Optics: measuring and testing – Of light reflection
Reexamination Certificate
2000-07-17
2003-07-29
Epps, Georgia (Department: 2873)
Optics: measuring and testing
Of light reflection
C356S446000
Reexamination Certificate
active
06600563
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to optical resonance analysis systems, specifically to certain sensor design aspects and to analysis systems comprising illumination and detection systems that utilize those sensors for analysis
BACKGROUND OF THE INVENTION
Because of the recent surge in applications, sensor based instruments are becoming very popular. This growth in applications has been primarily spurred by the biotechnology and the pharmaceutical industries especially from the enormous influx of information from the Human Genome Program. This drove of information has resulted in a corresponding spawning of new industries. Some of the newest, rapidly growing industries are: proteomics, where proteins, function and genomics come together; and pharmacokinetics where researchers attempt to find products of combinatorial synthesis that have binding properties to unique sites such as receptors, that typically result in a biological altering event. Both technologies rely on assays to be robust and process thousands of samples/day. It is obvious that handling this amount of material at these speeds would benefit from automated processes and miniaturization. One very popular application such as monitoring DNA/DNA, DNA/RNA, RNA/RNA hybridization has always been important, but as genes are discovered and associated with disease states, genetic analysis in diagnostics requiring hybridization assays becomes a necessity. However, to obtain the information to determine the genetically relevant data, thousands of tests need to be run on one sample if conventional technologies are used. New developments in sensor technology can reduce this analysis time from weeks to hours.
Sensors can be described as being composed of two parts; the transducer and the active site. The transducer is defined as the part of the device that is capable of reporting change in its environment. Transducers can operate in several different modes but the most common are optical based devices. Examples of optical based transducers include surface plasmon resonance (SPR) devices and planar waveguide devices and grating coupled waveguide devices. These types of sensors are described in U.S. Pat. Nos. 4,882,288, 4931,384, 4,992,385, and 5,118,608 all incorporated by reference. The sensor may consist of a single analysis site, a one dimensional or linear array of analysis sites or a two dimensional array of analysis sites.
Surface Plasmon Resonance Devices
Surface plasmon, which exists at the boundary between metal and dielectric, represents a mode of surface charge vibrations. The surface charge vibration is the vibration of the electrons on the metal surface generated by exterior light, these electrons behaving like free electrons. The surface plasmon wave extends into space or dielectrics as an evanescent wave and travels along the surface. The plasmon field satisfies the Maxwell equations and boundary conditions for p-polarized radiation. This boundary condition requires that the dielectric constants of metal and dielectrics have opposite sign. Since the common dielectric compound has a positive dielectric constant, the plasmon exists in the frequency region of the metal where the dielectric constant is negative. This situation happens at a frequency of the exterior light and lower frequencies, in which the real part of the refractive index of the metal is equal to or smaller than its imaginary part. For instance, for metals such as Gold, Silver or Aluminum, this frequency, the plasmon frequency, is about 5, 4 or 15 eV, respectively, resulting in a plasmon wave being available in a frequency range covering WV, Visible and Infrared regions. In this frequency range, since the wave vector of the surface plasmon is larger than that of the exterior light, the exterior light cannot interact directly with surface plasmon.
Utilization of the surface plasmon becomes possible when the exterior light wave is coupled with the surface plasmon by means of a grating or prism. These optical components provide an additional wave vector component to the exterior light, enabling energy exchange between the exterior light and the surface plasmon. The plasmon on the metal grating can interact with the exterior light by picking up an additional transverse momentum defined by the period of the structure.
On the other hand (as in the back illuminated Kretchman design), attenuated total reflection in a high refractive index material such as a prism provides additional transverse momentum so that the exterior wave has a wave vector larger than the vacuum wave vector, and the wave vector in the prism is large enough to match to the plasmon wave vector.
The prism method has been frequently utilized to determine optical constants of metals, because the resonance condition changes by the change in the refractive index. As gratings play an important role in promoting the surface plasmon, this in turn means that the surface plasmon causes some anomalies to grating performance. Because of the phenomena, theory of surface plasmons was also developed by grating scientists.
The SPR type device basically measures refractive index changes in a thin 1 &mgr;m evanescent field zone at its surface. The active surface defines the application and the specificity of the transducer. Various types of surface modifications can be used, for example, polymer coated transducers can be used to measure volatile organic compounds, bound proteins can be used to look for trace amounts of pesticides or other interactive molecules, DNA can be used to look for the presence of complementary DNA or even compounds that bind unique DNA sites. Specific sensors can be obtained by generating arrays of specific DNA sequences that hybridize the sample DNA. This technique is commonly referred to as array hybridization.
This type of sensor can operate in a gas or a liquid environment, as long as its performance is not degraded. Temperature range is selected by the application and should be controlled to better than 0.1° C. for maximum sensitivity measurements.
Arrays have been built using fluorescence as the reporter but technologies such as SPR may be used resulting in reduced hardware cost, and greater generality. The use of SPR is especially appropriate in monitoring the binding of combinatorial products because these products will not all have labels or properties such as fluorescence that one could monitor. An extension of surface plasmon resonance is the ability to combine this technique with others such as mass spectrometry. An example would be if a signal is detected on the SPR sensors indicating binding, a second technique could be used to identify the bound material.
Basic Grating Coupled Surface Plasmon Resonance Physics and Behavior
Surface Plasmon Resonance
The propagation of electromagnetic wave is expressed in terms of the waves equation as
E
(
x,t
)=
E
0
exp
i
(
K
x
x−&ohgr;t
) (1)
where K
x
and D represent the wave vector in the x-direction and the angular frequency of the wave, respectively. The terms, x and t are distance and time, respectively. The plasmon wave vector is given by
K
x
=2
&pgr;v[&egr;
0
+&egr;
1
]
½
=(&ohgr;/
c
)[&egr;
0
&egr;
1
/(&egr;
0
+&egr;
1
]
½
=(2&pgr;/&lgr;)[&egr;
0
&egr;
1
/(&egr;
0
+&egr;
1
]
½
. (2)
where &egr;
0
and &egr;
1
are dielectric constants of dielectric compound and metal and &lgr; is the wavelength of the exterior light. Twice the imaginary part of K
x
, 2K
xi
, determines the distance the plasmon electric field decays to 1/e along the metal surface.
Gratings provide the standing wave vector parallel to the boundary depending on the groove space and order of the grating. Thus, resonance absorption occurs when the exterior light wave vector component in the boundary plus the grating vector equal to the plasmon vector as given by
(&ohgr;/
c
)sin &thgr;+2
&pgr;m/a
=(&ohgr;/
c
)[&egr;
0
&egr;
1
/(&egr;
0
+&egr;
1
)]
½
(3)
where a and m
Bahatt Dar
Cahill Jerry E.
Nishikida Koichi
Picozza Enrico G.
Saviano Paul G.
Abutayeh M.
Applera Corporation
Epps Georgia
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