from the pair of
DTF signals, where the difference signal has positive and negative
values about a zero crossing axis which are representative of
transmittivity relative to wavelength and where a resulting shift
in the location of the difference signal at the zero crossing axis
represents a changing refractive index of the dielectric at the
metal-dielectric interface.
13. The sensor of claim 12 where the processor means includes a
pair of detectors and where the pair of parallel laser beams
impinge on the pair of detectors.
14. The sensor of claim 12 where the pair of collimated laser beams
are transmitted through the grating array sample.
15. The sensor of claim 12 where the pair of collimated laser beams
are reflected from the grating array sample.
16. The sensor of claim 12 including means for detecting the
differential intensity of the pair of parallel laser beams.
Description
BACKGROUND OF THE INVENTION
[0002] The development of disease-related biomarker panels requires
fast and efficient methods for obtaining multi-parameter protein
profiles. Commonly used fluorescent labeling processes are easy to
implement, but they disrupt the accurate measurement of kinetic
constants and can lead to antibody cross-reactivity problems. An
alternative, label-free biodetection method utilizes the phenomenon
of surface plasmon polariton (SPP) resonance. SPP based devices
integrate microfluidic channels with metal-dielectric layer chips,
and measure transmittance or reflectance of light, hereafter
referred to as Device Transfer Function (DTF), at the metal-fluid
interface. The DTF exhibits a sharp resonant feature when the probe
wavelength and the angle of incidence satisfy the condition for SPP
excitation.
SUMMARY OF THE INVENTION
[0003] In one preferred embodiment, the present invention is
related to a method in a surface plasmon resonance sensor having a
metal-dielectric interface formed by microfluidic channels
integrated with metal-dielectric layer chips. In that preferred
embodiment, the method comprises the steps of imaging a pair of
collimated laser beams at different angles of incidence onto
substantially the same spot on a metal nanohole array sample at the
metal-dielectric interface to excite surface plasmons on the array
sample and forming a pair of transmitted laser beams emerging from
the array sample; forming a pair of parallel laser beams
corresponding to the pair of transmitted laser beams; obtaining a
pair of device transfer function (DTF) signals from the pair of
parallel laser beams, where each respective DTF signal has a
different angle of incidence and an intensity peak at a different
wavelength relative to a reference wavelength; and calculating a
difference signal from the pair of DTF signals, where the
difference signal has positive and negative values about a zero
crossing axis which are representative of transmittivity relative
to wavelength and where a resulting shift in the location of the
difference signal at the zero crossing axis represents a changing
refractive index of the dielectric at the metal-dielectric
interface.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] The invention will be more fully described in connection
with the accompanying drawings, where like reference numerals
designate like components, in which:
[0005] FIG. 1a shows a typical SPR scheme to determine the location
of resonance.
[0006] FIG. 1b shows how DTFs are constructed at different angles
of incidence.
[0007] FIG. 1c shows the differential of two DTFs constructed at
different angles of incidence.
[0008] FIG. 2a shows DTF overlap.
[0009] FIG. 2b shows the derivative of the DTF differential.
[0010] FIG. 3 shows illustrations of challenges for DTF
detection.
[0011] FIG. 4a shows a concept block diagram for differential
detection.
[0012] FIG. 4b shows multiplexing duplex channels.
[0013] FIG. 4c shows the difference in the DTFs of the two
channels.
[0014] FIG. 5a and FIG. 5b show the fabrication steps for
fabricating the gated array samples utilized with the present
invention.
[0015] FIG. 6 shows in more detail one of the fabrication steps of
FIG. 5.
[0016] FIG. 7 shows a fluidic chamber mask.
[0017] FIG. 8 shows a block diagram of an experimental setup.
[0018] FIG. 9a shows a time evolution of wavelength relative to
time.
[0019] FIG. 9b shows sensitivity of wavelength relative to
refractive index.
