JPH1151857A - Surface plasmon sensor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a surface plasmon sensor in which two-dimensional scanning can be carried out over a wide range through a simple structure. SOLUTION: In the surface plasmon sensor, a coupler means 10 is provided with a sensor attachment 15 extending in the X direction and a sensor unit 1 is supported by the sensor attachment 15 while keeping a constant spacing, being filled with a refractive index matching oil 9, between the sensor unit 1 and the coupler means 10. The sensor unit 1 movable in the X direction along the sensor attachment 15 is moved in the X direction by means of a carrying shaft 6 secured to the sensor unit 1. A light source optical means is provided with a telecentric scanner and two-dimensional scanning is carried out by translating the incident position of a light beam L to the coupler means 10 perpendicularly to the moving direction of the sensor unit 1.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a surface plasmon sensor for quantitatively analyzing a substance in a sample by utilizing the generation of surface plasmons, and more particularly, to a measurement method using one-dimensional or two-dimensional scanning. It relates to a surface plasmon sensor.

[0002]

2. Description of the Related Art In a metal, free electrons vibrate collectively to generate a compression wave called a plasma wave. And, the quantization of this compression wave generated on the metal surface is
It is called surface plasmon.

Hitherto, various surface plasmon sensors for quantitatively analyzing a substance in a sample by utilizing the phenomenon that surface plasmons are excited by light waves have been proposed. And among the most well-known of them are:
A system using a system called a Kretschmann configuration is mentioned (for example, see JP-A-6-167443).

A surface plasmon sensor using the above system basically includes a prism, a metal film formed on one surface of the prism and brought into contact with a sample, a light source for generating a light beam, and a light source for applying the light beam to the prism. An optical system which passes through the interface between the prism and the metal film so as to obtain various angles of incidence, and a light which can detect the intensity of the light beam totally reflected at the interface at various angles of incidence. And a detecting means.

In order to obtain various angles of incidence as described above, a so-called goniometer (see, for example, JP-A-6-50882) for rotating a light beam irradiation system is used, or various types of light beams are used. An optical system is used in which a relatively thick light beam is incident so as to be focused at the interface so that a component incident at an angle is included. In the former case, the light beam whose reflection angle changes with the deflection of the light beam is detected by a small photodetector that moves synchronously with the deflection of the light beam, or by an area sensor that extends along the direction of change in the reflection angle. Can be detected. On the other hand, the latter case can be detected by an area sensor extending in a direction in which all light beams reflected at various reflection angles can be received.

When a light beam is incident on a metal film at an incident angle θ equal to or larger than the total reflection angle, a “smear wave” called an evanescent wave is generated in the metal film on the reflection surface. The evanescent wave has an electric field distribution in the sample in contact with the metal film, and surface plasmons are generated at the interface between the metal film and the sample. When the wave vector of the evanescent wave generated by the incidence of the p-polarized light beam on the metal film is equal to the wave vector of the above-described surface plasmon and the wave number matching is established, both are in a resonance state, and the light energy is changed to the surface plasmon. The plasmon is excited by the migration. At this time, the intensity of the totally reflected light is significantly reduced due to the transfer of light energy.

Therefore, in the above-mentioned surface plasmon sensor, the intensity of the light beam totally reflected by the metal film is measured for the light beam incident on the metal film at various incident angles θ, so that the reflection is performed. An incident angle θ _sp (total reflection elimination angle) at which a phenomenon in which the intensity significantly decreases occurs, and the total reflection elimination angle θ _sp and the wave number vector K _{1 of the} incident light are obtained.
, The resonance wave number K _sp is derived from the relationship K _sp = K ₁ sin θ _sp . When the wave number K _{sp of the} surface plasmon is known, the dielectric constant of the sample is obtained. That is, assuming that the angular frequency of the surface plasmon is ω, the speed of light in a vacuum is c, and the dielectric constants of a metal and a sample are ε _m and ε _s , respectively, the following relationship is obtained.

[0008]

(Equation 1)

[0009] Knowing the dielectric constant epsilon _s of the sample, since it is found the concentration of a specific substance in the sample based on a predetermined calibration curve or the like, after all, the total reflection overcome angle the reflected light intensity decreases theta _sp
, A specific substance in the sample can be quantitatively analyzed.

[0010]

In the physical property analysis using a surface plasmon sensor, there are cases where it is desired to measure a plurality of samples under the same conditions, or to obtain two-dimensional physical property information of the samples.

However, in the above-described conventional surface plasmon sensor, it is difficult to perform beam scanning over a wide range, and measurement is limited to a narrow range.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a surface plasmon sensor capable of performing one-dimensional or two-dimensional scanning over a wide range with a simple configuration.

[0013]

The surface plasmon sensor of the present invention comprises a transparent substrate having a predetermined refractive index, and
A sensor unit including a metal film disposed on one surface side of the transparent substrate, and having the same refractive index as the predetermined refractive index on another surface side of the transparent substrate opposite to the one surface. Coupling means arranged with a refractive index matching liquid interposed therebetween, transmitting a light beam incident from an input portion formed in a part thereof, and allowing the light beam to enter an interface between the transparent substrate and the metal film, Coupler means that transmits a light beam totally reflected at the interface and exits from an output portion formed in another portion, and a portion through which the light beam is transmitted has substantially the same refractive index as the predetermined refractive index. A surface plasmon sensor for detecting the intensity of the light beam emitted from the output portion, wherein the light beam is incident from the input portion and totally reflected at the interface and emitted from the output portion.
Sensor supporting means for supporting the distance between the transparent substrate and the coupler means so as to be always constant, wherein the distance is filled with the refractive index matching liquid, and a light beam is applied to the interface in a predetermined direction at the interface. Incident position moving means for moving the incident position in the input portion of the light beam so as to be sequentially incident on different locations under the same incident condition, or the sensor unit in a predetermined direction with the interval being constant,
At least one of a sensor unit relative moving means for moving the sensor unit relatively to the coupler means is further provided.

