KR20010110428A - A surface plasmon resonance sensor - Google Patents

Abstract

The present invention relates to a surface plasmon resonance sensor comprising a first unit and a second unit, wherein the first unit and the second unit are separable, and the first unit comprises a first housing, an electrical The film being positioned on a second outer surface portion of the first housing to receive an optical light beam from the second unit, the film being held by a first outer surface portion of the first housing; Optical input means located on the third outer surface portion of the first housing to transmit the optical light beam to the second unit, optical receiving means for receiving the received optical light beam from the first unit toward the electrically conductive film A first set of optical elements adapted to direct an optical light beam from an electrically conductive film to optical output means And a second set of optical elements adapted to transmit an optical light beam from an electrically conductive film to a second unit, said second unit comprising a second housing, means for emitting an optical light beam, An optical output means positioned on a first outer surface portion of the second housing for delivering the prepared optical light beam to the first unit, a second set of optical elements arranged on the second outer surface portion of the second housing, An optical input means located on the outer surface portion for receiving the optical light beam from the first unit, a detection means adapted to detect the optical light beam received from the first unit, a detector for detecting the received optical light beam from the first unit to the detection means And a second set of optical elements adapted to be located at positions of the optical input means and the optical output means The propagation direction of the optical light beam is essentially perpendicular to the outer surface portion of the first housing and the second housing so that the optical light beam excludes refraction of the optical light beam when entering the first unit and the second unit A surface plasmon resonance sensor is described.

Description

A SURFACE PLASMON RESONANCE SENSOR

Surface plasmon (SPs) refers to the normal mode of charge density that exists between the dielectric and the interface between the metal and the semiconductor. It has been discovered 30 years ago that the coupling between the SPs and the electromagnetic field of the light is sensitive to changes in the optical properties of the dielectric medium adjacent to the metal surface. Surface plasmon resonance (SPR) sensors have attracted a great deal of attention for applications in the medical and environmental fields.

Examining different analytes is determined by the arrangement of different Molecular Recognition Elements (MREs), each of which has a specific response to a particular analyte. MREs can be biological, biochemical or chemical cognitive elements or compounds of these elements.

For example, MREs can be directly fixed through thioles binding to a metal film (SPR metal film) surface, such as a gold surface, that supports SP wavelengths when resonated with light.

Alternatively, for example, MREs can be immobilized through covalent bonds in a membrane of a few hundred nanometers thick covering a suitable polymeric membrane (e.g., adrogel), i.e., an SPR metallic film. According to the application, various methods of detecting MREs have been reported, including probes starting from cDNA libraries for antigen-antibody reactions, oligonucleotide sequencing or DNA mating assays, molecular imprinting techniques, Ionic interaction between an ionophore and a chromo-ionophore, and an electrochemical reaction where the SPR metal film acts as one of two electrodes (cathode or anode) Interactions. Although such molecular recognition elements, or MREs, are inherently very different in nature, they all have unique properties that use boundaries that are sensitive to surface or biological / chemical interactions and that these boundaries are monitored quantitatively using SPR sensing methods .

Since SPs propagate in transverse magnetic mode (TM mode), optical excitation is possible only when the electric field is polarized parallel to the inclined plane (TM polarized light) and the wavelength vectors of light and SP coincide with each other. The metal / dielectric interface (i. E., The interface between the metal and the sample to be measured) The wavelength vector of SP Is approximated as follows.

(One)

here Wow Are the real part of the dielectric constant of the sample and metal, respectively. The tilt angle on a smooth surface can not be coupled directly to SPs, as in the case of metal When this value is negative, the wavelengths of light and SP can not coincide with each other. SPs can be electrically excited by optically using gratings or by optically using wavelengths that are gradually evanescent to the metal surface. The latter approach is often performed using a Kretschmann configuration, which is a high index prism To 1.4 - 1.7) is made of a thin metal film coated with a coating.

Light traveling through the prism increases the amount of motion, , The angle is greater than the critical angle between the prism and the sample. Parallel to the metal / dielectric interface and wavelength And the light inclined on the metal surface The components of the wavelength vectors of the wavelength bands are given as follows.

~ (2)

here Is the dielectric constant of the prism. parameter Wow Is usually fixed Is the dielectric constant of the sensing area to be measured and its value depends on analyte detection. , The light interacts strongly with the SP, where the reflectivity of the light from the metal / dielectric boundary is significantly reduced. These conditions can be measured using a variety of methods, including characterizing the SPR, focusing the beam with an angular range of light to cover the SPR angle, scanning the wavelength of the oblique light, or using a combination of the two methods.

A commercial SPR system produced by a company called BIAcore is based on the method of setting the clamp only, but the SPR metal film is placed on a replaceable glass plate, which lies between the glass prism and the glass plate, And is physically separated from the glass prism by the refractive index. These instruments have been devoted to the development of technology to provide a compact, high-priced and compact SPR sensor.

U.S. Patent No. 5,629,774 discloses an SPR sensor that can be conveniently used for the purpose of measuring analytes in a fluid. The sensor consists of a monochromatic light source, a surface plasmon resonance-sensitive device for reflecting light, and a detector based on one or more light-detectors combined with "openings" such as pin holes. The " aperture " defines a special angle on the critical plane of the SPR minimum resonance. A small change in the sample creates a large change in the intensity of the reflection, which is checked by the photodetector. Disadvantages of the system are disclosed in U.S. Patent No. 5,629,774, as compared to a system using a scanning mechanism or a method of focusing a light beam with an angular width of light to cover an SPR angle, To the use of a single detector requiring alignment.

In EP 0 797 090 all reflectors, sensing layers, light-detector arrays, and light sources are optimally integrated in the same house. The disadvantage of this shape is that all components must be replaced when replacing the sensing layer.

Optional features are disclosed in European patent EP 0 797 091 wherein the optical housing such as a transparent basic housing and a removable prism is indexed to preclude undesirable refraction of the projected light. This can be accomplished using a method of indexing the gel between the base housing and the optical housing, or a method of making a concave portion in the base housing and a method of making an auxiliary convex portion in the optical housing at the interface between the two housings. Two alternative methods seem to be somewhat complicated as a solution for practical operation of the SPR sensor.

A disadvantage of the system mentioned above is that such systems apply index matching gels. Handling gels is inconvenient and may cause problems when in contact with a series of optical elements or biological / chemical elements.

EP 0 805 347 discloses a surface plasmon sensor when a metal layer supporting a surface plasmon is located on a glass substrate. The incoming optical light beam is directed to a metal layer using a first delivery grating. The incoming optical light beam is also focused by the first transmission grating. The direct optical light beam is reflected off the metal layer and propagates toward the second transmission grating. The second delivery grating directs the transmitted beam to the detector.

A drawback of the sensor disclosed in EP 0 805 347 is that the incoming light beam is inclined at an angle different from the normal slope.

In general, in the prior art, the SPR sensing layer, the light source, the reflector, and the detectors are arranged in a three-dimensional shape so that at least one component has an angle close to the SPR angle (~ 50 to 80 degrees) Lt; / RTI > This means that it is desirable for the integration operation to be performed in the transverse direction, in which the planar or planar shapes of the layers need to be aligned parallel to one another.

Therefore, in a simple portable SPR sensor according to the prior art, it is not necessary to use an index matching gel, and a sensor chip capable of distributing only non-systematic alignment between the sensor chip and the optical transducer needs to be configured to have an array of a plurality of detection regions .

An object of the present invention is to provide an SPR sensor constituted by one sensor chip fabricated with a planar sensor chip unit (SCU) having an arrangement arrayed in the transverse direction.

Another object of the present invention is to provide an SPR sensor constituted by a transversely integrated array of planar optical transducer units.

Yet another object of the present invention is to provide an SPR sensor composed of two detachable unit-sensor units and a transducer unit.

It is a further object of the present invention to provide an SPR sensor with a non-critical alignment between the sensor unit and the transducer unit.