[0020] FIG. 10 shows a differently method of the present invention
for intensity detection.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0021] As has been described above, the development of
disease-related biomarker panels will require fast and efficient
methods for obtaining multiparameter protein profiles. Commonly
used fluorescent labeling processes are easy to implement, but they
disrupt the accurate measurement of kinetic constants and can lead
to antibody cross-reactivity problems. An alternative, label-free
biodetection method utilizes the phenomenon of surface plasmon
polariton (SPP) resonance. SPP based devices integrate microfluidic
channels with metal-dielectric layer chips, and measure
transmittance or reflectance of light, hereafter referred to as
Device Transfer Function (DTF), at the metal-fluid interface. The
DTF exhibits a sharp resonant feature when the probe wavelength and
the angle of incidence satisfy the condition for SPP excitation.
The location of the resonance depends on the refractive index of
the fluid, and therefore informs on its biochemical
composition.
[0022] FIG. 1a shows typical SPR (Surface Plasmon Resonance)
schemes which determine the location of the resonance by monitoring
a shift in point A to A' or monitoring the shift in intensity at a
single wavelength/angle value B to B' or C to C'.
[0023] FIG. 1b shows differential detection in which two DTFs
(DTF1, DTF2) are constructed at different angles of incidence
.alpha.1, .alpha.2. As shown in FIG. 1b, when the refractive index
changes, both DTFs shift in the same direction.
[0024] FIG. 1c shows the differential (DTF1-DTF2) of the two DTFs
constructed at different angles of incidence and the resulting
shift in the differential as a function of changing refractive
index. The differential signal DTF1-DTF2 in FIG. 1c shows the
shifting 5.times. between points D-D' at the zero crossing axis,
where the difference signal is shown as change of transmittivity
(y-axis) relative to wavelength (x-axis).
[0025] The SPP based techniques are broadly classified into
wavelength interrogation, angular interrogation, and intensity
interrogation families. In wavelength (angular) interrogation,
multiple measurements of the DTF are made at different wavelengths
(respectively, angles of incidence), such that the location of the
resonance may be identified by a curve fit (FIG. 1a, shift in point
A to A'). The intensity interrogation method relies on a single
measurement at a fixed angle and wavelength (FIG. 1a, shift in
points B to B' or C to C'). Intensity interrogation devices are
thus simpler than wavelength and angular interrogation devices, but
typically less accurate. This is because changes of the magnitude
and width of the DTF cannot be distinguished from a change in its
location.
[0026] Here we describe a differential intensity interrogation
method, where two measurements of the DTF are made simultaneously
at nearly equal incident angles, and their difference is
constructed (FIG. 1b and FIG. 1c). The zero-crossing of the
difference signal can be tracked with a tunable light source in a
closed-loop system, similarly to the way in which beam position is
tracked using quadrant detectors, resulting in a robust
measurement.
[0027] Closed-loop tracking of the zero crossing is performed
continuously and does not require an end-to-end wavelength sweep
for each measurement. Our device also utilizes a metal film
perforated with a 2-D array of nanoholes, as in Tetz et al. With
this technique, SPP resonance can be achieved at normal or
near-normal incidence, permitting measurement over a large area not
limited by the focal depth of the imaging optics.
[0028] Described initially is a short review of the theory and
concepts associated with plasmonic detection and differential
measurement. Fabrication methods used for the nanohole arrays and
the fluidic chambers are then discussed in full detail. Lastly, our
optical setup, the measurement method and the measurement results
for our differential detection scheme are presented.
[0029] In our plasmonic nanosensor design, the shape of a DTF curve
most closely resembles that of a singly peaked normalized
Lorentzian function, which can be described by:
T L ( .lamda. ) = 1 1 + ( .lamda. - .lamda. 0 1 2 w ) 2 ( 1 )
##EQU00001##
[0030] where .lamda. is the wavelength, .lamda..sub.0 points to the
location where the maximum of the DTF occurs, and w is the
parameter specifying the Full Width at Half Maximum (FWHM). The
centerpoint .lamda..sub.0 and the FWHM w of each DTF excited
through a nanohole array depend on the permittivity of the metal,
the refractive index of the dielectric material, the period of the
grating array, and the angle of incidence.