In the above, both the incident position moving means and the sensor unit relative moving means are provided, and a predetermined direction in the incident position moving means and a direction in which the predetermined direction in the sensor unit relative moving means intersect each other. It is desirable to do.

The "incident position moving means" may be, for example, a telecentric scanning optical system in which an incident position is moved by deflecting a light beam by a light source optical means having a galvanometer mirror or the like. Alternatively, the incident position may be moved by mechanically moving the light source optical means itself.

Further, the "sensor unit relative moving means for relatively moving with respect to the coupler means" includes:
In addition to the moving unit that moves the sensor unit itself, a unit that fixes the sensor unit and moves the coupler unit side may be used.

[0017] The sensor support means may be fixedly provided on a part of the coupler means, for example. Further, light source optical means for emitting a light beam and allowing the light beam to enter the input section, detection means for detecting the intensity of the light beam emitted from the output section, and the coupler means are fixed on a base. The sensor unit is movably supported by the support means with respect to the coupler means,
The sensor unit relative moving means may move the sensor unit. Alternatively, the sensor support means is fixed on a base, the sensor unit is fixedly supported by the sensor support means, and a light source optical means for emitting a light beam and causing the light beam to enter the input unit; An optical system unit including a detecting unit for detecting the intensity of the light beam emitted from the output unit and the coupler unit is movably disposed on the base with respect to the sensor unit, and the relative movement of the sensor unit is provided. The means may move the optical system unit.

Further, the sensor support means is fixed on a base, the sensor unit is movably supported by the sensor support means with respect to the coupler means, and the sensor unit relative movement means is provided by the sensor unit. Optical light source means for causing a light beam to be incident on the input section, detection means optical means for guiding the light beam to a detection means for detecting the intensity of the light beam emitted from the output section, and An optical unit including the coupler means is disposed on the base, or the sensor unit is fixedly supported by the sensor support means, and the optical system unit moves on the base with respect to the sensor unit. The sensor unit relative moving means is provided so as to move the optical system unit, A light source and the detection means for emitting a beam, may be separately removably disposed in said optical unit on the base.

The sensor support means is fixed on a base, the sensor unit is movably supported by the sensor support means with respect to the coupler means, and the sensor unit relative movement means comprises An optical unit including an optical light source unit for causing a light beam to enter the input unit, a detecting unit for detecting the intensity of the light beam emitted from the output unit, and an optical unit including the coupler unit. Or the sensor unit is fixedly supported by the sensor support means, and the optical system unit is movably disposed on the base with respect to the sensor unit, and the sensor unit relative movement means Is for moving the optical system unit, and a light source for emitting the light beam is provided outside the base. It stands to may be arranged. In this case, an optical fiber for guiding the light beam emitted from the light source to the optical device may be provided. Further, it is desirable that the optical fiber be of a polarization-maintaining type.

Further, for filling the gap with the refractive index matching liquid, a matching liquid supply means for supplying the refractive index matching liquid to the gap, and the refractive index matching liquid is provided on the other surface of the transparent substrate. A space portion that can penetrate to a higher position, and communicates with the space, the matching liquid supply means may fill the space with the refractive index matching liquid, or the coupler means On the side facing the transparent substrate, a reservoir for storing the refractive index matching liquid is formed, a waterproof wall is provided on the transparent substrate so as to surround the metal film, and the sensor unit is disposed on the reservoir. A state in which the other surface of the transparent substrate is supported in a state of being immersed in the refractive index matching liquid, and the gap is filled with the refractive index matching liquid. It may be.

As the input part and the output part of the coupler means, a prism may be provided in the coupler means, and the input part and the output part may be formed in the prism, or the input part and the output part may be formed. The portion may be formed by a diffraction grating. Alternatively, the coupler means has a convex portion on the side of the coupler means opposite to the side facing the transparent substrate, and one side surface of the convex portion and the other side surface facing the one side are formed of a transparent plate. And the inside of the convex portion may be filled with the refractive index matching liquid, and the one side surface and the other side surface may be the input portion and the output portion, respectively.

Here, "coupler means" is a general term for means for coupling a light beam incident on the interface to conditions for generating surface plasmon resonance.

The transparent substrate of the sensor unit is
Consisting of a main transparent substrate and a holding transparent substrate, the metal film is arranged on the main transparent substrate, and the holding transparent substrate is arranged to face the coupler means via the refractive index matching liquid. Good. Further, the transparent substrate of the sensor unit may be composed of a holding substrate and a plurality of main transparent substrates arranged on the holding substrate, and a metal film may be formed on each main transparent substrate. At this time, the main transparent substrates may have different substrate sizes.
As described above, when the transparent substrate of the sensor unit includes one or more main transparent substrates and the holding transparent substrate, the main transparent substrate and the holding transparent substrate have a refractive index substantially equal to the predetermined refractive index. It is desirable that they are brought into close contact with each other via a refractive index matching liquid having the following formula: Further, it is desirable that the main transparent substrate be easily detachable from the holding transparent substrate.