It is another object of the present invention to provide an SPR sensor in which the use of an index matching gel is excluded.

The present invention relates to a surface plasmon resonance (SPM) sensor. More particularly, the present invention relates to the field of observing water quality when a sensor capable of measuring large amounts of different compounds, including potential elements that can contaminate our water resources, is needed. Other possible applications include biological components including food quality testing, process control, detection of core proteins in human immunodeficiency virus (HIV), and gene expression testing.

FIG. 1 is a schematic view of a conventional surface plasmon resonance sensor based on reflection graphs of corresponding light reflected from a surface plasmon sensing area represented by a Kratzmann shape and an inclination angle. There is a plot of the case where there is no analytical response (curve represented by solid line) and the case where there is analytical response (curve represented by dotted line).

Fig. 2 schematically shows a cross section of sensor chip units (SCUs) for five different shapes (a-e) according to the invention.

3 schematically illustrates an optical transducer unit separated by a gap according to a sensor chip unit and a corresponding preferred embodiment of the present invention, wherein the embodiment includes a substantially monochromatic light source and an SPR angle And is based on the interlocking of light in angular bands. a), the sensor chip unit is shown for a case where the SPR angle is -60 degrees, and b) the sensor chip unit is shown for the case where the SPR angle is -75 degrees. The projected lights starting from the light source are indicated by solid lines.

Fig. 4 shows two different embodiments according to the invention, each having a sensor chip unit and a corresponding optical transducer unit separated by a gap. The shape in Fig. 4 (a) is based on a multicolor light source with a fixed interlocking angle, and a grating is provided in the optical transducer, so that the width of the spectrum of light can be measured. The projected light originating from the light source is drawn as a solid line. The shape in Fig. 4 (b) is based on interlocking of light in each range including monochromatic light source and SPR angle. The projected light from the first light source is drawn in solid lines and the projected light from the second light source is drawn in dotted lines.

Figure 5 shows a top view of an embodiment of the invention from Figure 4 (a) consisting of the sensor chip unit of a) and the optical transducer unit of b). c) and d) each show two sensor chip units and two optical transducer unit arrangements (e) and (f) each showing an arrangement of four sensor chip units and four optical transducer units have.

FIG. 6 is a simplified view of a cross-sectional view of a corresponding optical transducer unit separated by a gap from a sensor chip unit in a fourth embodiment of the present invention based on interlocking of light in a range covering a single color light source and an SPR angle. In this configuration, the sensing area is located on the rear side of the sensor chip unit.

Fig. 7 shows a plan view for an embodiment of the present invention, which has one sensor chip unit of a) and a corresponding optical transducer unit of b) as shown in Fig. c) and d) each show two sensor chip units and two optical transducer unit arrangements, and e) and f) each show four sensor chips and four optical transducer unit arrangements.

8 is a cross-sectional view of an optical transducer unit and one sensor chip unit separated by a gap in the lower embodiment of the present invention based on the interlocking of angles in the respective angles covering the monochromatic light and the SPR angle. After being reflected from the SPR sensing area, the projection light is reflected multiple times between the rear side and two planar mirrors on the top-most side of the sensor chip unit.

9 (a) shows examples of a reflective diffractive optical element (RDOE) used in the invention of the present invention, in which a hole D, a grating distance a _p and a grating angle . Fig. 9 (b) shows a parallel collimated projection light that is reflected by the projection light and is converged on one side of the RDOE of (a). Fig. Fig. 9 (c) shows another example of the RDOE, wherein the parallel collimated projected light is reflected by the projection light collimated to one side of the RDOE.

Fig. 10 (a) shows the hole D, the grating distance a _p , And the second grid angle for the p'th grid element Lt; RTI ID = 0.0 > RDOE < / RTI > 10 (b) shows a parallel collimated projection light that is reflected by the projection light and is converged to focus at one side of the RDOE of (a). Fig. 10 (c) shows another embodiment of the RDOE, wherein the collimated collimated light is reflected by the collimated collimated light on one side of the RDOE.

The above-mentioned objects are achieved by first providing a surface plasmon resonance sensor composed of a first unit and a second unit, wherein the first unit and the second unit are separable,

- a first housing,

A membrane made of an electrically conducting material applied to a supporting surface plasmon, said membrane being a membrane maintained by a portion of a first outer surface of said first housing,

Optical input means located on the second outer surface portion of the first housing to receive the optical light beam from the second unit,

Optical output means located on the third outer surface portion of the first housing for transmitting the optical light beam to the first unit,

A first set of optical elements adapted to direct the received optical beam of light to a film that electrically conducts from the first unit,

A second set of optical elements adapted to direct the optical output means from a film that conducts the optical light beam in order to transfer the optical light beam from the electrically conducting film to the second unit,

The second unit comprising:

- a second housing,

Means for emitting an optical light beam,

A first set of optical elements adapted to prepare the emitted optical light beam,

Optical output means located on the second outer surface portion of the second housing for transmitting the optical light beam prepared from the first unit,

- detection means adapted to detect an optical strong beam received from the first unit,

A second set of optical elements adapted to direct the received optical light beam from the first unit to the detection means,

Wherein the direction of propagation of the optical light beams at the locations of the optical input and optical output means is essentially perpendicular to the outer surface portion of the first and second housings, And excites the refraction of the light beam.

In the aspects of the present invention mentioned above and in the following description, the term essentially perpendicular means that the inclination angle is in the range of -10 degrees to 10 degrees, preferably -5 degrees to 5 degrees, and -2 More preferably in the range of -0.5 degrees to 0.5 degrees, and more preferably in the range of -0.5 degrees to 0.5 degrees.

This emitting means is composed of a laser light source such as a semiconductor laser diode. The light emitting means can essentially emit light at a single wavelength. Optionally, the light emitting means may emit light at a plurality of wavelengths, for example, using one emission diode.

The first set of optical elements of the first unit may be configured as means for aiming the emitted optical light beam in the same direction. The aiming means may be a lens device.

By parallel aiming is meant the diffusion of each beam of emitted optical light beam is 10 degrees or less, preferably 5 degrees or less, more preferably 2 degrees or more, more preferably, And preferably not more than 0.5 degrees.

The first set of optical elements of the second unit may further comprise means for polarizing the emitted optical light beam. Such a polarizing means can be of a kind such as a polarizing film, a prism device or a voltage controlled variable retarder.

The input and output means of the first unit and the second unit may be configured as anti-reflecting coating.

The detection means may comprise an array of light sensitive elements such as a multi-optical detection arrangement, a charge coupled device or an auxiliary metal oxide semiconductor image sensor. The sensor may further comprise a light protection component. The first set of optical elements of the first unit may be comprised of a diffractive element such as a diffractive grating or a holographic grating. In a similar manner, the second set of optical elements of the first unit may comprise diffractive elements that may be comprised of reflective elements. Also, the second set of optical elements may be comprised of reflective components such as reflective mirrors (mirrors).

The electrically conductive film may be composed of a metal film such as a gold film, a silver film, an aluminum film, or a titanium film. The electrically conductive film may comprise a plurality of electrically conductive films, the plurality of films being arranged in a pattern extending in the transverse direction.

The dielectric material of the single strand can be positioned between the electrically conductive film and the first outer surface portion of the first housing to support surface plasmon resonance in a long range. If the surface plasmon resonance sensor is comprised of a plurality of electrically conductive layers, the sensor may include a layer of dielectric material disposed between each of the plurality of electrically conductive films and the first outer surface portion of the first housing ≪ / RTI >

The surface plasmon resonance sensor may further comprise a moving means adapted to move the first unit and the second unit about each other to move the focus of the optical light beam about an electrically conductive film. In addition, the surface plasmon resonance sensor may be configured to move the first unit and the second unit around each other, and may be configured to move the inclination angle of the optical light beam toward the electrically conductive film.

Preferably, the surface plasmon resonance sensor comprises two or more surface plasmon resonance sensors, and the sensor is arranged in a pattern extending in the transverse direction.