[0031] The width of the SPR DTF curve (the FWHM of the Lorentzian)
is directly related to the fill factor of the nanohole array, since
a large size hole diameter increases surface wave scattering and
broadens the resonance linewidth.
[0032] Our Rigorous Coupled Wave Analysis (RCWA) simulation results
for a 1D gold nanohole array show a 72% decrease in the FWHM of DTF
when the gold fill factor is increased from 0.5.LAMBDA. to
0.9.LAMBDA.. It should be noted that while small diameter holes
give rise to a narrow FWHM, they are more difficult to fabricate
and they also don't allow for as much light to pass through the
array in the transmission regime ensuing in a lower intensity
signal. In one embodiment, our method of utilizing a
polarizer/analyzer pair enables us to pick up any DTF signal that
may be present and suppress all other light transmission.
[0033] For our experiment we chose the gold fill factor to be 60%
as a trade-off between signal transmission and sharpness of the
DTF. However, other fill factors can also be used, depending on the
desired gain and linear range of the feedback signal and the noise
floor of the detection system.
[0034] For example, an 85% fill yields (according to our RCWA
simulations) 3 times narrower DTFs in FIG. 1(b) than a 60% fill,
and hence 3 times steeper differential slope in FIG. 1(c), but it
would also reduce transmitted intensity by a factor of 2.5.
[0035] Challenges for Device Transfer Function (DTF) Detection are
shown in FIG. 3. Location of the Device Transfer Function (DTF)
allows for the monitoring of surface chemistry
[0036] Traditional DTF detection schemes include: [0037] Signal
peak detection=>low accuracy due to noisy background [0038]
First moment or CoM detection=>high accuracy but time consuming
[0039] Curve fitting=>accurate but even more time consuming
where the acronyms in FIG. 3 are: [0040] DTF--Device Transfer
Function [0041] CoM--Center of Mass [0042] CoCF--Center of Curve
Fit [0043] MSR--Measured Spectral Range [0044] DR--Dynamic
Range
[0045] FIG. 4a shows a conceptual block diagram of the present
invention, FIG. 4b shows multiplexing duplex channels (overlapped
on each other's waist and FIG. 4c shows the difference in the DTFs
of the two channels and the zero crossing detection.
[0046] As noted, wavelength and angular interrogation methods
require multiple measurements of the DTF, which increases
measurement time. Our approach involves just two measurements, one
for each of the two DTFs T.sub.1, T.sub.2, corresponding to
distinct angles of incidence, and the construction of their
difference T.sub.1-T.sub.2. Unlike the individual DTFs, the
difference signal crosses zero (FIG. 1c) and this location of zero
crossing depends only on the locations of the DTFs and not on their
magnitude and width. Instead of measuring at the point of maximum
signal strength from a DTF curve (i.e., A.fwdarw.A' in FIG. 1a),
measure the points that are most sensitive with respect to change
of the DTF (i.e., C.fwdarw.C' and B.fwdarw.B' in FIG. 1a). The
difference signal has a greater linear range than the individual
DTFs, as seen in FIG. 1c and FIG. 4c. Both these features are
advantageous in a measurement system that tracks the zero crossing
with a closed-loop controller, as shown in FIG. 4a.
