JP2007155477A - Surface plasmon resonance sensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To always make constant an outgoing end of a light source means and the relative angle of a prism to a light receiving means with an inexpensive constitution without using an angle adjustment mechanism. <P>SOLUTION: The surface plasmon resonance sensor 1 comprises a plate-like sensor chip 20 whose one end surface integrally has a prism 10 forming a metal thin film 2 on its surface 10a. The sensor chip 20 has a through hole 24 reaching the surface 10a of the prism 10. The surface plasmon resonance sensor 1 also comprises a prism fixing stand 51 for fixing the prism 10 by closely adhering it on a fixed surface 10b, and a pressing member 52 capable of being inserted into or removed from the through hole 24. The prism 10 is pressed and arranged on the prism fixing stand 51 by the pressing member 52, and the relative angles among the prism 10, an outgoing end 30a of an optical fiber 30, and a light receiving sensor 40 are made constant. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a surface plasmon resonance sensor that irradiates a specimen with light emitted from a light source and acquires information relating to the specimen from reflected light from the specimen or transmitted light that has passed through the specimen.

2. Description of the Related Art Conventionally, a surface plasmon resonance sensor (hereinafter referred to as an SPR sensor), which is one of optical sensors, uses a surface plasmon resonance (hereinafter referred to as SPR as necessary) to permit the dielectric constant of a substance on a metal thin film. In recent years, it has been frequently used as a material sensor because of its high sensitivity and its ability to observe on the spot. An example of this SPR sensor is disclosed in Patent Document 1.
In Patent Document 1, when P-polarized light having a certain wavelength propagating in a dielectric is reflected by a surface coated with a metal such as gold or silver, the density of free electrons on the surface of the metal is reflected at a specific angle (resonance angle). It is a sensor that applies the fact that the intensity of emitted light is reduced because it is absorbed in resonance with a wave (plasmon). As is well known, this resonance angle depends on the refractive index of the substance (analyte) on the metal surface (surface opposite to the dielectric).

  As is clear from this, the accuracy of measurement of the angle of incidence on the metal surface is the accuracy of the sensor. Transparent dielectrics used in actual devices are made of glass or acrylic, and their refractive index is about 1.4 to 1.5. For this reason, when air enters between the dielectric and the measurement light emitting part, or between the dielectric and the measurement light receiving part, that is, when the dielectric, the emission part, and the light receiving part are not integrated, the reflected light on the metal surface is In order to take it out of the body, the dielectric needs to have a triangular cross section or a semicircular cross section as in Patent Document 1. Since the SPR sensor can measure the concentration of the specimen even if light does not pass through the specimen, it can be applied to the concentration measurement of a substance that does not transmit light such as blood.

The measurement using a commonly used SPR sensor makes it possible to measure a change in a specimen in a minute region by collecting light using a lens or the like. For example, Patent Document 2 discloses an SPR sensor that processes a tip portion of a light guide core of an optical fiber.
Patent Document 2 is a sensor head in which the diameter of a light guide core of about several μm is sharpened with respect to the light guide direction. By using the emission end face of such an optical fiber as a point light source, a desired minute region can be measured. However, it is difficult to manufacture because the angle must be processed with high accuracy in the region of several μm in diameter.
Furthermore, since the outgoing angle of the outgoing light from the optical fiber is limited by the refractive index distribution of the light guide core, the angular accuracy of the prism position and the outgoing end is important.

Therefore, in the conventional SPR devices, this angle has been kept constant by using a device in which a dielectric (prism), a light emitting portion, a light receiving portion are integrated, or a device having an angle adjusting mechanism. However, when it is used for a disposable application such as a blood sensor, a combination of a dielectric, a light emitting portion, and a light receiving portion has a drawback of high cost. As what is used for a disposable use, there exist some which are indicated by patent documents 3, for example.
Patent Document 3 proposes a prism-attached chip in which a prism is fixed to the lower surface of a measurement chip. After use, each chip with a prism can be replaced with a new one.
Japanese Patent No. 2758904 JP 2001-165852 A JP 2000-97848 A

  However, in Patent Document 3, it is necessary to adjust the angle between the prism and the end face of the optical fiber every time the tip with the prism is replaced. This angle adjustment uses an angle adjustment mechanism, and the angle adjustment mechanism itself is expensive, which causes a problem of increasing the cost of the SPR sensor.