In a second aspect, the present invention relates to a method for determining a biological / chemical composition of a sample using a surface plasmon resonance sensor, wherein the surface plasmon resonance sensor is comprised of a first unit and a second unit, Two units are capable of being separated, the first unit comprising:

- a first housing,

A membrane applied to the supporting surface plasmon and made of an electrically conductive material, the membrane being held by the first outer surface portion of the first housing.

Optical input means located on the second outer surface portion of the first housing to receive the optical light beam from the second unit,

Optical output means located on the third outer surface portion of the first housing for transmitting the optical light beam to the second unit.

A first set of optical elements in which the received optical light beam is directed from the first unit to an electrically conductive film,

A second set of optical elements adapted to direct the optical light beam from the electrically conductive film to the optical output means and to transfer the optical light beam from the electrically conductive film to the second unit,

The second unit comprising:

- a second housing,

Means for emitting an optical light beam,

A first set of optical elements adapted to prepare an emitted optical light beam,

Optical output means located on the first outer surface portion of the second housing for delivering the prepared optical light beam to the first unit,

Optical input means located on the second outer surface portion of the second housing to receive the optical light beam from the first unit,

Detection means adapted to detect an optical light beam received from the first unit, and

A second set of optical elements adapted to direct the received optical light beam from the first unit to the detection means,

Wherein the propagation direction of the optical light beam at the optical input and optical output positions is essentially perpendicular to the outer surface portions of the first housing and the second housing such that when the optical light beam enters the first unit and the second unit, So that the refraction of the beam is excluded.

In a third aspect, the present invention relates to a surface plasmon resonance sensor comprising a first unit,

- a first housing,

A layer of an electrically conductive material applied to the supporting surface plasmons, said layer being held by a first outer surface portion of the first housing,

Optical input means located on a second outer surface portion of the first housing, the optical input means being adapted to receive an optical light beam,

An optical output means located on a third outer surface portion of the first housing, the optical output means being adapted to transmit an optical light beam;

A first diffractive optical element adapted to direct the received optical light beam to an electrically conductive layer,

A second diffractive optical element adapted to direct the reflected optical light beam from the electrically conductive layer towards the optical output means,

Characterized in that the propagation direction of the optical light beam at the location of the optical input and optical output means is essentially perpendicular to the outer surface portion of the first housing, excluding the optical input and the refraction of the optical light beam at the location of the optical output means Surface plasmon resonance sensor.

The surface plasmon resonance sensor according to the third aspect may further comprise a second unit,

- a second housing,

Means for emitting an optical light beam,

A set of optical elements adapted to prepare the emitted optical light beam,

Optical output means located on the first outer surface portion of the second housing, the optical output means being adapted to transmit the prepared optical light beam to the first unit,

An optical input means located on a second outer surface portion of the second housing, the optical input means being adapted to receive an optical light beam from the first unit,

- detection means adapted to detect an output light beam received from the first unit,

Wherein the propagation direction of the optical light beam at the location of the optical input and optical output means is essentially perpendicular to the outer surface portion of the second housing to exclude the diffraction of the optical light beam at the location of the optical input and optical output means Surface plasmon resonance sensor.

The second unit may further comprise an optical element which is adapted to direct the received optical light beam from the first unit to the detection means.

The light emitting means may be constituted by a light source described in the first aspect of the present invention. The optical element set of the second unit may be constituted by the light aiming means and the polarization means described in accordance with the first aspect of the present invention.

The input and output means of the first unit and the second unit may be surface-treated with semi-reflective coating.

As in the first aspect of the present invention, the detection means may comprise an arrangement of light sensitive elements such as a multi-optical detection arrangement, a charge coupled device or an auxiliary metal oxide semiconductor image sensor. The first and second diffractive optical elements of the first unit may be composed of an optical grating such as a reflective holographic grating.

In a fourth aspect, the present invention relates to a surface plasmon resonance sensor constituted as follows. That is, in the surface plasmon resonance sensor,

- transparent components,

A layer of an electrically conductive material adapted to support surface plasmons, said layer being held by an outer surface portion of the component; a layer of electrically conductive material,

A first optical grating held by a first outer surface portion of the component and adapted to face the received optical light beam towards an electrically conductive layer, the propagation of the optical light beam received at the location of the first optical grating Direction is essentially perpendicular to the first outer surface portion of the component, wherein the received optical beam is collimated in a first direction,

- is adapted to receive the optical light beam from the electrically conductive layer and to re-emit the optical light beam received from the electrically conductive layer, held by a second outer surface portion of the component, Wherein the propagation direction of the re-emitted optical beam at the location of the optical grating is essentially a second optical grating in which the re-emitted optical light beam is collimated in a direction perpendicular to the second outer surface portion of the component Is a surface plasmon resonance sensor.

A surface plasmon resonance sensor according to a fourth aspect of the present invention includes:

- means for emitting an optical light beam.

In addition, the surface plasmon resonance sensor according to the fourth aspect of the present invention may be constituted by an optical element directed to the means for detecting the re-emitted optical light beam.

The light emitting means may be constituted by the light sources described in the first and third aspects of the present invention. The optical element set of the second unit may be composed of a parallel aiming means and a polarization means.

The means for detection may comprise an arrangement of light sensitive elements such as a multi-optical detection arrangement, a charge coupled device or an auxiliary metal-oxide semiconductor image sensor.

FIG. 1 shows the shape of a claw of a conventional SPR sensor. The SPR sensor includes a high index prism 2, a thin metal film 1 coated on one side of the prism, Biological / chemical sensing thin-film regions. The use of the lens 4 and parallel collimation of the monochromatic light is performed through the prism 2 focusing on the metal film. The light beam has a specific light width D from Is banded on the metal film. The other lens 5 images the light beam reflected from the metal film onto the detector array 6. The range of SPR angle And the angle is determined by the detector arrangement 6 such that the reflectivity of the light is minimized. When a change occurs in the ambient condition 7, the layer thickness or refractive index of the biological / chemical sensing area 3 changes. As schematically shown in Figure 1, This causes a change in the SPR response, where the solid line SPR curve moves to the position of the SPR curve indicated by the dashed line.

The present invention relates to a measurement principle that is based on imaging each band range or wavelength range onto a single detector array. All components of the present invention may be commercially available or may be manufactured using existing manufacturing techniques. The SPR sensor is a combination of the following:

1) a replaceable sensor chip composed of planar sensor chip units (SCUs) arranged in an array in the lateral direction;

2) an optical transducer composed of a planar optical transducer unit (OTUs) arranged in an array in the transverse direction.

The shapes of the five different sensor chip units (SCUs) according to the present invention are shown in Fig. 2 (a-e). A collimated collimated beam of light, which enters the SCU perpendicularly to the rear surface of the SCU, is transmitted through the first set of optical elements 18a to the top surface of the SCU and to the SPR film < RTI ID = 0.0 > (20). The light beam reflected from the SPR metal film through the second set of optical elements 22a is collimated and exits the SCU perpendicular to the rear surface of the SCU.

In Fig. 2 (a), a first set of optical elements, a second set of SPR metal films and optical elements, are arranged on the uppermost side of the SCU, and a reflector is arranged on the back side of the SCU. In Figures 2 (b) - (d), a first set of optical elements and a second set of optical elements are disposed on top of the SCU, and the SPR metal film is disposed on the back side of the SCU. In Figure 2 (e), a first set of optical elements and a second set of optical elements are disposed on the back side of the SCU, and a metal film is disposed on the uppermost side of the SCU. The present invention is based on the assumption that the light beam propagated in the SCU is focused on the SPR metal film as in Figures 2 (a), (b) and (e) The light beam propagated in the SCU between the set and the second set of optical elements is focused or propagated in the SCU covers a shape in which the light beam is collimated as in FIG. 2 (c). In the case of the features shown in Figures 2 (a-d), the first and second sets of optical elements are either mirrors (cylindrical parabolic mirrors) or reflective diffractive optical elements (RDOE). In the case of the configuration shown in Fig. 2 (e), the first and second sets of optical elements are lenses, microlens arrays or transmissive diffractive optical elements.