[0047] The closed-loop configuration shown in FIG. 4a includes a
laser means for imaging a pair of laser beams onto a nanohole array
to excite surface plasmon resonance and form a pair of transmitted
laser beam emerging from the nanohole array. The laser means then
forms a pair of transmitted parallel laser beams emerging from the
nanohole array which impinge on a pair of detectors (detector A and
detector B). A processor means obtains a pair of device transfer
function (DTF) signals from the pair of parallel laser beams, where
each respective DTF signal has a different angle of incidence and
an intensity peak at a different wavelength relative to a reference
wavelength. The processor means calculates a difference signal from
the pair of DTF signals, where the difference signal has positive
and negative values about a zero crossing axis which are
representative of transmittivity relative to wavelength and where a
resulting shift in the location of the difference signal at the
zero crossing axis represents a changing refractive index of the
dielectric at the metal-dielectric interface.
[0048] As will become apparent, advantages of the present invention
are: [0049] Only two data points required [0050] Immune to the
power fluctuation of source since it impacts both DTFs equally
[0051] Reduction of some systematic errors [0052] Suitable for
feedback loop devices
[0053] When the two Lorentzians T.sub.1, T.sub.2 are centered
respectively at wavelengths .lamda..sub.1, .lamda..sub.2 the slope
.differential.(T.sub.1-T.sub.2)/.differential..lamda., which is a
measure of the linear region of the difference between two DTFs, is
expressed as
T D ' ( .lamda. ) .lamda. 1 - .lamda. 2 = .differential.
.differential. .lamda. [ ( 1 + ( .lamda. - .lamda. 1 1 2 w ) 2 ) -
1 - ( 1 + ( .lamda. - .lamda. 2 1 2 w ) 2 ) - 1 ] ( 2 )
##EQU00002##
[0054] This slope is plotted in FIG. 2 for various separations
between the center of T.sub.1 and T.sub.2. In a closed-loop control
system, a steep slope improves measurement sensitivity, while a
wider linear region is desirable to make the controller more
robust. FIG. 2 illustrates the tradeoff between these two
parameters. In the present work, we chose
.lamda..sub.1-.lamda..sub.2=FWHM as a reasonable compromise.
[0055] Differential detectors have long been utilized in confocal
microscopy, range finding, etc. An advantage of differential
measurement is the unique property of self-referencing for optical
source fluctuation, since any fluctuation of the intensity will
impact the adjacent DTFs equally and thus cancel itself. This
concept has been widely adapted by the telecommunication industry,
where differential signals are used to carry the bits that
eliminate the cause of "ground" noise.
[0056] FIG. 2a shows the DTF overlap of intensity relative to
wavelength and FIG. 2b shows the derivative of the DTF
differential, T.sub.D=T(.lamda..sub.1)-T(.lamda..sub.2), when the
DTF curves are overlapped at the 0.5 transmittivity value (solid
curve), 0.75 value (dashed curve), and the 0.34 point (dotted
curve).
[0057] As shown in FIGS. 5a and 5b, the samples (one of which is
also shown in FIG. 9) were fabricated using holographic lithography
where two interfering UV laser beams were incident upon negative
MicroChem SU8 photoresist placed on top of a 1.2 mm thick SiO.sub.2
substrate. In order to achieve a hole pattern, each sample was
exposed and then rotated 90.degree. for an additional exposure
step. Prior to the exposure, the SiO.sub.2 substrate was cleaned in
a Pirahna bath (1:1:5 of H.sub.2O:H.sub.2O.sub.2:H.sub.2SO.sub.4)
solution for 30 minutes and the surface was dehydrated by baking on
a hot plate at 200.degree. C. for 5 minutes. A 2 .mu.m layer of
SU8-5 was spin deposited at 3000 rpm. The samples were exposed (as
shown in FIG. 6) with a Coherent Innova 300 Argon-Ion laser
centered at 364 nm with a 150 mJ dosage per exposure, and followed
by a convection oven soft bake for 1 minute.
