Optics: measuring and testing – Of light reflection
Reexamination Certificate
2000-01-28
2004-05-18
Font, Frank G. (Department: 2877)
Optics: measuring and testing
Of light reflection
Reexamination Certificate
active
06738141
ABSTRACT:
FIELD OF INVENTION
The present invention relates to surface plasmon resonance (SPM) sensors. More particularly, the present invention relates to the field of water quality monitoring, where there is a need for sensors being able to measure a large amount of different compounds having the potential of polluting our water resources. Other possible applications are food quality monitoring, process control, biological components including human immunodeficiency virus (HIV) core protein detection and in gene expression monitoring.
BACKGROUND OF THE INVENTION
Surface plasmons (SPs) are normal modes of charge density that exists at the interface between a dielectric and a metal/semiconductor. It was discovered 30 years ago that the coupling between SPs and the electromagnetic field of light is sensitive to the changes in the optical properties of the dielectric medium close to a metal surface. SPR sensors have attracted attention primarily for medical and environmental applications.
Monitoring of different analytes may be determined by an array of different molecular recognition elements (MREs), each element having a specific response to a particular analyte. The MREs can be biological, biochemical or chemical recognition elements or a combination of these elements.
MREs can for example be immobilized directly on the surface of a metal film supporting SP waves at resonance with the light (SPR metal film), e.g. through thiols binding to a gold surface.
Alternatively, the MREs can be immobilized for example through covalent binding in a suitable polymer film (e.g. hydrogel) that is a few hundred nanometers thick coating the SPR metal film. Depending on applications, various sensing schemes of MREs have been reported including antibody-antigen reactions, arrays of oligonucleotides or probes originating from cDNA libraries for DNA hybridization analysis, molecular imprinting techniques, ionic interaction with ionophores and chromo-ionophores, and electrochemical interaction where the SPR metal film acts as one of the two electrodes (the cathode or the anode). Although these MREs are very different in nature, they have the inherent property that they all make use of surface or interface sensitive bio-/chemical interactions, and these interactions can quantitatively be monitored using a SPR sensing scheme.
Since SPs propagate in the transverse magnetic mode (TM mode), optical excitation is only possible in cases where the electric field is polarized parallel to the incident plane (TM polarization) and the wave vectors of the light and the SP are matched. The wave vector k
SP
of the SP at the metal/dielectric interface (i.e. the interface between the metal and the sample to be measured) and at a wavelength &lgr; is given approximately by:
k
SP
~
2
π
λ
ϵ
m
ϵ
s
ϵ
m
+
ϵ
s
(
1
)
where &egr;
S
and &egr;
m
are the real parts of the dielectric constants of the sample and the metal, respectively. The incident light cannot couple directly to SPs on smooth surfaces, since for negative values of &egr;
m
as is the case for metals, the wavevector for the light and the SP can never be matched. SPs can be excited either electronically, optically using a grating or optically using coupling of evanescent waves of light to a metal surface. The latter approach is often performed using the Kretschmann configuration, which consists of a thin metal film coating one face of a high index prism (n
p
~1.4-1.7).
Light passing through the prism increases momentum and is totally reflected from the metal surface at an angle &thgr;, which is greater than the critical angle between the prism and the sample. The component of the wave vector of light k
ev,
being parallel to the metal/dielectric interface and incident on the metal surface with a wavelength &lgr;, is given by:
k
ev
~
2
π
λ
ϵ
g
sin
θ
(
2
)
where &egr;
g
is the dielectric constant of the prism. The parameters &egr;
m
and &egr;
g
are usually fixed and &egr;
S
is the dielectric constant of the sensing area to be measured and its value changes according to the analyte detection. At wave vector matching, k
SP
=k
ev
, the light interacts strongly with the SP giving rise to a large decrease in the reflectivity of the light from the metal/dielectric interface. This condition characterizes the SPR and can be measured using various methods including focusing a beam with an angular band of the light covering the SPR angle, scanning the wavelength of the incident light or a combination of both methods.
A commercial SPR system from the company BlAcore is based on a Kretchmann configuration, but where the SPR metal film is disposed on a replaceable glass plate which is physically separated from a glass prism by means of a refractive index matching gel disposed in between the glass prism and the glass plate. This instrument is large and expensive and there has been much effort in the art to provide small and compact SPR sensors.
U.S. Pat. No. 5,629,774 describes a portable SPR sensor with the object of measuring analyte in a fluid. The sensor comprises a monochromatic light source, a surface plasmon resonance-sensitive device for reflecting the light and a detector based on one or more photo-detectors combined with an “opening” such as a pin hole. The “opening” defines a particular angle on the critical side of the SPR resonance minimum. Small changes in the sample produces large changes in the reflected intensity monitored by the light detector. Compared to systems employing a scanning mechanism or using a focusing light beam with an angular band of light covering the SPR angle, a disadvantage of the system described in U.S. Pat. No. 5,629,774 is related to the use of a single detector which requires a more precise alignment of the system.
In EP 0 797 090, all mirrors, the sensing layer, the photo-detector array and optionally the light source are integrated in the same house. A disadvantage of this configuration is the fact that all components have to be replaced when replacing the sensing layer.
Optional configurations have been described in EP 0 797 091, where a transparent base housing and a detachable prism-like optical housing are index matched to avoid undesirable refraction of the light rays. This is performed using index matching gel between the base housing and the optical housing or fabricating concave portions in the base housing and complementary convex portions in the optical housing at the intersections between the two housings. Both options seem to be complicated solutions for practical working SPR sensors.
It is a disadvantage of the above-mentioned systems that these systems apply an index matching gel. The gel is inconvenient to work with and it may cause problems if comes in contact with some of the optical or bio-/chemical elements.
EP 0 805 347 describes a surface plasmon sensor where the metal layer supporting the surface plasmons is positioned on a glass substrate. An incoming optical light beam is directed towards the metal layer using a first transmission grating. The incoming optical light beam is also focussed by the first transmission grating. The directed optical light beam is reflected off the metal layer and propagates towards a second transmission grating. The second transmission grating directs the transmitted beam towards a detector.
It is a disadvantage of the sensor described in EP 0 805 347 that the incoming light beam is incident under angle that differs from normal incidence.
Generally in the prior art, the SPR sensing layers, the light sources, the mirrors and the detectors have been arranged in three-dimensional configurations where at least one component is aligned at an angle close to the SPR angle (~50°-80°) compared to the other components. This implies that integration of sensors with large arrays of sensing areas cannot be readily made. Integration shall preferably be carried out laterally, which requires a planar configuration of layers or planar configurations aligned parallel to
Font Frank G.
Harness Dickey
Merlino Amanda
Vir A/S
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