Fig. 3 shows a first embodiment and a preferred embodiment of the present invention, in which the SCU and optical transmission unit OTU 11 shown in Fig. 2 (a) are separated by a support frame 12, The frame 12 leaves a gap 13 between the two units.

The light beam emerging from the monochromatic light source 14 provided in the base surface 31 is collimated by the lens or lens system 15 and is polarized by the polarizer 16. The light beam enters the SCU 10 perpendicularly to the rear side of the SCU through the transparent separating surface 17. Shielding light from the light source 14 and light reflected from the surface of the detector 23 are blocked by the light protection dog 8. Inside the SCU, a light beam is reflected from the reflective diffractive optical element (RDOE) 18a and converts the light beam into a light beam that is cylindrical focused. Through a flat reflector 19 disposed on the back side of the SCU, one line above the SPR metal film 20 where the light beam is successively reflected and placed under one or more sensing areas 21 on the top Focused. The focused light beam consists of the respective bands covering the SPR angle. After being reflected from the SPR metal film 20, the light beam is reflected from the plane mirror 19. Is converted back into a collimated collimated beam through the second RDOE 22a and exits the SCU perpendicularly to the rear side of the SCU and reenters the OTU perpendicular to the transparent separation plane 17. The planar surface 24 provided in the basal plane coupled with the planar surface 25 provided in the center of the transparent separation plane imaged the collimated beam of light onto the detector array 23. Alternatively, mirrors 24 and 25 may be omitted as an alternative to this, or they may be replaced by other optical means such as a lens system.

Typically, the gap between the SCU 10 and the OTU 11 is filled into the atmosphere, and since the reflection index of the substrate material of the SCU is ~ 1.6, the internal critical angle for total reflection is to be. this is So that the planar diameter on the rear side can be simply the natural reflection of the light beam from the air / substrate contact. In applications where the sensor is immersed in water and water forms a film in the gap, The And a metal mirror may be needed on the back side of the SCU.

The optical interconnect between the sensor chip and the optical transducer is based on a parallel collimated light beam propagating perpendicular to the plane crossing between the optical transducer, the gap and the sensor chip. Thus, the direction of the light beam does not change as it passes through the planar intersection. As a result, the vertical alignment of SCUs and OTUs is not a critical factor, and the operation of the sensor is dependent on the magnitude of the refractive index of the gap, which eliminates the need for an index matching gel It is not sensitive.

In addition, it combines the focus and collimating optics in the sensor chip with a large light beam diameter that encompasses sufficiently large bands to ensure an uncritical alignment in the horizontal direction. Partial reflections from the intersection between air / plastic or air / glass are usually ~ 4%, which is reduced to ~ 0.5% by associating the semi-reflective coating on the planar intersection. An available semi-reflective coating material is Wow .

3, the SPR angle of a) is ~ 60 degrees and the SPR angle of b is ~ 75 degrees, and sensor chips having different ranges of SPR angles can be used for the same optical transducer . Means are provided for integrating the plurality of sensing areas 21 on the same sensor chip by lateral integration of the planar sensor chip unit and the planar optical transducer unit. Each sensing region 21 typically consists of a polymer membrane with fixed molecular recognition elements (MREs) that are specifically responsive to a particular analyte. Recipe for the arrangement of polymer membrane tissue includes ink jet printing technology and micro-machined microdispensers.

In the configuration shown in FIG. 3, the mirrors 24 and 25 are flat and the width of the light beam impinging on the detector array will remain unchanged. In this case, since the inclination angle is larger than 0 degrees and exists between 20 degrees and 45 degrees, the area on the detector array illuminated by the light beam will become larger than the cut area of the light beam. The resolution of the SPR measurement is increased, but the response of the detector array will soon fall, compared to the shape in which the light beam does not have mirrors (24 and 25) collide with a 0 degree tilt angle on the detector array. Since the light intensity from the light source is sufficiently large, the response drop of the detector array is not considered a major problem in this configuration.

The resolution of the detector array is such that the resolution of the detector array is such that one or both of the planar mirrors 24 and 25 emit a light beam passing through at least one convex mirror, concave convex lens or separate plane 17, Can be further improved by replacing the system with a diffractive optical element that increases the area.

The light source may be a laser diode comprising a surface emitting laser diode, a light emitting diode (LED) or other monochromatic light source. For example, Hitachi HI-L520RNC, Hitachi, Japan, a light emitting diode emitting at 700 nm, Toshiba TOLD9221M InGaAIP of Japan Toshiba Corporation, which is a multi-quantum storage laser diode emitting at 670 nm, a multi-quantum storage laser diode Mitsubishi ML40123N AlGaAs from Mitsubishi, Japan, or Honeywell GaAs Vertical Cavity Surface Emitting Laser diode SV2637-001 from Honeywell, USA, emitting at 850 nm. The lens 15 collimates the light beam emitted from the light source 14 with an aspheric lens or an aspherical lens system. For light beams, the lens is made of a transparent material, such as glass or plastic. The polarizer may be a passable optical component having a fixed direction of polarization, or a voltage controlled variable delay consisting, for example, of a liquid crystal or LiNbO3 crystal. The light emitted from the laser diode usually has well-defined polarization, but the light from the LED is usually not well-defined and the polarizer can be used to optimize the visibility in the SPR response. The selection of the detector 23 is determined by the size of the sensor and the required resolution. This may be achieved by using multiple photodiode arrays (e.g., Hamatsu S3921-128Q, F with an array of 129 pixels), CCD devices (e.g. SONY ICX059CL with 795 x 596 pixel array) or auxiliary metal oxide semiconductor image sensors (e.g. Vision VV5405 Monochrome CMOS image sensor with integrated 356 x 292 pixels).

FIG. 4 illustrates two alternative embodiments according to the present invention, each having a corresponding OTU separated by a gap from the SCU. The second embodiment of the present invention as shown in Fig. 4 (a) comprises an SCU as shown in Fig. 2 (c), but has an additional reflector and OTU disposed on the rear side of the SCU, (14) is a white light source (e.g., a white LED lamp manufactured by Nichia Chemical Industries, Ltd.). The planar mirror 25 according to the first embodiment of the invention has been replaced by a diffraction grating or a holographic grating. The SPR angle is kept constant and the detector array 23 measures the length of the optical wavelength corresponding to the wavelength corresponding to light and SP. The grating 25 diffracts the light to image the light on different pixels in the detector array according to the wavelength length of the light. The RDOEs 18a and 22a are now designed to exhibit a minimum wavelength dependent deflection angle, which reflects a collimated collimated beam of light into a collimated collimated beam of light inside the sensor chip unit.

4 (b) shows a third embodiment of the present invention. The third embodiment of the invention consists of the same components as the first embodiment of the present invention (see Fig. 3), the planar mirrors 24 and 25 are omitted, and the third embodiment has the second monochromatic light source 26) is additionally constituted, and the light source 26 radiatively transfers the second light beam. The second light beam is collimated by a second lens or second lens system 27 and is polarized by a second polarizer 28 and passes through a transparent separation plane 17 to enter the SCU 10 perpendicular to the back side of the SCU . Alternatively, the lens system is designed in such a way that the first light beam and the second light beam are generated from the same monochromatic light source and produce a collimated collimated light beam consisting of the first light beam and the second light beam.

Into the interior of the SCU, the second light beam is reflected from a third RDOE 18b that converts the second light beam into a second light beam that focuses cylindrically. Through the planer 19, the second light beam is reflected and focused onto a line on the SPR metal film 20 which is below one or more sensing zones. The second focused light beam is composed of each band covering the SPR angle.

After reflection from the SPR metal film 20 a second light beam is reflected from the planer 19 through the fourth RDOE 22b and converted into a parallel collimated second light beam to form a SCU 10). The second light beam re-enters the OTU 11 perpendicular to the transparent separation plane 18 and is imaged onto the detector array 23.