It should be noted that a binding reaction film may be provided on the metal film, and a specific substance that reacts with the binding reaction film may be detected. Here, the “binding reaction membrane” and the “specific substance that reacts with the binding reaction membrane” are, for example, an antigen (antibody) and an antibody (antigen) that cause an antigen-antibody reaction. It may be. When there are a plurality of main transparent substrates, a bonding reaction film may be formed on each metal film on each main transparent substrate. The same type of binding reaction film, for example, a binding reaction film composed of the same antibody (antigen) may be formed on each metal film, or a different type of binding reaction film, for example, a different antibody (antigen) may be formed for each metal film. ) May be formed. Further, a plurality of the same or different types of bonding reaction films may be formed on different portions on a single metal film. When a sensor unit having a plurality of different types of binding reaction membranes (binding reaction membranes composed of different antigens (antibodies)) is used, different phenomena in each binding reaction membrane are sequentially measured for a single sample. Is also good.

[0025]

According to the surface plasmon sensor of the present invention, a sensor unit comprising a transparent substrate and a metal film disposed on one surface side of the transparent substrate and brought into contact with a sample is provided.
The distance between the transparent substrate and the coupler means is supported by the sensor supporting means so that the distance between the transparent substrate and the coupler means is always constant, and the gap is filled with a refractive index matching liquid. One or both of an incident position moving means for moving the incident position of the light beam at the input portion, and a sensor unit relative moving means for moving the sensor unit in a predetermined direction with the interval being constant. , One-dimensional or two-dimensional scanning becomes possible.

In particular, since the refractive index matching liquid layer is provided between the transparent substrate and the coupler means, relative movement of the sensor unit with respect to the coupler means is easy.

[0027] Further, both the incident position moving means and the sensor unit relative moving means are provided, and a predetermined direction of the incident position moving means and a predetermined direction of the sensor unit relative moving means intersect with each other. A wide range of two-dimensional scanning becomes possible.

Since two-dimensional measurement has become possible,
It is possible to measure secondary physical properties of a sample, and it is also possible to efficiently measure a plurality of samples.

[0029]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 shows one side surface shape of the surface plasmon sensor according to the first embodiment of the present invention. FIGS. 2 and 3 show the plasmon sensor shown in FIG. And the shape viewed from the direction of arrow B. However, FIG. 3 is a partial sectional view.

As shown in the figure, the basic configuration of the surface plasmon sensor is as follows: a sensor unit 1 having a metal film made of gold, silver, etc., which is brought into contact with a sample S to be measured, and a sensor supporting the sensor unit 1. A coupler means provided with a support means for disposing a refractive index matching oil (matching liquid) with respect to the sensor unit; a light beam is generated; and the light beam is made incident on the coupler means. It comprises a light source optical means 20 and a light detecting means 30 for measuring the intensity of a light beam emitted from the coupler means 10.

Next, a detailed configuration of each unit in the first embodiment of the present invention will be described.

In the sensor unit 1, a metal film 3 of gold, silver or the like is formed on a sensor substrate 2 which is a transparent substrate made of glass or the like having a uniform thickness, and a waterproof wall 5 is provided so as to surround the metal film 3. It was done. When the metal film 3 such as gold is formed on the glass substrate 2, chromium is previously arranged on the glass substrate 2 by about 1 nm. This facilitates the formation of the metal film 3 and suppresses peeling.
In the analysis using a surface plasmon sensor,
In general, a binding reaction film (here, an antigen (or an antibody)) is formed on the metal film 3, and an antibody (or an antigen) that specifically adsorbs to the specific reaction using an antigen-antibody reaction that selectively responds to a specific substance. ) The amount is measured as a change in the angle of incidence. Here, the metal film 3 and the bonding reaction film formed on the metal film 3 are integrally called a sensor film. In addition, by using such a sensor unit 1, the distance between the sensor unit and the coupler unit can be reduced even when the sensor is replaced, as compared with the case where the matching liquid is applied and the substrate is directly adhered to the coupler unit. Since it can be easily made constant and delicate adjustment of the film thickness and the like is not required, replacement of the sensor can be easily performed and automation can be performed.

The coupler means 10 comprises a cell 12 made of glass having a recess 11 formed on the side facing the sensor unit 1, and a triangular prism 13 formed on the other surface of the cell 12. It is. The coupler means 10 includes a sensor support means (sensor attachment) 15 for supporting the sensor unit 1 at a part thereof, so that the distance between the sensor substrate 2 and the cell 12 is always constant by the sensor attachment 15. Support the sensor unit 1. Here, the sensor unit 1 is supported by a part of the waterproof wall 5 so that the substrate 2 of the sensor unit 1 is immersed in the matching oil 9 and the positional relationship of the sensor unit 1 with respect to the coupler means 10 is determined. is there. The space between the sensor substrate 2 and the coupler means 10 is filled with a refractive index matching oil 9. As the sensor substrate 2, the coupler means 10, and the refractive index matching oil 9, those having substantially the same refractive index are used. As shown in FIG. 2, the coupler means 10 has a structure extending in one direction, and the sensor attachment 15 is formed along the recess 11. The sensor attachment 15 has a transport rail (not shown), and the sensor unit 1 is movable along the transport rail. The transport shaft 6 is fixed to the sensor unit 1, and the transport shaft 6 is sandwiched between rollers 7.
This is a configuration that can be moved in the direction. That is, in the present embodiment, the sensor unit relative movement means is configured by the transport rail, the transport shaft 6 and the roller 7 provided in the sensor attachment 15.

