U.S. patent application number 10/647229 was filed with the patent office on 2005-03-03 for repeated structure of nanometer thin films with symmetric or asymmetric configuration for spr signal modulation.
Invention is credited to Chang, Peizen, Huang, Chen Kung, Lee, Chih Kung, Lee, Shu Sheng, Lin, Chii-Wann, Lin, Shiming.
Application Number | 20050045977 10/647229 |
Document ID | / |
Family ID | 34216485 |
Filed Date | 2005-03-03 |
United States Patent
Application |
20050045977 |
Kind Code |
A1 |
Lin, Chii-Wann ; et
al. |
March 3, 2005 |
REPEATED STRUCTURE OF NANOMETER THIN FILMS WITH SYMMETRIC OR
ASYMMETRIC CONFIGURATION FOR SPR SIGNAL MODULATION
Abstract
A symmetric or asymmetric multilayer structure based on the
technique of surface plasmon resonance (SPR) has been applied for
modulation of resonant angle and wavelength. The fabrication of
this invention can have nanoscale thin film layers up to several
hundreds, while each layer has its own material of a high or low
refractive index value, and the total layers in a thickness of tens
to hundreds nanometers are grown in this single structure. This
invention is intended for optimizing the scanning of mechanism by
modulating SPR resonant angle and wavelength, and for developing
the prospect of portable instruments.
Inventors: |
Lin, Chii-Wann; (Taipei
City, TW) ; Huang, Chen Kung; (Taipei City, TW)
; Lin, Shiming; (Taipei City, TW) ; Lee, Chih
Kung; (Taipei City, TW) ; Chang, Peizen;
(Taipei City, TW) ; Lee, Shu Sheng; (Taipei City,
TW) |
Correspondence
Address: |
RABIN & BERDO, P.C.
Suite 500
1101 14th Street, N.W.
Washington
DC
20005
US
|
Family ID: |
34216485 |
Appl. No.: |
10/647229 |
Filed: |
August 26, 2003 |
Current U.S.
Class: |
257/428 |
Current CPC
Class: |
B82Y 20/00 20130101;
Y10S 977/719 20130101; G01N 2021/757 20130101; G01N 2021/7776
20130101; Y10S 977/792 20130101; G01N 21/553 20130101; G01N 21/554
20130101; G02B 6/1226 20130101; Y10S 977/759 20130101 |
Class at
Publication: |
257/428 |
International
Class: |
H01L 033/00 |
Claims
What is claimed is:
1. An active surface plasmon resonance (SPR) chip, comprising: a
first layer of metal; an outmost layer of metal; and a nanometer
multilayer structure having a high refractive index of material and
a low refractive index of material to form at least a monolayer
structure interposed between said first layer of material and said
outmost layer of material such that resonant angle and wavelength
occurs through an arrangement of said nanometer multilayer
structure.
2. An active SPR chip as recited in claim 1, wherein said first
layer of material and said outmost layer of metal can be a same
material, thereby presenting a symmetry structure.
3. An active SPR chip as recited in claim 1, wherein said first
layer of material and said outmost layer of metal can be a
different material, thereby presenting an asymmetry structure.
4. An active SPR chip as recited in claim 1, wherein said active
SPR chip adopts Sputter as a first method for developing thin film
deposition.
5. An active SPR chip as recited in claim 1, wherein said active
SPR chip adopts CVD as a second method for developing said thin
film deposition.
6. An active SPR chip as recited in claim 1, wherein said active
SPR chip adopts MBE as a third method for developing said thin film
deposition.
7. An active SPR chip as recited in claim 1, wherein said active
SPR chip adopts a partial method of VCSEL for developing.
8. An active SPR chip as recited in claim 1, wherein said active
SPR chip adopts MicroElectroMechanical process technique as a
method for fabrication.
9. An active SPR chip as recited in claim 1, wherein each layer in
a plurality of layers of said nanometer multilayer structure has a
thickness of 10 up to 1,000 nanometers.
10. An active SPR chip as recited in claim 1, wherein said
nanometer multilayer structure is composed of a plurality of pairs
of materials, said pair being formed by said high refractive index
of material and said low refractive index of material, and number
of said pairs can be from 1 up to tens.
11. An active SPR chip as recited in claim 1, wherein a total of a
plurality of said layers in said nanometer multilayer structure has
a thickness no more than 900 nanometers.
12. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is Zinc Sulfide.
13. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is Magnesium Fluoride.
14. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is GaN.
15. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is ITO.
16. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is ZnTe.
17. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is BeZnTe.
18. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is MgSe/BeZnTe.
19. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is InGaAs.
20. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is InP.
21. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is GaAs.
22. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is Al.sub.xGa.sub.1-xAs.
23. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is GaAsSb.
24. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material is Al.sub.xGa.sub.1-xN.
25. An active SPR chip as recited in claim 1, wherein said high
refractive index of material and said low refractive index of
material forms different metallic-dielectric boundary.
26. An active SPR chip as recited in claim 1, wherein said first
layer of material couples to crystal or glass substrate.
27. An active SPR chip as recited in claim 1, wherein said first
layer of material is coated with binding biomolecules.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to the research of a
biomedical chip in sensing protein biomolecules by an optical
method and more particularly relates to a procedure of coating a
metal film on a surface plasmon resonance (SPR) device and a novel
design of a multilayer structure.
BACKGROUND OF THE INVENTION
[0002] Disregard the fact that quite a few patents on genetic
engineering related techniques have raised many legal and ethical
issues, human beings have indeed made a big progress in knowing
their own origin during the last century. A widely recognized
discovery is the rough draft of the human genome, or the molecular
sequence of DNA that comprises the human genes. A biochip, known as
DNA microarrays, was designed in the late of last century for
accelerating genetic research. This new technology is expected to
detect the presence of a whole array of genetically based diseases,
and, moreover, to conduct widespread disease screening.
[0003] A combination of molecular biology and micro-fabrication
techniques has been applied to produce miniature analytical
devices. This miniature analytical device is called a "biochip",
and its device wafer is composed of glass, plastic, or silicon. The
miniature analytical device also enables on-chip reactions and
assays, which reduces volumes of reagents and raises density. Due
to the variety of biochemical assays, reagents such as DNA probes,
enzymes, antibodies or protein, are adhered to the surface of a
biochip for various applications. Biochips are expected to
revolutionize biology in the same way electronic chips
revolutionized electronics.
[0004] Biochips will consistently grow smaller and more powerful
with each new generation of biochip created. Additionally, the
development of specialty biochips, made from various organic
materials, can lead to new developments and utilizations. One
encouraging development is the protein-based biochips. These
biochips would be used to array protein substrates for drug lead
screening, antibodies for diagnostic purposes, where the biochip
then is also a biosensor, enzymes for catalytic reaction analysis
and other applications. The basic construction of protein chips has
some similarities to DNA chips, such as the use of a glass or
plastic surface dotted with an array of molecules. These molecules
can be DNA or antibodies that are designed to capture proteins.
Protein microarrays are being used as powerful tools in
high-throughput proteomics and drug discovery. Most of the current
protein chips are based on the reactions between the capture
proteins immobilized on a surface and the analyte proteins in the
sample solution. A recent example of this technology shows, some
Chinese scientists from laboratories announced they have invented a
protein chip, which can rapidly diagnose severe acute respiratory
syndrome (SARS). With the protein chip, doctors can tell SARS
carriers from the suspects, as well as promptly monitor the latest
development of the virus.
[0005] Although the DNA-chip marketplace is in its infancy, with
considerable challenges remaining to be overcome, some techniques:
DNA composition analysis, determination of a DNA sequence and
quantitative analysis, capillary electrophoresis, nucleic acid
amplification test, and gene expression analysis are progressing
toward maturity. Furthermore, a series of other analytical methods,
as a result of the mentioned techniques: cell separation, and
cell-mediated immunity analysis are combined with combinatorial
chemistry to feature a massive flux aspect while engaging the
primitive screening for new medicine. The materials that are
available presently for producing biochips include plastic film
form technology, elastomer, and silicon. The focus of the biochips
development in the field lately is on DNA applications which
deserve an extra attention from us. A series of technology and
product development are induced, subject to the requirements of
DNA's sensing. For instance, prompt sensing and analytical
techniques and products, DNA replication and splicing analysis
techniques and products, and integrated DNA analytical systems.
[0006] Surface plasmon resonance (SPR) is a quantum
optical-electrical phenomenon arising from the interaction of light
with a metal surface. The energy carried by photons of light is
transferred to packets of electrons, called plasmon, on a surface
of metal under certain conditions. Energy transfer occurs only at a
specific resonance wavelength of light, which is an effect of
equivalence in quantum energy of both the plasmon and photons. A
surface plasmon sensor includes a dielectric block, a metal film
which is formed on one face of the dielectric block and is brought
into contact with the sample, a light source and an optical system
which causes the light beam to enter the dielectric block and
converges the light beam on the interface of the dielectric block
and the metal film so that components of the light beam impinge
upon the interface at various angles including angles of total
reflection.