Fig. 5 shows the structure of the SPR sensor from SCUs and OTUs as shown in Fig. 4 (b). A simple top view for one SCU is shown in Figure 5 (a) with four sensing elements 21a, 21b, 30a and 30b, a metal film 20 and RDOEs 18a, 18b, 22a and 22b have.

Figure 5 (b) shows a top view of a corresponding OTU comprising a transparent separation plane 17, detector arrangement 23, and the component 33 consists of a light source, a lens system, and a polarizer. FIGS. 5 (c) and 5 (d) show sensor configurations composed of two SCUs and corresponding OTUs, and FIGS. 5 (e) and 5 Fig.

The principle of configuring the sensor from SCUs and OTUs can be extended to N units, where N is an integer larger number. The SCUs and OTUs can be aligned by arranging in an array aligned in a direction parallel to the RDOEs (top-down direction in FIG. 5) or by extending the spatial dimension of each component in this direction. The sensor can be selectively expanded by coupling the SCUs and OTUs in a direction perpendicular to the RDOEs (left-right direction of FIG. 5). When operating the sensor, the sensor chip must be installed on top of the optional transducer. Samples making up the analyte are usually dissolved in water and settled on top of the sensing area. This is done by using a distributor or by coupling the sensing area into the flow-injection cell.

A fourth embodiment of the present invention is shown in Figure 6 where RDOEs 18 and 22 are disposed on the uppermost side of the SCU 10 and the SPR sensing layer 21 is disposed on the rear side of the SCU 10 Respectively. The SCU is shown in Fig. 2 (b) and the OTU 11 is shown in Fig. 6, except that the OTU 11 of Fig. 4, except that in both configurations the spacing dimensions of the components and the distance between the components are different, .

6, the light beam from the monochromatic light source 14 provided in the basal plane 31 is collimated by the lens or lens system 15 and is then directed by the polarizer 16 Enters the SCU 10 perpendicularly to the rear side of the SCU after passing through the polarized, transparent separation plane 17. Again, the light protection dog 8 protects the detection array from scattered light projected from the light source 14, thereby eliminating interference between the light emitted from the light source 14 and the light reflected from the surface of the detector array 23. Inside the SCU, a light beam is reflected from the RDOE 18, which converts the light beam into a cylindrically focused light beam, and the focused light beam passes through one or more sensing areas 21 ) On the SPR metal film 20, as shown in Fig. The SPR metal film is disposed on the rear side of the SCU. The focused beam of light contains each band covering the SPR angle. After being reflected from the SPR metal film 20, the light beam is converted into a light beam collimated by the second RDOE 22. The light beam enters the SCU perpendicularly to the rear side of the SCU and reenters the OTU perpendicular to the transparent separation plane 17. A plane mirror 24 provided on the base coupled with a plane mirror 25 located in the center of the transparent separation plane images the collimated beam of light onto the detector array 23. One of the planar mirrors 25 or 24 may be replaced by a convex winter or RDOE with the ability to emit a light beam passing through a separation plane 18 that increases the area on the detector array illuminated by the light beam .

FIG. 7 shows an SPR sensor constructed from SCUs and OTUs shown in FIG. A schematic plan view of one SCU is shown in Fig. 7 (a) with two sensing areas 21a and 21b, metal sensing areas 21a and 21b, a metal film 20 and RDOEs 18 and 22.

7 (b) shows a top view of a corresponding OTU comprising a transparent separation plane 17, mirrors 24 and 25, a detection arrangement 23, a component 33 consisting of a light source, a lens system and a polarizer will be. Figs. 7 (c) and 7 (d) show sensor shapes composed of two SCUs arrays and corresponding OTUs, and Figs. 7 (e) and 7 FIG. The principle of configuring sensors from SCUs and OTUs can be extended to N units, where N is an integer, the larger the larger, the better. The SCUs and OTUs can be arranged in an array aligned in a direction parallel to the RDOEs (up-down direction in Fig. 7) or by extending the spatial dimension of each component in this direction. The sensor may optionally extend SCUs and OTUs in a direction perpendicular to the RDOEs (left-right direction in FIG. 7). When operating the sensor, the sensor chip should be installed on top of the optical transducer. A specific amount of the sample, usually composed of the analyte dissolved in water, is placed on top of the sensing area. This is done using a distributor or using a flow cell installed in the gap between the SCUs array and the OTUs array.

Fig. 8 shows a fifth embodiment of the present invention. As shown in Fig. 4, this consists of the same components in the SCU and OTU, but the first light source and the second light source are now symmetrically disposed about the sensing layer. In addition, the SCU is comprised of a planar surface 40 on the top-most side and the OTU is comprised of planar mirrors 24, 25, 29, which are directed towards the detector array 23 with a first light beam and a second light beam As shown in FIG. The light beam emerging from the monochromatic light source 14 provided in the base surface 31 is collimated by the lens or lens system 15 and polarized by the polarizer 16 and then through the transparent separation plane 17 to the rear side And enters the SCU 10 vertically. Again, the light protection dog 8 protects the detection array from scattered light from the light source 14 and excludes interference between the light from the light source 14 and the light reflected from the detector array 23 surface. Inside the SCU, a light beam is reflected from the RDOE 18a and converts the light beam into a cylindrical focused light beam. Through a plane mirror disposed on the back side of the SCU, the light beam is reflected and focused onto one line on the SPR metal film 20 beneath the one or more sensing areas 21. The focused light beam consists of each band covering the SPR angle. After being reflected from the SPR metal film 20, the light beam is reflected three or more times alternating between the planar view 19 and the planar surface 40 disposed on the top-most side of the SCU. Through the second RDOE 22a, the light beam is again converted into a collimated collimated beam and exits the SCU vertically to the rear side of the SCU and re-enters the OTU perpendicular to the transparent separation plane 17. A mirror 24 mounted on a base coupled with a mirror 25 installed in the center of the transparent separation plane images the collimated beam of light onto the detector array 23.

8, the fifth embodiment of the present invention further comprises a second monochromatic light source 26 installed in the base plane, the base plane 31 having a second collimated collimated collimated by a second lens or lens system 27, Radiate the light beam and are polarized by the polarizer 28 and pass through the transparent separation plane 17 before entering the SCU 10 perpendicular to the back side of the SCU. A second light protection dog 9 protects the detector array from scattered light from the light source 26 and prevents interference between light from the light source 26 and light reflected from the detector array 23 surface.

Inside the SCU, a third light beam is reflected from the third RDOE 22b and transforms the second light beam into a second light beam that is cylindrical in focus. Through the planer 19, the light beam is reflected and focused onto one line on the SPR metal film 20 under one or more sensing regions 21. The second focused light beam is composed of each band covering the SPR angle.

After the reflection from the SPR metal film 20, the second light beam is alternately reflected three or more times, alternating between the plane mirror 19 and the plane mirror 40. Through the fourth RDOE 18b, into a parallel collimated second light beam which exits the SCU perpendicularly to the rear side of the SCU and re-enters the OTU 11 perpendicular to the transparent separation plane 17 do. A second plane mirror 29 provided on the base surface 31 coupled with the plane mirror 25 images the second light beam onto the detector array 23. In an alternative embodiment of the invention, one or both of the planar mirrors 24 and 29 or the planar mirror 25 are replaced by a system consisting of at least one convex mirror, convex lens or diffractive optical element. As a result, the light beam passing through the separation plane 17 will be diverged, thereby increasing the area on the detector array that is illuminated by the light beam. Referring to the fifth embodiment of the present invention as shown in FIG. 8, a sensor chip and an optical transducer are constructed from SCUs and OTUs in a manner similar to the embodiment of the invention shown in FIGS. 4 (b) and 5.