The light source optical means 20 comprises a light source 21 composed of a semiconductor laser or the like for generating a light beam L, a cylindrical lens 22, and a telecentric scanner 23 which is a light deflecting means utilizing a telecentric optical system. The telecentric scanner 23 includes a cylindrical lens 22
Is composed of a galvanomirror 24 disposed at a focal length position of the lens and two cylindrical lenses 25 and 26. The light beam L emitted from the light source 21 is focused on a galvanometer mirror 24 by a cylindrical lens 22, is reflected by the galvanometer mirror 24, and is incident on a cylindrical lens 25 of a telecentric scanner 23. The light beam L is converted into parallel light by the cylindrical lens 25, and is focused by the cylindrical lens 26 at the interface between the metal film 3 and the sensor substrate 2 in a plane perpendicular to the long axis of the prism 13 and is incident on the prism 13. . The incident position of the light beam L on the prism 13 is translated in the Y direction with the swing of the galvanometer mirror 24. The light source
The light beam L emitted from 21 is prism-converted as p-polarized light.
13, the focused light beam L is
It contains components that enter the interface 4 between the sensor substrate 2 and the metal film 3 at various incident angles θ. The incident angle θ is set to an angle equal to or larger than the total reflection critical angle, and the light beam L
Is totally reflected at the interface 4.

In this embodiment, as described above, the telecentric scanner which is the light deflecting means is used as the light beam incident position moving means. For example, a light source is placed on a stage which can be mechanically moved in the Y direction. It is also possible to use a light source moving unit that disposes and moves the stage to move the light source itself, thereby moving the incident position of the light beam in parallel in the Y direction.

The reflection angle at which the light beam L is reflected from the interface 4 changes in accordance with the change in the angle of incidence of the light beam L on the interface 4. For example, a CCD line sensor or the like having light receiving elements arranged side by side is used. In addition, a photodiode is used as a light detecting means, as described in Japanese Patent Application No. 8-109366.
A divided photodiode, a photodiode array, or the like may be used. However, the arrangement of the light detection means 30 is controlled so that the total reflection beam whose emission position changes with the change of the incident position of the light beam with respect to the prism can always be detected.

Hereinafter, the analysis of a sample by the surface plasmon sensor having the above configuration will be described. First, a plurality of sample cells 8 are arranged on the sensor film, and different samples Sn (S ₁ , S ₂ , S ₃ ,...) Are injected into each cell 8, and each sample is brought into contact with the sensor film. (See FIG. 5). In addition,
FIG. 5B shows a cross section of FIG.

Next, each of the plurality of samples is analyzed. At the time of sample analysis, a light beam L set to p-polarized light for each sample is incident on one surface of the prism 13, passes through the prism 13, and is incident on the interface 4. As described above, the condensed and incident light beam L is incident on the interface 4 between the metal film 3 and the sensor substrate 2 at various incident angles θ. The light beam L is totally reflected at the interface 4, passes through the prism 13 again, and is emitted from the other surface of the prism 13. The emitted light beam L is applied to the light detecting means 30.
Is detected by At this time, the light detection signal output by the light detection means 30 is the intensity I of the totally reflected light beam L.
Is shown for each incident angle θ to the interface 4, and the relationship between the reflected light intensity I and the incident angle θ is substantially as shown in FIG.

Here, the light incident at a specific incident angle (total reflection elimination angle) θ _sp excites surface plasmons at the interface between the metal film 3 and the sample Sn. Declines sharply. Therefore, the total reflection elimination angle θ _sp can be found by using the light detection signal output for each light receiving element of the light detection means 30, and the specific substance in the sample Sn can be determined based on the value of the total reflection elimination angle θ _sp. Quantitative analysis can be performed. The reason is as described in detail above.

In this apparatus, in order to analyze each of a plurality of samples, the sensor unit 1 is intermittently transported in the X direction along the transport rail of the sensor attachment 15, and the light beam L is translated by the telecentric scanner 20. The light is sequentially incident on each sample Sn. In this way, by performing a two-dimensional scan by causing a light beam to be incident on each sample under the same conditions, it is possible to efficiently analyze a plurality of samples in a short time.

Since the light beam can be scanned two-dimensionally as described above, the present apparatus mounts a sample such as a gel sheet used for electrophoresis on the metal film 3 and The present invention can also be used for obtaining two-dimensional physical property information of a substance to be analyzed distributed in a sample by performing two-dimensional scanning.

Further, as shown in FIG.
By setting a plurality of regions 3a and using a sensor film in which a different binding reaction film is formed in each region 3a and performing two-dimensional light beam scanning, different immune reactions and the like generated in each region are performed. Analysis can also be performed for each region.

Next, a second embodiment of the present invention is shown in FIGS. FIG. 7 shows one side surface shape of the surface plasmon sensor according to the second embodiment. FIGS. 8 and 9 show the shape of the plasmon sensor shown in FIG. This is the shape seen from the side. A detailed description of the same configuration and operation as in the first embodiment described above is omitted (the same applies to the following embodiments).