[0058] The SU8 development time was 3 minutes and it was followed
by an IPA rinse. A 5 nm thick Titanium adhesion layer, followed by
a 100 nm gold layer was sputtered onto the samples using the Denton
Discovery 18 Sputter System. Fluidic chambers made of
Polydimethylsiloxane (PDMS) were affixed on top of each sample's
grating array using oxygen plasma. It should be noted that PDMS
does not readily bond to Au, hence a region of bare SiO.sub.2 was
left on each sample, surrounding the 4 cm.sup.2 gold grating array,
in order to facilitate in the PDMS adhesion. The main portion of
the fluidic chamber was 13 mm by 2 mm in size, allowing for both
beams to be easily directed onto the grating portion of the sample.
The fluidic chamber mask is shown in FIG. 7, with the main portion
of the chamber having dimensions of 13 mm by 2 mm in size, as
shown.
[0059] The grating array sample shown in FIG. 5a has a 1400 nm
period with 600 cm hole diameter and 1 cm.sup.2 area. The hole size
is significant for FWHM of the DTF.
[0060] FIG. 8 shows an experimental setup 50 used to measure SPR
response to different concentration ethylene glycol solutions. The
setup shown in FIG. 8 consists of a tunable New Focus laser 52 in a
range of 1520 nm-1570 nm connected to a polarization scrambler 54
in order to randomize the polarization state of input light and to
minimize polarization dependent loss associated with the components
of the experimental setup. In order to perform the differential
measurement, the collimated beams incident at different angles need
to meet at the same spot on the sample 60 shown in FIG. 8.
[0061] This is accomplished by using two polarization independent
beam splitters positioned in a Mach-Zehnder configuration 56, where
two beams separated by the first splitter are multiplexed at the
same spot onto the second splitter; then both beams from the second
splitter are imaged with a 4-F telecentric imaging system 58 on to
the sample surface 60, where the relative angle between the two
beams can be fine adjusted by rotation of the second beam splitter.
Equal beam path lengths ensured spots from the two beams to be
equal sized. Light emerging from the sample 60 is then spatially
Fourier transformed by a lens 64 into two parallel beams, where
each one is receipted by a photodetector for the differential
measurement.
[0062] In lieu of a pair of detectors, we used an Indigo Merlin CCD
camera 68 to record light from the two beams and thus obtain the
DTFs corresponding to the two angles of incidence at the sample.
The differential signal was then calculated by the computer 70. A
pair of polarizers was placed with one element in front and one
element behind the sample, where their polarization state was set
to a cross position, to suppress directly transmitted light
(nonresonant transmission) and isolate the observation of SPP
resonance. The sample along with the microfluidic delivery system
was mounted on a rotational stage.
[0063] Prior to measurement, the laser wavelength was set to 1545
nm and the sample was rotated to obtain equal power in the two
detectors. In this way, .lamda.=1545 nm was positioned midway
between the maxima of the two DTFs at the zero-crossing of the
differential signal (see FIG. 1c and FIG. 4c).
[0064] The detector output was then monitored while fluids of
varying refractive indices were introduced into the fluidic
channel. Before a measurement was performed, methanol was advanced
into the PDMS chamber in order to clean the sample. H.sub.2O was
used to flush the methanol and various concentrations of an
ethylene glycol solution, ranging from 1.9% to 9.1%, were
introduced into the chamber. The measurement process was automated
via a Labview program with a GPIB interface 74 to the New Focus
tunable laser 52 and video grabbing card to the CCD 68.
[0065] FIG. 9 reports the results of an experiment in which six
different ethylene glycol/water solutions (abbreviated "sln") were
sequentially introduced into the fluidic chamber. The refractive
indices of the solutions, measured separately with a refractometer,
are indicated in the inset in FIG. 9a.
[0066] Throughout the test, the laser wavelength was continuously
adjusted to track the zero-crossing of the differential signal by
maintaining equal power in the two detectors. The zero-crossing
wavelength is plotted in FIG. 9a as a function of time, and in FIG.
9b as a function of the refractive index of the fluid.
[0067] From the linear curve fit in FIG. 9b the sensitivity figure
S.sub..lamda..ident.d.lamda./dn=1390 nm/RIU. This is consistent
with the analytical expression given by Pang et al. for plasmonic
mode (1,0) and grating period close to 1400 nm.