Before exiting the SCU, the light beam in the configuration shown in Fig. 8 is reflected on a larger number of surfaces and travels a longer path distance than the light beam in the configuration shown in Fig. 4 (b). The width of the beam is magnified with a factor of two, since the light beam entering the sensor chip of Fig. 8 is reflected twice before it collides on the SPR film, and then reflected four times after being reflected from the SPR film. For a pixel size of the same detector array, a larger diameter of the beam means that a better resolution can be obtained in the detector array, but the size of the SCU and OTU must also be larger. By widening the length of the zone existing between the sensing zones 21 and 30 and thereby further enhancing the reflection between the planes 19 and 40, the width w of the light beam at the output of the SCU is Can be increased according to the following equation. In this equation, Is the width of the light beam entering the SCU and k is the number of reflections from the mirrors 19 and 40 to the light beam. Immediately before being reflected from the RDOE, it is reflected from the SPR metal film and then the number of reflections from the first reflection is calculated. In the case of reflection from the above-mentioned RDOE, 22b is for the first light beam and (18b) For a light beam. 4 (b), k = 1 and w = w ₀ , and in the case of the shape of FIG. 8, k = 3 and w = 2w ₀ .

Figures 9 (a) and (b) illustrate a design example of the RDOE used in the present invention with two modes of operation. In mode 1 (see (18a) in FIG. 3 (a)), RDOE is the SPR angle ) And reflects the vertically sloped light beam. In mode 2 (see (22a) of FIG. 3 (a)), the RDOE reflects the light beam emitted from the SPR metal film and feeds it to the parallel collimated light beam exiting the SCU perpendicularly to the rear side of the SCU.

The dimensions of the RDOE are shown in Figure 9 (a), where D is the clearance D, Is the lattice distance Is the lattice angle for the pth lattice element. 9 (b) shows a case of mode 1 in which the inclined parallel collimated projection light is converted into projection light for conversion into projection light. The design of the RDOE for Mode 2 is a symmetric image of the design shown in Figure 9 (a) and is in focus and in a plane parallel to the slope. 9 (c) shows another design example for RDOE, which is utilized as an embodiment of the invention as shown in FIG. 4 (a), wherein the parallel collimated projected lights are parallel to one side of the RDOE And is reflected by the aimed projection light.

Figures 10 (a), (b) and (c) show another design example of RDOE where D is a clearance, Lt; / RTI > The grid angle, and Is the second lattice angle for the pth lattice element. The function of such a grating is the same as that shown in Fig. 9, but the shape uses a second grating angle rather than a vertical grating wall.

(E.g., SF2, SF5, SF11 or sapphire), silicon, and combinations thereof with metal evaporation or metal boiling, for example, with respect to the wavelength of light, such as a polymer (e.g., polycarbonate, polystyrene, polyetherimide or polyurethane) RDOEs can be made by using various processing techniques with the same transparent material. The plastic is usually birefringent, but the polarization of the light beam can be adjusted by matching the TM mode of the surface plasmon with a polarizer. Possible processing techniques include one-level gray-tone lithography, diamond turning, photolithography, binary optics, e-beam writing, laser Micro-mechanical etching, and techniques such as analog or digital holographic lighting in photoresists. The processing technique can utilize either a method of directly processing a sensor chip or a method of forming a template of a sensor chip.

The metal film on the top of the RDOEs can be gold, silver, aluminum, titanium or similar materials. The thickness of the metal layer is usually about 200 nm (or more), and it is sufficient to provide sufficient reflectivity, and the thickness of the metal generally exceeding 100 nm will not be able to sustain the SP wave.

The thickness of the SPR metal film is typically ~ 50 nm. Gold or silver will be used for the wavelength range of 400-1000 nm. Materials such as aluminum, copper and titanium can also be used in the infrared. SPR metal film and RDOE metal film have different thicknesses and compositions. Fabrication of such films using a mask (e.g., a metal mask or photolithographic mask) during the evaporation or melting of the metal can be accomplished.

In Figs. 9 (b) and 10 (b), the bandwidth for the optical link for SP The from . For the p-th grid, the corresponding grid angle is Where p = 0 is the first element and p = N is the last element in the lattice. Assuming that the period of the grating is vias larger at the light wavelength, the grating period is calculated from the following formula, which is based on the diffraction condition projected and projected from the interface of each p-grating element being constructed . In other words,

(3)

here Is the wavelength of light, m is the diffraction order, Wow Are the horizontal distance and the vertical distance between the focus of the grating and the position of the p-th grid element, respectively (see Figs. 9 (b) and 10 (b)).

As an example, if the beam width w = 2 mm Lt; Because of And . 9, the depth of the lattice , Whereas in the case of FIG. 10 to be. In such an example, The wavelength of light Lt; / RTI > A lattice in the case of a lattice period which is comparable to the length of the wavelength or smaller than the length of the wavelength can be utilized.

The oblique light beam is collimated to that of FIG. 9 (b) and each diffractive element of RDOE images light on the same focal point. If D is sufficiently wide compared to w, the angle of the sensor chip to the SP wave due to the transverse displacement of the sensor chip relative to the optical transducer Resulting in a change in the temperature. As shown in Figures 2 and 6, for embodiments of the present invention The same facts as mentioned above can be used for coarse adjustment. The lateral displacement (the arrows shown in Figs. 2 and 6) can be performed by micrometer drive by manual or motor. This means that the SCU can be used to encompass a wide range of SPR angles and refraction indices. As an alternative to focusing the light beam on the SPR metal film in each band encompassing the SPR angle, transverse displacement can also be utilized to scan the tilt angle of the light beam on the SPR metal film. In this configuration, the width w of the light beam must be less than 1/20 of D. In the alternative configuration, the RDOEs can be designed as a single array of elements, where each element is shown as a parallel aimed beam (not shown) on the SPR metal film in each band covering the SPR angle, as shown in Figure 9 The beam is focused. As a result, the lateral displacement of the sensor chip relative to the optical transducer results in a corresponding lateral movement of the tilted focus on the SPR metal film. Using this method, the sensing regions can be arranged in a two-dimensional array. The sensor chip may be mounted on a rotating disk and the lateral displacement (see arrows in Figures 3 and 6) may be performed by a motor of the type utilized in the CD player.

Depending on the parameters including the thickness of the metal film, each band covered by the SPR typically has a reflectivity of half the full width , Respectively. In order to obtain a narrow SPR signal, the optimal thickness of the SPR metal film is empirically determined for a particular sensor, typically ranging from 30 to 50 nm. This is determined by the complex dielectric function of the metal, and according to the Drude formula:

[4]

here Wow Are the real and imaginary parts of the dielectric function, respectively Is the wavelength of the plasma Is the impact wavelength.

For example, when gold is used as the SPR metal film, the following can be obtained from the equation (4). In other words, And to be. The following expression Can be used to calculate.

[5]

here Is the refractive index of the sample to be measured (i.e., the sensing area) Is the refractive index of the sensor chip.

For example, Based on the fixed MREs in the polymer matrix and the sensor chip is a high index of refraction plastic ), The SPR angle is based on the equation (5). In other words, . As seen from equation (5) The In each range. Value may be reduced to a threshold value for collective reflection between the substrate and the sensing area, and the sensing area may have a refractive index Lt; RTI ID = 0.0 > nanometers < / RTI > thickness as a single dielectric disposed between the substrate and the metal layer. Due to the dielectric layer, There is excitation in the range of the long SP with a value of 10, but in the case of the normal (short range) SP 10 Considering the relatively wider 300 Thereby expanding the space. The available materials used as the intermediate layer has a _{MgF 2, CaF 2, AlF 3} , BaF 2 and Na ₅ Al ₃ F _14.

Two or more sensing areas are illuminated because RDOEs focus the tube beam onto one line on the SPR metal film. For example, if the width of the light beam is 1 mm and each sensing area is 50 Leave space for 200 , The sensing area comprising the four elements will be illuminated by one light beam. One of the sensing areas acts as a reference area, which is responsive to unspecified changes due to temperature, pressure, aging, refractive index of the analyte, substrate expansion, and other disturbances in the environment. The other sensing areas on the top of the SPR metal film are located at the top of the SPR metal layer ~ 0.3 - One Lt; RTI ID = 0.0 > MREs. ≪ / RTI > Applicable substrate compounds include polysaccharides or carboxymethyl derivatives such as hydrogel, agarose, dextran, caragen, alginic acid, starch, cellulose, or poly (vinyl alcohol) , Poly (vinyl chloride), polyacrylic acid, polyacrylamides, and organic polymers such as polyethylene glycols.