  The present invention has been made in view of such circumstances, and the relative angle of the prism with respect to the emission end of the light source means and the light receiving means is always constant with an inexpensive configuration without using an angle adjustment mechanism. An object of the present invention is to provide a surface plasmon resonance sensor.

  In order to achieve the above object, a surface plasmon resonance sensor according to the present invention includes a flat sensor chip integrally provided with a prism having a metal thin film formed on the surface thereof bonded or non-bonded to one end surface side. A surface plasmon resonance sensor that irradiates the metal thin film with incident light from a light source means through the prism at a constant angle, and detects light reflected by the metal thin film with a light receiving means, wherein the sensor chip includes the prism A through hole reaching the surface is formed, a prism fixing base is provided for fixing the prism in close contact with a fixing surface opposite to the surface of the prism, and a pressing member is provided to allow insertion and extraction within the through hole. The prism is pressed against the prism fixing base by the pressing member, and the prism, the emission end of the light source means, and the light receiving means The relative angle is always characterized in that it is configured to be constant.

  In the surface plasmon resonance sensor according to the present invention, it is preferable that the angle formed between the normal line of the incident surface of the prism and the incident light is larger than the emission angle from the emission end of the light source means.

  In the surface plasmon resonance sensor according to the present invention, the light source means is preferably an optical fiber.

  In the surface plasmon resonance sensor according to the present invention, the light source means is preferably a polarization maintaining optical fiber.

  In the surface plasmon resonance sensor according to the present invention, it is preferable that a surface of the prism is parallel to a prism reference surface of the prism fixing base that closely contacts the prism.

  In the surface plasmon resonance sensor according to the present invention, it is preferable that a sample flow path that flows so that the sample directly contacts the metal thin film is formed in the sensor chip.

  The surface plasmon resonance sensor according to the present invention is preferably provided with a side pressing member that presses the side of the prism to adjust the horizontal position.

  In the surface plasmon resonance sensor according to the present invention, it is preferable that a sensitizer or a reagent for adjusting the angle is applied to the surface of the metal thin film.

According to the surface plasmon resonance sensor of the present invention, the prism is brought into close contact with the prism fixing base with a simple structure in which the prism integrally provided on the sensor chip is pressed by the pressing member, and is securely fixed with high precision. It can be arranged by position and angle. Thereby, the relative angle of the prism with respect to the emission end of the light source means and the light receiving means can always be kept constant, and repeated accurate measurement can be performed.
And since it is the structure which does not require an expensive angle adjustment mechanism like the past, the cost of a surface plasmon resonance sensor can be reduced.

Hereinafter, a first embodiment of a surface plasmon resonance sensor according to the present invention will be described with reference to the drawings.
1A and 1B are diagrams showing a surface plasmon resonance sensor according to a first embodiment of the present invention, in which FIG. 1A is an elevational sectional view, FIG. 1B is a plan view thereof, and FIGS. b) is a diagram showing the relationship between the angle formed by the prism and the incident light.

As shown in FIGS. 1A and 1B, a surface plasmon resonance sensor 1 (hereinafter sometimes referred to as an SPR sensor 1) according to the first embodiment contacts a test sample (specimen). The prism 10 having the surface 10a coated with the surface plasmon excitation metal thin film 2 to be applied, the flat sensor chip 20 integrally provided with the prism 10 on one end surface side, and the output light from the light source 31 is incident to the prism 10 An optical fiber 30 (light source means) that outputs light irradiated to the metal thin film 2, a light receiving sensor 40 (light receiving means) that detects a change in the intensity of the light reflected by the metal thin film 2, and the prism 10 are arranged at predetermined positions. And a prism holding mechanism 50 for holding.
The prism holding mechanism 50 includes a prism fixing base 51 that fixes the prism 10 in close contact with the fixing surface 10b, and a pressing member 52 that presses the prism 10 toward the prism fixing base 51.
In addition, the surface plasmon resonance sensor 1 is provided with a chip support 60 for mounting or fixing the sensor chip 20 at a predetermined position.
Hereinafter, the sensor chip 20 on which the prism 10 is mounted as necessary is also referred to as a prism-equipped chip 20.