In the second embodiment, pipes 41 and 42 for allowing the matching oil 9 to enter and exit are arranged in the gap between the sensor unit 1 and the coupler means 10 through the cell 12. The end has an opening at a position higher in the vertical direction than the bottom surface of the substrate 2 to form a space in which the matching oil 9 can penetrate to a position higher than the bottom surface of the substrate 2. A pump 44 is disposed in the matching liquid tank 43 for storing the oil 9, and a pump 44 is arranged in the middle thereof, and forms a matching liquid supply unit together with the matching liquid tank 43 and the pump 44.
The sensor unit 1 is not soaked in the matching oil as in the case of the first embodiment described above, but is in a state where the bottom surface of the glass substrate 2 is in contact with the liquid surface of the matching oil 9. .

The sensor unit 1 has a transfer shaft 6 ′ at both ends, and the transfer shaft 6 ′ is formed wide so as to make the recess 11 of the cell 12 filled with the matching oil 9 a closed space. After the sensor unit 1 is supported by the sensor attachment 15, the pump 44 is operated to supply the matching oil 9 between the surfaces from the matching liquid tank 43 through the pipe 42. At this time, by supplying the matching oil 9 until the liquid level of the matching oil 9 entering the one pipe 41 is higher than the bottom surface of the substrate 2, the matching oil 9 can be filled with no gap between the surfaces. it can.

The transport shaft 6 'is provided with rollers 7a' and 7b '.
And the sensor unit 1 is provided with rollers 7a 'and 7b'
It is moved with the rotation of.

In the above embodiment, the case where the coupler means having the prism is used has been described. However, a configuration in which the prism is not used for the coupler means may be adopted.

For example, as shown in FIG. 10 as a third embodiment, diffraction gratings 50 and 51 may be formed in the cell 12 and light beams L may be input and output from the diffraction gratings 50 and 51. . In this case, the light beam L is diffracted by the input diffraction grating 50, enters the interface 4 at an angle θ, is totally reflected by the interface 4, is diffracted by the output diffraction grating 51, and is emitted. Then, the emitted light beam L is detected by the light detecting means 30.

Further, as shown in FIG. 11 as a fourth embodiment, a downwardly convex portion is formed on the lower surface of the cell 12, and the inside of the convex portion 53 is filled with a refractive index matching oil 9, and The glass windows 54 and 55 are formed on the glass window 5
A configuration in which the light beam L is input and output from 4, 55 may be adopted. The glass windows 54 and 55 have the refractive index of the sensor substrate 2.
And the one having substantially the same refractive index as the matching oil 9 is used. In this case, the portions other than the glass windows 54 and 55 of the cell 12 do not need to have transparency.

A fifth embodiment is shown in FIGS. FIG. 12 shows one side surface shape of the surface plasmon sensor according to the fifth embodiment.
The plasmon sensor shown in FIG. 12 has a shape viewed from the direction of arrow A and a shape viewed from the direction of arrow B, respectively. However, in FIGS. 13 and 14, a part of the device is omitted, and a partial cross-sectional view is shown.

In this embodiment, the sensor unit 101
Comprises a sensor unit 104 including a transparent substrate 102 and a metal film 103 disposed on the transparent substrate 102, and a sensor holding unit 105 that holds the sensor unit 104. Sensor holder 105
Is formed of a transparent member 106 having the same refractive index as that of the transparent substrate 102 of the sensor section 104. The transparent substrate 102 of the sensor section 104 is brought into close contact with the transparent member 106 via a matching oil. Is measured. It is assumed that a bonding reaction film is formed on the metal film 103 as in the above-described embodiment. In order to replace the sensor, the sensor unit 101 may be replaced, or the sensor unit 104 may be replaced.
Only one may be replaced. The sensor unit 104 has a simple configuration, so it is inexpensive and easy to replace. In addition, a sensor of a free form that does not use a substrate of a uniform size
Can be used as As shown in FIG. 15, a plurality of sensor units 104 'of the same or different sizes are arranged in the sensor holding unit 105, and different samples Sn (S1, S2, S3,...) Are provided on each of the sensor units 104'. ) Hold each sample Sn
May be sequentially measured. At this time, the bonding reaction film a is formed on the metal film 103 of each sensor 104 '.
Are formed, and the sample is placed on each of the binding reaction films a. Further, as shown in FIG.
On the 4 ″ metal film 103, binding reaction films a, b, c, d,.
May be measured sequentially in each of the bonding reaction films a, b, c, d,.

In the coupler means 110, similarly to the fourth embodiment, a downwardly convex portion is formed in a part of the cell 112, and glass windows 114, 114 formed on the side surfaces of the convex upper portion 113 are formed.
A component that allows a light beam to enter and exit from 115 is used. At the time of measurement, the cell 112 and a housing for an optical system described later are used.
141 Fill the recess surrounded by and with matching oil 9,
The lower surface of the sensor holding portion 105 is soaked in the matching oil 9.

The light beam L is emitted and the coupler means 110
The light source optical means 120 is provided with a light source 121 such as a semiconductor laser and a collimator lens 122 and emits parallel light, and a telecentric scanner 124 which is a light deflecting means using a telecentric optical system. The telecentric scanner 124 includes a galvanometer mirror 125 and an fθ lens 126. f
The light beam L is focused into a spot by the θ lens 126 and is incident from the window 114 of the coupler means 110. The incident position of the light beam L on the window 114 is translated in the Y direction with the swing of the galvanometer mirror 125. The light beam L emitted from the light source device 123 is p
The light beam L which is incident on the coupler means 110 as polarized light is focused on the transparent substrate 102 and the metal film 10.
3 includes components that enter the interface 107 at various angles of incidence θ. The incident angle θ is set to an angle equal to or greater than the critical angle for total reflection so that the light beam L is totally reflected at the interface 107.