For example, MREs are ionophores and chloride ionophores, either of which are fixed through a hydrophobic force in a sustained-release polymer matrix or copolymerized in a polymer matrix. The ion-permeable carrier serves as a selective recognition element for a specific ion or neutral ion chemical compound (i.e., an analyte). In order to maintain the electrical neutrality inside the polymer substrate, the binding of the analyte by the ion-permeable carrier coextracts with the ion exchange of the second ionic species (usually both) ). The refractive index of the substrate given by the Kramer-Kronicht transformation ( ) Corresponding changes in equation (5) To change the SPR signal. Maximum operating wavelength Lt; RTI ID = 0.0 > 100 nm, < / RTI > This small ≪ / RTI > Lt; RTI ID = 0.0 > SPR < / RTI > response, Wow Can be determined from the response. In the case of a typical chloride ion carrier such as ETH 5294, The maximum value occurs in the wavelength range of 500 to 700 nm. Thus, the preferred wavelength of light is 670 - 850 nm, where light emitting many general purpose semiconductor lasers and diodes provides light emission.

Other MREs that may be utilized include antigens / antibodies and this SPR sensor can be used as a label-free immune sensor based on antigen / antibody reactions to determine specific analytes. The antibody can be readily immobilized in the hydrogel through a covalent bond. In the Biosensor group from BIAcore, antibodies were immobilized in a carboxymethyl-dextran hydrogel substrate on gold film of SPR sensor to detect various biological compounds. An alternative to the antigen / antibody reaction is the molecular imprinting technique, where synthetic polymers have selective molecular recognition properties. This is due to the positioning of the self-assembled or preformed functional group, which creates a recognition site within the complementary polymer matrix for the shape and functional groups of the analyte. A second alternative is to use oligonucleotide ligands, which can provide specific and high affinity with specific analytes.

Another application example of the present invention is DNA mixture analysis. On a sensor-chip, probes originating from a large array of oligonucleic acid or cDNA libraries can be fabricated utilizing techniques such as, for example, photomicrograph synthesis or high-speed robotics. Depending on the application, such an arrangement may be comprised of several tens to 10 ⁶ sizes per square centimeter (/ cm ² ).

Traditionally, detection schemes have been performed by utilizing fluorescence labeling to detect hybridized patterns of target DNA using confocal optical microscopy. According to the present invention, the mixing reaction of a plurality of sensing regions (in this case, the probe region) can be detected by checking the change of the SPR curve for each sensing region.

Claims (49)