  The metal thin film 2 forms a reflective surface in which the surface 10a of the prism 10 is coated with a material such as gold or silver. Note that the surface of the metal thin film 2 can be preliminarily coated with a sensitizer for increasing the change in refractive index and a reagent for adjusting the refraction angle to be within the measurement range. is there. A reagent (specimen) that binds to a specific protein, sugar, or the like is supplied to the metal thin film 2 through a sample flow path 25 (described later) of the sensor chip 20. The sample to be tested for surface plasmon resonance measurement can be easily replaced by replacing the prism-equipped tip 20.

  As shown in FIGS. 1A and 1B, the prism 10 has a surface 10a and a fixed surface 10b which are parallel to each other, and the incident surface 10c and the exit surface 10d are symmetric with respect to a cross section in a predetermined angle. It is formed in a trapezoidal shape. That is, the entrance surface 10c and the exit surface 10d are at the same angle with respect to the surface 10a.

  As the light source 31, it is not necessary to use an expensive and large-scale device such as a gas laser or a solid-state laser, and a small and low-cost device can be used. The light source 31 that can be used may be either a coherent light source such as a semiconductor laser or an incoherent light source such as a light emitting diode (LED) or a lamp.

  As the optical fiber 30, a known polarization maintaining optical fiber for a light source is adopted (hereinafter, the optical fiber 30 is also referred to as a polarization maintaining optical fiber 30), and P-polarized light is emitted from the emission end 30a. It is. The polarization maintaining optical fiber 30 is a so-called PANDA type optical fiber (PANDA: Polarization-maintaining AND Absorption reducing). The polarization maintaining optical fiber 30 can function as a polarization filter that converts light in a polarization state other than linearly polarized light out of incident light from the light source 31 into linearly polarized light.

  As the light receiving sensor 40, for example, a sensor using a light receiving element having a single pixel is employed. The light receiving sensor 40 is installed so that its position and orientation with respect to the prism 10 (more precisely, the metal thin film 2 formed on the prism 10) are constant.

Here, the installation position of the prism 10 and the optical fiber 30 in the SPR sensor 1 will be described.
As shown in FIG. 1A, the optical fiber 30 is configured so that light emitted from an emission end 30 a (an end on the prism 10 side, an end opposite to the light source 31) is emitted at a certain angle with respect to the prism 10. It arrange | positions so that it can radiate | emit. The position of the optical fiber 30 with respect to the metal thin film 2 is always constant and fixed.
The installation position of the prism 10 and the optical fiber 30 (exactly the emission end 30a) is the incident angle of incident light on the reflecting surface forming the metal thin film 2 (θ shown in FIG. 2) at the relative angle between the prisms 10 and 30. Is set to be the resonance angle of water (for example, about 65 °).
The spread of the emitted light by the optical fiber 30 has an angular dimension of about ± 5 °. This divergence angle corresponds to an incident angle of about ± 3 ° with respect to a reflective surface coated with a metal thin film when it is incident on an equilateral triangular prism made of an acrylic material having a refractive index of about 1.5, for example. That is, since the angle can be detected if the surface plasmon resonance peak is within the measurement center angle ± 3 °, the SPR sensor 1 can measure the surface plasmon resonance peak with a very simple structure having no movable part.

As shown in FIGS. 1A and 1B, the sensor chip 20 is composed of two thin plates, and an upper chip 21 (on the side opposite to the side where the prism 10 is arranged) and a lower chip 22 (on the prism side). It is formed by bonding.
The sensor chip 20 is formed with a fitting portion 23 to be fitted so as to accommodate the upper portion (surface 10a) of the prism 10, and the fitting portion 23 is fitted in a state where the upper portion of the prism 10 is not bonded or separated. It is the structure which was made to provide integrally.