An fθ lens 131 is also provided on the detection means 130 side for detecting the light beam reflected from the interface 107 and output from the window 115 of the coupler means 110, and the light beam is always detected by the detection means 130. It is configured to be.

The above-mentioned coupler means 110 and light source optical means
120 and the detection means 130 are all arranged on the base 140. A coupler means 110 is fixed to an optical system casing 141 formed on the base 140 so as to surround the light source optical means 120 and the like, and the fθ lens 126 and the detection means 130 side of the light source optical means 120 are provided. lens 131 is supported by the lower surface of the coupler means 110.

On the base 140, an optical system housing 141 is further provided.
A housing 142 is formed so as to surround the sensor unit 101.
A transport rail 143 extending in the direction is provided. The housing 142 and the transport rail 143 are also sensor attachments that support the sensor unit 101 so that the distance between the sensor unit 101 and the coupler means 110 is always constant. The sensor unit 101 is coupled along the transport rail 143 with the coupler. It is possible to move in the X direction while keeping the distance from the means 110 constant. That is, in the present embodiment, the transport rail 143 provided on the base corresponds to the sensor unit relative moving means.

As described above, the surface plasmon sensor according to the present embodiment includes the movement of the sensor unit 101 in the X direction and the movement of the telecentric scanner 12 of the light source optical means 120.
The two-dimensional scanning can be performed by moving the incident position of the light beam in the Y direction by the step (4).

FIG. 17 shows a sixth embodiment of the present invention.
Shown in In the sixth embodiment, the same sensor unit 101 and coupler means 11 as those in the fifth embodiment are used.
0, light source optical means 120 and detection means 130 are used. The light source optical means 120 and the detection means 130 are arranged on a carrier 145, and the coupler means 11 is mounted on an optical system housing 146 formed so as to surround the light source optical means 120 and the like on the carrier 145.
0 is fixed, and the fθ lens 12
The fθ lens 131 is supported by the lower surface of the coupler means 110 on the side of the detecting means 130 and the detecting means 130.

The transfer table 145 is further mounted on a transfer rail 148 extending on the base 147 and extending in the X direction, and is movable along the transfer rail 148 in the X direction. The movement of the carriage 145 in the X direction means that
This means that the light source optical means 120 moves in the X direction. With this movement, the incident position of the light beam L on the interface 107 becomes X
It will be moved in the direction. In addition, the housing 1 is further placed on the base 147 so as to surround the optical system housing 146.
A sensor unit 101 is fixedly provided on the upper surface of the housing 149. That is, the housing 149 also functions as a sensor attachment that supports the sensor unit 101. Note that a sample supply unit 150 for supplying a sample S as an object to be detected is attached to the sensor unit 124.

As described above, the surface plasmon sensor of the present embodiment has two movements by the movement of the carriage 145 in the X direction and the movement of the light beam incident position in the Y direction by the telecentric scanner 124 of the light source optical means 120. A dimensional scan can be performed.

FIG. 18 shows a seventh embodiment of the present invention.
And FIG. FIG. 19 shows a side surface shape of the surface plasmon sensor according to the seventh embodiment, and FIG. 19 shows a shape of the plasmon sensor shown in FIG. However, in FIG. 19, a part of the device is omitted, and a partial cross-sectional view is shown.

The present embodiment has a two-dimensional scanning mechanism similar to that of the above-described sixth embodiment. However, a light source device 123 comprising a light source 121 such as a semiconductor laser and a collimator lens 122 and a detecting means 130 are provided in a housing. It differs from the sixth embodiment in that it is mounted outside the body 149. That is,
In the present embodiment, the light beam L is transmitted to the coupler means 11.
In order to make the light beam incident on the light source device 123, a light source optical means 128 having a mirror 127 and a telecentric scanner 124 for reflecting and polarizing the light beam L from the light source device 123, and a light beam output from the coupler means 110 are guided to the detecting means 130 A lens 132 and optical means 135 for detecting means having mirrors 133 and 134 are housed in an optical housing 146, and a light source device 123 is provided.
The detecting means 130 is provided outside the housing 149.

The light source 121 and the detecting means 130 are exchanged according to the object to be measured and the desired measurement accuracy.
If a more accurate measurement is to be performed using a CD, it is detachable because a two-segment photodiode is used as the detection means. Easy.

Further, the light source and the detecting means are connected to the optical housing 146.
In order to be provided inside, the configuration must be limited because the device must be arranged in a limited space. However, since the device can be mounted outside, a free configuration can be adopted without such restrictions. For example, a plurality of light sources and detection means can be attached.

Further, a light source made of a semiconductor laser or the like is arranged independently of the optical housing 146 and the base 147 on which the housing 149 is installed, and a light beam emitted from the light source is transmitted through an optical fiber, especially A configuration may be adopted in which the polarization-maintaining optical fiber is used to guide light to the light source optical unit.