A surface plasmon resonance sensor comprising a first unit and a second unit, wherein the first unit and the second unit are separable, - a first housing, A film made of an electrically conductive material adapted to support surface plasmons, the film being a film held by a first outer surface portion of the first housing, Optical input means located on the second outer surface portion of the first housing for receiving an optical light beam from the second unit, Optical output means located on the third outer surface portion of the first housing to transmit the optical light beam to the second unit, A first set of optical elements adapted to direct the received optical light beam from the first unit to an electrically conductive film, - a second set of optical elements adapted to direct the optical light beam from the electrically conductive film to the optical output means and to transmit the optical light beam from the electrically conductive film to the second unit, The second unit comprising: - a second housing, Means for emitting an optical light beam, A first set of optical elements adapted to prepare an emitted optical light beam, Optical output means located on the first outer surface portion of the second housing for delivering the prepared optical light beam to the first unit, Optical input means located on the second outer surface portion of the second housing to receive the optical light beam from the first unit, Detection means adapted to detect an optical light beam received from the first unit, A second set of optical elements adapted to direct the received optical light beam from the first unit to the detection means, Since the propagation direction of the optical light beam at the position of the optical input means and the optical output means is essentially perpendicular to the outer surface portion of the first housing and the second housing, And the refraction of the light beam is excluded. The surface plasmon resonance sensor according to claim 1, wherein the emitting means is composed of a laser source such as a semiconductor laser diode. 2. The surface plasmon resonance sensor according to claim 1, wherein the emission means comprises a light source emitting light at a single wavelength which is essentially one. The surface plasmon resonance sensor according to claim 1, wherein the emitting means comprises a light source emitting light at a plurality of wavelengths, such as a light emitting diode. The surface plasmon resonance sensor according to any one of the preceding claims, wherein the first set of optical elements of the second unit comprises means for collimating the emitted optical light beam. The surface plasmon resonance sensor according to claim 5, further comprising means for polarizing the optical light beam emitted to the first set of optical elements of the second unit. The surface plasmon resonance sensor according to any one of the preceding claims, wherein the input and output means of the first unit and the second unit are comprised of semi-reflective coating. The surface plasmon resonance sensor according to any one of the preceding claims, wherein the detection means consists of an arrangement of light-sensitive elements such as a multi-photodetector array, a charge coupled device or an auxiliary metal-oxide semiconductor image sensor. The surface plasmon sensor according to any one of the preceding claims, wherein a light protection element is additionally constituted in the sensor. 7. A method according to any one of the preceding claims, wherein the first set of first units comprises a diffractive element such as a diffractive grating or a holographic grating, the diffractive element comprising a collimated collimated optical light beam, Wherein the surface plasmon resonance sensor is adapted to convert the light into a light beam. A method as claimed in any one of the preceding claims, wherein the second set of optical elements of the first unit are constructed of diffractive elements such as diffractive gratings or holographic gratings, And the optical path length of the surface plasmon resonance sensor is set to be smaller than the optical path length of the surface plasmon resonance sensor. 10. A method according to any one of the preceding claims, wherein the first set of optical elements of the first unit is comprised of a reflective element such as a diffractive grating or a holographic grating, the reflective element comprising a parallel collimated optical < RTI ID = 0.0 & Wherein the light is converted into an optical light beam focused by a beam. 10. A method according to any one of the preceding claims, wherein the second set of optical elements of the first unit is comprised of a reflective element, such as a diffractive grating or a holographic grating, To a collimated collimated optical light beam. ≪ Desc / Clms Page number 13 > 10. A surface plasmon resonance sensor according to any one of the preceding claims, wherein the second set of optical elements is comprised of a reflective element such as a reflector. The surface plasmon resonance sensor according to any one of the preceding claims, wherein the electrically conductive film is a metal film such as a gold film, a silver film, an aluminum film, or a titanium film. The surface plasmon resonance sensor according to claim 15, wherein the electrically conductive film is composed of a plurality of electrically conductive films, and the plurality of films are arranged in a pattern extending in the transverse direction. 16. A surface plasmon resonance sensor according to any one of claims 1 to 15, further comprising one layer of dielectric material positioned between the electrically conductive film and the first outer surface portion of the first housing. 17. The surface plasmon resonance sensor of claim 16, further comprising a layer of dielectric material disposed between each of the plurality of electrically conductive films and the first outer surface portion of the first housing. Wherein the moving means are adapted to move the first unit and the second unit with respect to each other and are adapted to move the optical light beam around an electrically conductive film. ≪ RTI ID = 0.0 > And the focus is moved. 19. Apparatus according to any one of the preceding claims, characterized in that a moving means is additionally constituted, the moving means being adapted to move the first unit and the second unit with respect to each other so that the tilt angle of the optical light beam is electrically Wherein the surface plasmon resonance sensor is adapted to change the orientation of the conductive film toward the conductive film. 21. The method of any one of claims 1 to 20, wherein two or more surface plasmon resonance sensors are combined, and the combination of the two or more surface plasmon resonance sensors is arranged in an extended pattern in the transverse direction Wherein the surface plasmon resonance sensor comprises: A method of determining a biological / chemical composition of a sample using a surface plasmon resonance sensor, the surface plasmon resonance sensor comprising a first unit and a second unit, wherein the first unit and the second unit are separable, 1 unit, - a first housing, A film made of an electrically conductive material adapted to support surface plasmons, the film being a film held by a first outer surface portion of the first housing, Optical input means located on the second outer surface portion of the first housing and adapted to receive an optical light beam from the second unit, Optical output means located on the third outer surface portion of the first housing for transmitting the optical light beam to the second unit, A first set of optical elements adapted to direct the received optical light beam from the first unit to an electrically conductive film, A second set of optical elements for directing an optical light beam from an electrically conductive film to an optical output element from an electrically conductive film to an optical light beam, The second unit comprising: - a second housing, Means for emitting an optical light beam, A first set of optical elements adapted to prepare an emitted optical light beam, Optical output means located on the first outer surface portion of the second housing for transmitting the prepared optical light beam to the first unit, Optical input means located in the second outer surface portion of the second housing and receiving from the first unit into the optical light beam, Detection means adapted to detect an optical light beam received from the first unit, A second set of optical elements adapted to direct the received optical light beam from the first unit to the detection means, The propagation direction of the optical light beam at the position of the optical input means and the output means is essentially perpendicular to the outer surface portion of the first housing and the second housing so that when the optical light beam enters the first unit and the second unit, ≪ / RTI > wherein the refraction of the beam is excluded. 1. A surface plasmon resonance sensor comprising a first unit, the first unit comprising: - a first housing, A layer of electrically conductive material adapted to support surface plasmons, said layer being a layer which is maintained by a first outer surface portion of the first housing, Optical input means located on a second outer surface of the first housing, the optical input means comprising optical input means adapted to receive an optical light beam, An optical output means located on a third outer surface of the first housing, the optical output means comprising optical output means adapted to transmit an optical light beam, A first diffractive optical element adapted to direct the received optical light beam to an electrically conductive layer, A first diffractive optical element adapted to direct the reflected optical light beam from the electrically conductive layer to the optical output means, Characterized in that the propagation direction of the optical light beam at the position of the optical input and output means essentially eliminates the refraction of the optical light beam at the position of the optical input and output means perpendicular to the outer surface portion of the first housing sensor. 24. The apparatus of claim 23, wherein the second unit is further configured, - a second housing, Means for emitting an optical light beam, A set of optical elements adapted to prepare the emitted optical light beam, Optical output means located on a first outer surface portion of a second housing, said optical output means comprising optical output means adapted to transmit a prepared optical light beam to a first unit, Optical input means located on a second outer surface portion of the second housing, the optical input means comprising optical input means adapted to receive an optical light beam from the first unit, - detection means adapted to detect an optical light beam received from the first unit, Characterized in that the propagation direction of the optical light beam at the location of the optical input means and the optical output means is essentially perpendicular to the outer surface portion of the second housing to exclude the refraction of the optical light beam at the location of the optical input and optical output means Surface plasmon resonance sensor. 25. The surface plasmon resonance sensor according to claim 24, wherein an optical element adapted to direct the received optical light beam from the first unit to the detection means is further configured in the second unit. The surface plasmon resonance sensor according to any one of claims 24 to 25, wherein the light emitting means is constituted by a laser source such as a semiconductor laser diode. 27. The surface plasmon resonance sensor according to any one of claims 24 to 26, wherein the light emitting means is composed of a light source emitting light at a single wavelength which is essentially one. The surface plasmon resonance sensor according to any one of claims 24 to 25, wherein the light emitting means comprises a light source emitting light at a plurality of wavelengths as one light emitting diode. 29. A surface plasmon resonance sensor according to any one of claims 24 to 28, characterized in that the optical element set of the second unit comprises means for parallel collimation of the emitted optical light beam. 30. The surface plasmon resonance sensor according to claim 29, further comprising means for polarizing the optical light beam emitted to the optical element set of the second unit. The surface plasmon resonance sensor according to any one of claims 23 to 30, wherein the input and output means of the first unit and the second unit are constituted by anti-reflective coating. The surface plasmon resonance device according to any one of claims 24 to 31, characterized in that the detection means consists of an array of light sensitive elements, such as a multi-optical detection arrangement, a charge coupled device, or an auxiliary metal- sensor. The surface plasmon resonance sensor according to any one of claims 23 to 32, wherein the first diffractive optical element and the second diffractive optical element of the first unit are composed of optical gratings such as a reflective holographic grating. The surface plasmon resonance sensor according to any one of claims 23 to 33, wherein the electrically conductive film is a metal film such as a gold film, a silver film, an aluminum film, or a titanium film. 35. The surface plasmon resonance sensor as claimed in claim 34, wherein the electrically conductive film is composed of a plurality of electrically conductive films, and the plurality of films are arranged in an extended pattern in the transverse direction. The surface plasmon resonance sensor according to any one of claims 23 to 35, further comprising one layer of dielectric material positioned between the electrically conductive film and the first outer surface portion of the first housing. 37. The surface plasmon resonance sensor of claim 35, further comprising a layer of dielectric material disposed between each of the plurality of electrically conductive films and the first outer surface portion of the first housing. 37. A device according to any one of claims 23 to 37, characterized in that the moving means are further configured and the moving means are adapted to move the first unit and the second unit with respect to each other and are movable about one or more electrically conductive films And moving the focus of the optical light beam. 37. A device according to any one of claims 23 to 37, further comprising a moving means, said moving means being adapted to move the first unit and the second unit with respect to each other so that the tilt angle of the optical light beam is changed one or more electrically Wherein the surface plasmon resonance sensor is adapted to change the orientation of the conductive film toward the conductive film. As a surface plasmon resonance sensor, - transparent components, A layer of an electrically conductive material adapted to support a surface plasmon, said layer comprising one layer of an electrically conductive material, A first optical grating adapted to direct the received optical light beam held by the first outer surface portion of the component to an electrically conductive layer, the propagation direction of the received optical light beam at the position of the first optical grating being The optical light beam received essentially perpendicular to the first outer surface of the component comprises a first optical grating that is actually collimated, - adapted to receive an optical light beam from an electrically conductive layer and to re-emit an optical light beam from an electrically conductive layer, the second optical grating being held by a second outer surface portion of the component, Characterized in that the propagation direction of the re-emitted optical light beam at the position is essentially perpendicular to the second outer surface portion of the element and the re-emitted optical light beam is constituted by a substantially parallel collimated second optical grating Surface plasmon resonance sensor. 41. The method of claim 40, Means for emitting an optical light beam, A set of optical elements adapted to prepare the emitted optical light beam, - means for detecting the re-emitted optical light beam is additionally constituted. 42. The surface plasmon resonance sensor according to claim 41, further comprising an optical element adapted to direct the re-emitted optical light beam to the detection means. The surface plasmon resonance sensor according to any one of claims 41 to 42, wherein the light emitting means is constituted by a laser source such as a semiconductor laser diode. 44. The surface plasmon resonance sensor according to any one of claims 41 to 43, wherein the light emitting means is composed of a light source emitting light at a single wavelength which is essentially one. 43. The surface plasmon resonance sensor according to any one of claims 41 to 42, wherein the light emitting means comprises a light source emitting light at a plurality of wavelengths, such as one light emitting diode. 46. A surface plasmon resonance sensor according to any one of claims 41 to 45, characterized in that the optical element set is constituted by means for collimating the emitted optical light beam. 47. The surface plasmon resonance sensor of claim 46, further comprising means for polarizing the emitted optical light beam in the set of optical elements. 47. The surface plasmon resonance sensor according to any one of claims 41 to 47, wherein the detection means is composed of an arrangement of light-sensitive elements such as a multi-optical detection arrangement, a charge coupled device or an auxiliary metal-oxide semiconductor image sensor. 49. The surface plasmon resonance sensor according to any one of claims 40 to 48, wherein the electrically conductive film is composed of a metal film such as a gold film, a silver film, an aluminum film or a titanium film.