  The chip 20 with prism is formed with a plurality of through holes 24 (eight in this embodiment) that reach the surface 10a of the prism 10 from the upper surface 20a and penetrate in the thickness direction of the sensor chip 20. . The position of the through hole 24 in the sensor chip 20 is arranged by shifting the position of the metal thin film 2 formed on the prism 10 in a plan view shown in FIG. 1B, and the surface 10 a of the prism 10 is directly below the through hole 24. Become.

  In addition, a groove-like specimen flow path 25 is formed on the mating surface 21a of the upper chip 21 so that a specimen (specimen) such as a drug directly contacts the metal thin film 2 of the prism 10. The sample channel 25 is connected to a sample inlet portion 26 provided at a predetermined position on the upper surface 20 a of the sensor chip 20. Then, the sample flows into the sensor chip 20 from the sample inlet portion 26.

  The prism fixing base 51 is provided such that the surface 10a of the prism 10 and the fixing surface 10b are parallel to the prism reference surface 51a that forms the upper surface. The prism fixing base 51 is fixed at a position where the prism 10 can be disposed so as to have a certain relative angle with respect to the optical fiber 30 (the emitting end 30a) and the light receiving sensor 40.

Next, the pressing member 52 of the prism holding mechanism 50 will be described.
As shown in FIGS. 1A and 1B, the pressing member 52 is fixed to a cylindrical cylindrical member 52a having a diameter smaller than the diameter of the through-hole 24, and a tip (one end) of the cylindrical member 52a on the prism 10 side. The pressing portion 52b. The other end side of the pressing member 52 is attached to an elevator (not shown), for example, and is provided so as to be inserted and removed in a direction in which the surface 10 a of the prism 10 is pressed in the through hole 24.

In the holding member 52 configured as described above, the prism 10 is disposed above the prism reference surface 51 a of the prism fixing base 51 in a state where the prism-equipped chip 20 is placed or fixed at a predetermined position of the chip support base 60. The Then, the pressing member 52 is inserted into the through hole 24, and the surface 10a of the prism 10 is pressed by the pressing portion 52b. Then, the fixed surface 10b of the prism 10 and the prism reference surface 51a of the prism fixing base 51 are in close contact with each other. Since the prism 10 is formed with optical accuracy, the surface 10 a of the prism 10 (that is, the measurement surface having the metal thin film 2) can be parallel to the prism reference surface 51 a of the prism fixing base 51.
Note that the pressing by the pressing member 52 maintains the pressed state so that the position of the prism 10 does not move during the inspection.
Thus, by providing the prism holding mechanism 50, the relative angle between the prism 10, the emission end 30a of the optical fiber 30, and the light receiving sensor 40 can be made constant at all times.

Further, the pressing member 52 can independently press only the prism 10 regardless of the sensor chip 20. For this reason, for example, even when there is a manufacturing error in the dimensions of the sensor chip 20, the prism 10 can always be arranged at a predetermined position and angle with respect to the installation position of the optical fiber 30 and the light receiving sensor 40.
That is, the fixing surface 11b of the prism 11 only needs to be held in close contact with the prism reference surface 51a of the prism fixing base 51. At this time, the sensor chip 20 does not need to perform angle adjustment with high accuracy. Further, it is not necessary to finish the sensor chip 20 with high accuracy, and the processing cost of the sensor chip 20 can be reduced.

As shown in FIG. 1B, it is preferable that the pressing members 52 are provided in the same number as the through holes 24 and pressed against the surface 10 a of the prism 10 at a plurality of locations.
Further, the prism-equipped chip 20 is stored in, for example, a case (not shown), and when the prism-equipped chip 20 is set in the SPR sensor 1, the prism 10 is fixed so that the fixed surface 10b of the prism 10 is exposed from the case. It is good also as a structure arrange | positioned closely to the fixed stand 51. FIG.