The plasmon sensor according to the fourth embodiment shown in FIG. 12 also has a configuration in which the light source and the detection means are mounted outside the housing 142 in the same manner as the seventh embodiment, and the light source is independently provided. A light beam from the light source can be arranged to be guided to the light source optical means by an optical fiber.

As a surface plasmon sensor according to another embodiment, a sensor unit relative moving means,
A surface plasmon sensor that includes only one of the incident position moving means and analyzes a plurality of samples arranged in a one-dimensional direction may be used.

[Brief description of the drawings]

FIG. 1 is a side view of a surface plasmon sensor according to a first embodiment of the present invention.

FIG. 2 is a view of the surface plasmon sensor shown in FIG.

FIG. 3 is a view of the surface plasmon sensor shown in FIG.

FIG. 4 is a graph showing a schematic relationship between an incident angle of a light beam in a surface plasmon sensor and a light intensity detected by a light detecting unit.

FIG. 5 is a diagram showing a multi-channel type sensor;

FIG. 6 is a diagram showing a sensor film divided into a plurality of regions.

FIG. 7 is a side view of a surface plasmon sensor according to a second embodiment of the present invention.

FIG. 8 is a view of the surface plasmon sensor shown in FIG.

FIG. 9 is a view of the surface plasmon sensor shown in FIG.

FIG. 10 is a side view of a surface plasmon sensor according to a third embodiment of the present invention.

FIG. 11 is a side view of a surface plasmon sensor according to a fourth embodiment of the present invention.

FIG. 12 is a side view of a surface plasmon sensor according to a fifth embodiment of the present invention.

FIG. 13 is a view of the surface plasmon sensor shown in FIG.

FIG. 14 is a view of the surface plasmon sensor shown in FIG.

FIG. 15 is a diagram illustrating a surface plasmon sensor having a plurality of sensor units.

FIG. 16 is a diagram illustrating a surface plasmon sensor having a plurality of sensor units on which different binding reaction films are formed.

FIG. 17 is a side view of a surface plasmon sensor according to a sixth embodiment of the present invention.

FIG. 18 is a side view of a surface plasmon sensor according to a seventh embodiment of the present invention.

FIG. 19 is a view of the surface plasmon sensor shown in FIG.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Sensor unit 2 Sensor board 3 Metal film 4 Interface 6 Transport shaft 9 Refractive index matching oil 10 Coupler means 12 Cell 13 Prism 15 Sensor attachment 20 Light source optical means 23 Telecentric scanner 30 Light detecting means L Light beam

Claims (26)