[0007] At certain wavelengths of incident light and angles, part of
the incident light resonate across the metal and sample boundary,
producing attenuation of the reflected signal--the surface plasmon
resonance effect. This effectively corresponds to a change in
refractive index at the surface. The magnitude of the effect
depends upon the wavelength of the incident light, the angle of
incidence, the mass density of the species adhered to the metal
surface, and the refractive index and dielectric constant of the
sample layer. The binding of the reagent and the analyte attached
to the metal surface produces a change in the mass density on the
metal surface, which as a result of the surface plasmon resonance
effect, produces attenuation of the reflected signal.
[0008] Among the technologies on chip development, the optical
methods for sensing are better choices for their sensitivity and
resolution. Although fluorescence type gains many applications,
surface plasmon resonance (SPR), as a research tool, has shown its
advantages in quantifying pair of molecules interaction including:
measurements are made in real-time and in situ, no labeling of
either antibody or antigen molecules. Conventionally, biomolecular
interactions are studied using techniques as immunoassays (ELISA or
RIA), equilibrium dialysis, affinity chromatography and
spectroscopy.
[0009] As a result, the SPR angle will change according to the
amount of binding molecules. There is a linear relationship between
the amount of binding molecules and the shift of the SPR angle. The
SPR angle shifts in millidegrees as a response to quantify the
binding of macromolecules to the sensor surface. A change of
hundred millidegrees represents a change in surface protein
coverage of approximately 1 ng/mm.sup.2, or in bulk refractive
index of approximately 10.sup.-3. The detection principle and
penetration depth of the evanescent wave, 300-400 nm, limit the
size of analyte to be measured. Macromolecules cannot be sensed in
full size if it is wider than about 400 nm; consequently, the
linear relationship is no longer valid. A qualitative analysis
will, under these circumstances, take the place of the quantitative
or kinetic analysis.
SUMMARY OF THE INVENTION
[0010] An object of the present invention is to achieve modulation
of resonant angle and wavelength by utilizing the SPR principle
through a symmetrical or asymmetrical multilayer structure in the
Z-axis direction. The fabrication of this invention can have
nanoscale thin film layers up to several hundreds, while each layer
has its own material of a high or low refraction index value, and
the total layers in a thickness of tens to hundreds nanometers are
grown in this single structure.
[0011] Another object of the present invention is to apply this
symmetrical or asymmetrical multilayer structure and an optical
modulator to the design of SPR based chips and applications.
[0012] A further object of the invention is to apply this
symmetrical or asymmetrical multilayer structure and an optical
modulator to the design of disposable protein biosensing chips.
[0013] The present invention offers a novel construction of
dielectric coupler, which substantially reduces the drawbacks of
the existing devices, while tremendously improves the efficiency of
the angular interrogation of mechanism and wavelength interrogation
applications. With regard to the sensing of common SPR chips, the
resonant angle after coated with a metal layer is usually about 74
deg in air, while 87 deg in liquid, which is difficult in
calibration and measurement with scanning mechanism and
inconvenient to use. The multilayer structure of this present
invention enables a square-wave grating coupler based SPR system,
through the adjustment of refractive index and thickness of the
material, the resonance of wavelength and angular can be
achieved.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The invention can be more fully understood by reading the
following detailed description of the preferred embodiments, with
reference made to the accompanying drawings, wherein:
[0015] FIG. 1 is a schematic view of the present invention;
[0016] FIG. 2 is an illustrative front view of an array-based
active SPR chip of the present invention;
[0017] FIG. 3 is an illustrative bottom view of an array-based
active SPR chip;
[0018] FIG. 4 shows resonant wavelength with regard to reflective
ratio in modulated angle with water sample;
[0019] FIG. 5 shows resonant wavelength with regard to reflective
ratio in modulated wavelength with water sample;
[0020] FIG. 6 shows resonant angle with regard to reflective ratio
in modulated angle with water and alcohol sample;
[0021] FIG. 7 shows resonant angle with regard to reflective ratio
in modulated wavelength with water and alcohol sample;
[0022] FIG. 8 shows resonant wavelength with regard to reflective
ratio in modulated angle with water and alcohol sample; and
[0023] FIG. 9 shows resonant wavelength with regard to reflective
ratio in modulated wavelength with water and alcohol sample.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Embodiments of the present invention will now be described
through a symmetric or asymmetric multilayer structure in an active
surface plasmon resonance (SPR) chip, with reference to the
accompanying figures. Referring first to FIG. 1, a symmetric or
asymmetric multilayer structure in an active surface plasmon
resonance (SPR) chip comprising: a prism 1, a substrate material 2,
a thin gold film (can be other metal film) 3, a nanometer
multilayer dielectric thin films 4, and a thin gold film 5.