Next, the angle formed between the prism 10 and the incident light will be specifically described with reference to FIG.
As shown in FIG. 2A, the incident angle θ of the measurement light on the metal thin film 2 is θ ₊ and θ ₋ with respect to the angle θ _{p of the} prism side surface and the refractive index of the prism 10 as n. Like
θ _- the side is,
θ = θ _p −sin ⁻¹ (sin θ ₋ / n) (1)
On the θ ₊ side,
θ = θ _p + sin ⁻¹ (sin θ ₊ / n) (2)
It becomes.
Therefore, as shown in FIG. 2 (b), the output angle from the optical fiber 30, if a ± theta _[delta], the normal line of the optical fiber 30 and the prism 10 are the angle and theta _i,
θ _i > θ _δ (3)
In this case, it is possible to calculate θ only by the above-described equation (2),
θ _i > −θ _δ (4)
In this case, it is possible to calculate θ using only the above-described equation (1).
Thus, it is preferable that the absolute value of θ _i is larger than θ _δ . If -θ _δ <θ _i <θ _δ , it is necessary to switch the equations (1) and (2) when θ _i = 0, which is not preferable because the equations become complicated.

In the first embodiment, the prism 10 (see FIG. 1A) has a trapezoidal cross section, but instead, the second prism 11 having a substantially square cross section as shown in FIG. It is also possible to apply to. The second prism 11 has a shape in which the entrance surface 11 c and the exit surface 11 d are substantially orthogonal to the prism reference surface 51 a of the prism fixing base 51.
In the second prism 11, the incident angle applied to the metal thin film 2 is different from that in the trapezoidal prism 10, so that the second prism 11, the optical fiber 30 (emission end 30 a), and the light receiving sensor 40 are connected to each other. Each is arranged so as to have a predetermined relative angle corresponding to the second prism 11.

As described above, in the surface plasmon resonance sensor 1 according to the first embodiment, the prism 10 is closely attached to the prism fixing base 51 by a simple structure in which the prism 10 integrally provided on the sensor chip 20 is pressed by the pressing member 52. Thus, it can be reliably fixed with high precision and arranged at a predetermined position and angle. Thereby, the relative angle of the prism 10 with respect to the emitting end 30a of the optical fiber 30 and the light receiving sensor 40 can always be kept constant, and repeated accurate measurement can be performed.
And since it is the structure which does not require an expensive angle adjustment mechanism like the past, the cost of the surface plasmon resonance sensor 1 can be reduced.

Next, the second and third embodiments of the surface plasmon resonance sensor of the present invention will be described with reference to FIGS. 4 and 5, and the same or similar members and parts as those of the first embodiment described above are used. The description is omitted by using the same reference numerals, and a configuration different from the first embodiment will be described.
4 (a) and 4 (b) are elevational sectional views showing a surface plasmon resonance sensor according to a second embodiment of the present invention.
As shown in FIG. 4A, the surface plasmon resonance sensor 1 according to the second embodiment employs a prism 10 having a substantially trapezoidal cross-sectional view similar to that of the first embodiment. The prism-attached chip 20 is integrated with the sensor chip 20 by adhering the upper peripheral edge 10 e of the prism 10 to the fitting part 23 of the sensor chip 20.
In this structure, when the prism 10 is pressed against the prism fixing base 51 by the pressing member 52 and held, the sensor chip 20 is inclined according to the prism 10. For this reason, the sensor chip 20 is not necessarily in a fixed state in close contact with the chip support 60 (see FIG. 1A). However, since the prism 10 itself is held at a predetermined position, this SPR sensor is used. The measurement by 1 is not affected. For this reason, the chip support is omitted in FIG.
As shown in FIG. 4B, in the second embodiment, a second prism 11 having a substantially quadrangular sectional shape may be employed instead of the trapezoidal prism 10.

Next, FIG. 5 is an elevational sectional view showing a surface plasmon resonance sensor according to a third embodiment of the present invention.
As shown in FIG. 5, the surface plasmon resonance sensor 1 according to the third embodiment holds down the surfaces 10a and 11a (see FIGS. 1 and 4) of the prisms 10 and 11 of the first and second embodiments. In addition to this, the side surface pressing member 53 for pressing the side surface 10f (including the incident surface 10c and the output surface 10d) of the prism 10 is provided.
According to this, the side surface 10f of the prism 10 is pressed by the side surface pressing member 53, so that the prism 10 is approximately horizontal (the direction substantially orthogonal to the pressing direction of the pressing member 52 that presses the surface 10a of the prism 10). The position can be moved.