[Claims] 1. A sensor unit comprising a transparent substrate having a predetermined refractive index, and a metal film disposed on one surface side of the transparent substrate, and a sensor unit provided on the opposite side of the transparent substrate from the one surface. Coupling means disposed on the front side with a refractive index matching liquid having a refractive index substantially the same as the predetermined refractive index interposed therebetween, and transmitting a light beam incident from an input portion formed in a part thereof. Incident on the interface between the transparent substrate and the metal film,
Coupler means that transmits a light beam totally reflected at the interface and exits from an output portion formed in another portion, and a portion through which the light beam transmits has a refractive index substantially equal to the predetermined refractive index; A surface plasmon sensor that causes the light beam to be incident from the input unit and detects the intensity of the light beam totally reflected at the interface and emitted from the output unit, wherein the sensor unit includes the transparent substrate and the transparent substrate. A sensor support means for supporting the gap with the coupler means so as to be always constant, wherein the gap is filled with the refractive index matching liquid, and the same light beam is incident on the interface at different locations in a predetermined direction in the interface. Incident position moving means for moving the incident position of the light beam at the input portion so as to sequentially enter in the state, or the sensor unit in a state where the interval is constant. A surface plasmon sensor further comprising at least one of a sensor unit relative moving means for moving the sensor relative to the coupler means in a predetermined direction. 2. The apparatus has both the incident position moving means and the sensor unit relative moving means, and a predetermined direction in the incident position moving means and a predetermined direction in the sensor unit relative moving means intersect each other. The surface plasmon sensor according to claim 1, wherein: 3. The surface plasmon sensor according to claim 1, wherein said incident position moving means is a telecentric scanning optical system. 4. The apparatus according to claim 1, wherein said sensor supporting means is fixed to a part of said coupler means.
3. The surface plasmon sensor according to any one of 3. to 3. above. 5. A light source optical unit for emitting a light beam and causing the light beam to enter the input unit, a detecting unit for detecting the intensity of the light beam emitted from the output unit, and the coupler unit being on a base. The sensor support means is fixed on the base, the sensor unit is movably supported by the sensor support means with respect to the coupler means, and the sensor unit relative movement means is the sensor unit. 2. The method according to claim 1, wherein
3. The surface plasmon sensor according to any one of 3. to 3. above. 6. A light source for fixing said sensor support means on a base, said sensor unit being fixedly supported by said sensor support means, emitting a light beam and causing said light beam to enter said input section. An optical unit including an optical unit, a detecting unit for detecting the intensity of the light beam emitted from the output unit, and an optical system unit including the coupler unit, the movable unit being disposed on the base with respect to the sensor unit; 2. The unit relative moving means for moving the optical system unit.
3. The surface plasmon sensor according to any one of 3. to 3. above. 7. The sensor support means is fixed on a base, the sensor unit is movably supported by the sensor support means with respect to the coupler means, and the sensor unit relative movement means is a sensor unit. Optical means for a light source for causing a light beam to enter the input unit;
An optical unit for detecting means for guiding the light beam to a detecting means for detecting the intensity of the light beam emitted from the output unit, and an optical unit including the coupler means are arranged on the base, and emit the light beam. 4. The surface plasmon sensor according to claim 1, wherein the light source and the detecting unit are detachably mounted on the base separately from the optical system unit. 8. The light source optical means for fixing the sensor support on a base, the sensor unit being fixedly supported by the sensor support, and causing a light beam to enter the input unit;
An optical system unit including a detection optical unit that guides the light beam to a detection unit that detects the intensity of the light beam emitted from the output unit, and an optical system unit including the coupler unit can be moved relative to the sensor unit on the base. The sensor unit relative moving means is for moving the optical system unit, and the light source for emitting the light beam and the detecting means are separately provided on the base from the optical system unit. The surface plasmon sensor according to any one of claims 1 to 3, wherein the surface plasmon sensor is detachably arranged. 9. The sensor support means is fixed on a base, the sensor unit is movably supported by the sensor support means with respect to the coupler means, and the sensor unit relative movement means is the sensor unit. Optical means for a light source for causing a light beam to enter the input unit;
A detecting unit for detecting the intensity of the light beam emitted from the output unit, and an optical system unit including the coupler unit are arranged on the base; and a light source for emitting the light beam is independent of the outside of the base. The surface plasmon sensor according to any one of claims 1 to 3, wherein the surface plasmon sensor is arranged so as to be arranged. 10. An optical unit for a light source, wherein the sensor support means is fixed on a base, the sensor unit is fixedly supported by the sensor support means, and a light beam is incident on the input unit.
An optical system unit including a detection unit for detecting the intensity of the light beam emitted from the output unit and the coupler unit is movably disposed on the base with respect to the sensor unit; The surface according to any one of claims 1 to 3, wherein the means moves the optical system unit, and a light source for emitting the light beam is independently disposed outside the base. Plasmon sensor. 11. The surface plasmon sensor according to claim 9, further comprising an optical fiber for guiding a light beam emitted from said light source to said light source optical means. 12. The surface plasmon sensor according to claim 11, wherein said optical fiber is a polarization-maintaining optical fiber. 13. A matching liquid supply means for supplying the refractive index matching liquid to the space, and a space leading to the space where the refractive index matching liquid can enter a position higher than the other surface of the transparent substrate. And the space is filled with the refractive index matching liquid by the matching liquid supply means.
5. The surface plasmon sensor according to any one of 4. to 4., 14. A reservoir for storing the refractive index matching liquid is formed on a side of the coupler unit facing the transparent substrate, and a waterproof wall is provided on the transparent substrate so as to surround the metal film. The surface plasmon sensor according to any one of claims 1 to 12, wherein the sensor unit is supported by the liquid reservoir so that the other surface of the transparent substrate is immersed in the refractive index matching liquid. 15. The surface plasmon sensor according to claim 1, wherein the coupler unit includes a prism, and the input unit and the output unit are formed on the prism. 16. The surface plasmon sensor according to claim 1, wherein said input part and said output part of said coupler means are formed of a diffraction grating. 17. The coupler means has a convex part on a side of the coupler means opposite to a side facing the transparent substrate, wherein the convex part is one side of the convex part and the one side. Is formed by a transparent plate, and the inside of the convex portion is filled with the refractive index matching liquid. The one side surface and the other side surface are the input portion and the output portion, respectively. 15. The method according to claim 1, wherein:
The surface plasmon sensor according to any of the above. 18. The transparent substrate of the sensor unit includes a holding substrate and a main transparent substrate disposed on the holding substrate, wherein the metal film is disposed on the main transparent substrate, and wherein the holding transparent substrate is 18. The surface plasmon sensor according to claim 1, wherein the surface plasmon sensor is disposed so as to face the coupler means via the refractive index matching liquid. 19. The surface plasmon according to claim 1, wherein a binding reaction film is provided on the metal film, and detects a specific substance that binds to and reacts with the binding reaction film. sensor. 20. A method according to claim 19, wherein a plurality of different types of binding reaction films are arranged on different portions of the metal film, and a specific substance that reacts with the binding reaction film is detected. 19. The surface plasmon sensor according to any one of 1 to 18. 21. A transparent substrate of the sensor unit, comprising: a holding substrate; and a plurality of main transparent substrates arranged at different positions on the holding substrate, wherein the metal film is formed on each of the plurality of main transparent substrates. The surface plasmon sensor according to any one of claims 1 to 17, wherein the holding transparent substrate is disposed so as to face the coupler means via the refractive index matching liquid. 22. The method according to claim 2, wherein each of the plurality of main transparent substrates has a different substrate size.
2. The surface plasmon sensor according to 1. 23. A bonding reaction film is provided on each of the metal films provided on the plurality of main transparent substrates, and a specific substance that binds to and reacts with each of the bonding reaction films is detected. The surface plasmon sensor according to any one of claims 21 to 22, wherein 24. The surface plasmon sensor according to claim 23, wherein each of the binding reaction films is a reaction film of a different type. 25. The holding transparent substrate and the main transparent substrate are brought into close contact with each other via a refractive index matching liquid having a refractive index substantially equal to the predetermined refractive index. The surface plasmon sensor according to any of the above. 26. The surface plasmon sensor according to claim 18, wherein the main transparent substrate is detachably provided on the holding transparent substrate.