[0025] The interposed stack of nanometer multilayer thin films is
organized by the materials of a high and low refractive index
alternately, and the thickness of each layer is set a fraction of
wavelength of the incident light, which is about a tens to several
hundreds of nanometers. Number of total layers is dependent on the
equivalent refractive index as that in a single dielectric
layer.
[0026] Material of a high or low refractive index can be viewed as
a constituent of a "pair", and a few pairs to tens of pairs in
general are the whole. A modulated resonance of angle and
wavelength is subject to the equivalence of desired refractive
index formed by the multiple layers, while the thickness of the
total layers is no less than about nine hundred nanometers.
Materials of high and low refractive indices are made of following
compounds: ZnS, MgF, GaN, ITO, ZnTe, BeZnTe, MgSe/BeZnTe, InGaAs,
InP, GaAs, Al.sub.xGa.sub.1-xAs, GaAsSb, Al.sub.xGa.sub.1-xN and
the like. Desired materials also include the coupling of metal
(gold, silver) and dielectric layer. A biochip can be fabricated by
a nanometer multilayer thin films structure thereto coupling to
glass or crystal substrate, and is coated with binding biomolecules
or other reagents on the metal surface.
[0027] For purpose of illustration, the interposed nanometer thin
films of the present invention, like the multilayer dielectric
stack of the prior art, is shown in FIG. 1 as comprised of eight
layers. Actually, the first preferable embodiment as the result
shown in FIGS. 4 and 5 has six interposed layers,
Prism/L/H/L/H/L/H/Au/Sample, of dielectric thin films in the
overall chip structure for water sample, while the second
preferable embodiment as shown in FIG. 6 through 9 has eight layers
of dielectric thin films as a modification from the first
embodiment, Prism/L/H/L/H/L/H/Au/Sample, in the overall chip
structure for water and alcohol sample.
[0028] The observed resonant wavelengths with regard to a set of
reflective ratios obtained by way of angular and wavelength
interrogations respectively are shown in the FIGS. 4 and 5, the
resonant conditions of these two experiments are further recognized
as the consequence of the attenuate total reflection (ATR)
principle. Within the first preferred embodiment, the setup for the
two experiments includes 65 degrees as the incident angle of light
and 1.33 as the refractive index of water.
[0029] The analytical sample within the second preferred embodiment
utilizes water and alcohol, which is used for the following four
experiments under the same configuration as that in the first
preferred embodiment, and the experimental results will be shown in
FIG. 6 through 9.
[0030] Experiments shown by FIGS. 6 and 7 are focused on the
resonant angles with regard to a set of reflective ratios obtained
by angular and wavelength interrogations respectively, and the
setup for the two experiments includes a 632.8 nm as wavelength of
incident light and 1.33 and 1.3652 as the refractive indices of
water and alcohol respectively. Resonant wavelengths are the
desired object in FIGS. 8 and 9, the setup for the two experiments
includes 65 degrees as the incident angle of light and 1.33 and
1.3652 as the refractive indices of water and alcohol
respectively.
[0031] According to the comparison between the preferred
embodiments thereto and the traditional metal coated SPR chip, the
embodiments based on angular modulation technique substantially
raise the performance such as: resonant angle changes up to 10 deg.
(from 70 down to 60), resonant amplitude alters about 20 times, and
as a consequence, the signal to noise ratio improves 180 times.
Furthermore, the embodiments based on wavelength modulation
technique substantially raise the performance such as: resonant
wavelength changes up to 130 nm (from NIR down to VIS), FWHM alters
about 3 times, and as a consequence, capable to offer narrower
bandwidth of spectrum for visual sensing applications, and support
multi-wavelength modules in engaging multi-channel efficiency
verification.
* * * * *