Although the first to third embodiments of the surface plasmon resonance sensor according to the present invention have been described above, the present invention is not limited to the first to third embodiments described above, and departs from the spirit thereof. It is possible to change appropriately within the range not to be.
For example, in the first to third embodiments, the optical fiber 30 is provided in the light source means for emitting the incident light to be irradiated onto the metal thin film 2, but the present invention is not limited to this, and the conventional collection is performed. A light source using a light lens may be applied.
In the first embodiment, eight through-holes 24 are formed. However, the number and arrangement positions of the through-holes 24 may be set as appropriate according to the shape and dimensions of the prism.
Further, in the first to third embodiments, the prisms 10 and 11 are fitted and integrated with the sensor chip 20, but the structure is not limited to this fitting. In short, in a state where the prisms 10 and 11 and the sensor chip 20 are integrated, the pressing member 52 is inserted into the through hole 24 formed in the sensor chip 20 to press the surface 10a of the prism 10. It's fine.

It is a figure which shows the surface plasmon resonance sensor by 1st embodiment of this invention, Comprising: (a) is the standing sectional view, (b) is the top view. (A), (b) is a figure which shows the relationship between the angle which a prism and incident light make. It is a figure which shows the relationship of the direction of the incident light in a prism. It is an elevation sectional view showing a surface plasmon resonance sensor according to a modification of the first embodiment. (A), (b) is an elevational sectional view showing a surface plasmon resonance sensor according to a second embodiment of the present invention. It is a sectional elevation showing a surface plasmon resonance sensor according to a third embodiment of the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Surface plasmon resonance sensor, 2 ... Metal thin film, 10 ... Prism, 10a ... Surface, 10b ... Fixed surface, 20 ... Sensor chip, 23 ... Fitting part, 24 ... Through-hole, 25 ... Sample flow path, 30 ... Light Fiber (light source means), 30a ... emitting end, 31 ... light source, 40 ... light receiving sensor (light receiving means), 51 ... prism fixing base, 51a ... prism reference surface, 52 ... pressing member, 53 ... side pressing member, 60 ... chip Support stand

Claims (8)

A flat sensor chip is provided with a prism having a metal thin film formed on its surface, bonded or not bonded to one end surface, and incident light is irradiated from the light source means to the metal thin film through the prism at a certain angle. A surface plasmon resonance sensor in which light reflected by the metal thin film is detected by a light receiving means,
A through hole reaching the surface of the prism is formed in the sensor chip,
A prism fixing base for fixing the prism in close contact with a fixing surface opposite to the surface of the prism;
A pressing member is provided that can be inserted and removed from the through hole,
The prism is configured such that the relative angle between the prism, the emitting end of the light source means, and the light receiving means is always constant by pressing the prism against the prism fixing base. A surface plasmon resonance sensor.   2. The surface plasmon resonance sensor according to claim 1, wherein an angle formed between a normal line of the incident surface of the prism and the incident light is larger than an emission angle from an emission end of the light source means.   3. The surface plasmon resonance sensor according to claim 1, wherein the light source means is an optical fiber.   3. The surface plasmon resonance sensor according to claim 1, wherein the light source means is a polarization maintaining optical fiber.   5. The surface plasmon resonance sensor according to claim 1, wherein a surface of the prism is parallel to a prism reference surface of the prism fixing base that closely contacts the prism.   The surface plasmon resonance sensor according to any one of claims 1 to 5, wherein a sample flow path is formed in the sensor chip so that the sample directly contacts the metal thin film.   The surface plasmon resonance sensor according to claim 1, further comprising a side pressing member that presses a side surface of the prism to adjust a horizontal position. 8. The surface plasmon resonance sensor according to claim 1, wherein a sensitizer or an angle adjusting reagent is applied to the surface of the metal thin film.

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