[0068] The evolution of the SPP differential detection spectral
response is shown in FIG. 9 as a function of time, in which FIG.
9(a) shows different concentrations of ethylene glycol are
introduced at various time intervals, and FIG. 9(b) shows a linear
fit of the time evolution measurement, where the sensitivity
(response to index variation) is represented by the slope. In this
case the sensitivity is 1390 nm/RIU, and the grating period is 1400
nm. The y-axis in FIG. 9b represents A-B zero crossing in
wavelength and the x-axis represents the refractive index.
[0069] We have presented a differential measurement technique for a
nanoplasmonic sensor operating in the transmission regime. The
differential technique provides a two fold increase in the dynamic
range of intensity due to the contribution of the second DTF, it
decreases the measurement time due to the tracking of just the zero
crossing point, in addition to extending the dynamic range and
signal to noise ratio. The differential DTF intensity measurement
can be amplified by controlling the resonance FWHM, where a
narrower FWHM translates into a steeper differential slope. We
bypassed the cumbersome Center of Mass (CoM) and only used
smoothing for our experiment, where we achieved detection
resolution on the order of 10.sup.-5 RIU. The sensitivity can be
improved by increasing the fill factor of the nanohole array at the
expense of a reduction in the signal level.
[0070] From the above description of the surface plasmon resonance
sensor and method, it is apparent that various techniques may be
used for implementing the concepts of the present invention without
departing from its scope.
[0071] For example, we can also use our differential method for
intensity detection. In this scenario as shown in FIG. 10, after we
calibrate the system, we position ourselves at a single wavelength
corresponding to the zero crossing of our calibration differential
(middle curve 84 as shown in FIG. 10 and corresponding to an index
of n=1.3373). Then as the solution/gas formulation is replaced by a
different one (and thus the corresponding refractive index changes
as shown by left curve 82, with an index of n=1.3354, or right
curve 86 with n=1.3395 in FIG. 10), we just monitor the change in
intensity. With our differential detection method the range of
measureable intensity is doubled.
[0072] For the differential intensity detection, the slope of the
differential curve determines the sensitivity. A very steep slope
directly translates into higher sensitivity.
[0073] Also, the differential detection method can also be set up
and used in reflection mode, where the closed-loop configuration
shown in FIG. 4a includes a laser means for imaging a pair of laser
beams onto a nanohole array to excite surface plasmon resonance and
form a pair of reflected laser beam emerging from the nanohole
array. The laser means then forms a pair of reflected parallel
laser beams emerging from the nanohole array which impinge on a
pair of detectors.
[0074] In one preferred embodiment, a surface plasmon resonance
sensor is described, having a metal-dielectric interface formed by
microfluidic channels integrated with metal-dielectric layer chips.
One preferred method includes the steps of imaging a pair of
collimated laser beams at different angles of incidence onto
substantially the same spot on a metal nanohole array sample at the
metal-dielectric interface to excite surface plasmons on the array
sample and forming a pair of transmitted laser beams emerging from
the array sample; forming a pair of parallel laser beams
corresponding to the pair of transmitted laser beams; obtaining a
pair of device transfer function (DTF) signals from the pair of
parallel laser beams, where each respective DTF signal has a
different angle of incidence and an intensity peak at a different
wavelength relative to a reference wavelength; and calculating a
difference signal from the pair of DTF signals, where the
difference signal has positive and negative values about a zero
crossing axis which are representative of transmittivity relative
to wavelength and where a resulting shift in the location of the
difference signal at the zero crossing axis represents a changing
refractive index of the dielectric at the metal-dielectric
interface.
[0075] The described embodiments are to be considered in all
respects as illustrative and not restrictive. It should also be
understood that the surface plasmon resonance sensor and
corresponding method is not limited to the particular embodiments
described herein, but is capable of many embodiments without
departing from the scope of the claims.
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