JPH09257698A - Surface plasmon resonance sensor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To miniaturize a surface plasmon resonance sensor and to lower its costs. SOLUTION: A light source unit is constituted of a plurality of LED chips 79, 81 which are mounted on a board 77, of a plurality of refractive index profile-type lenses (GLIN lenses) 65a, 65b by which beams of light from the LED chips 79, 81 are condensed in respective prescribed focal positions and of a polarizing film 83 which polarizes the beams of light. Light which is radiated from the light source unit enters a light transmission medium 1, and it is incident, at a total reflection angle, on a metal thin film which is formed on the surface of the medium 1 and which is used to generate surface plsmon resonance. The light transmission medium 1 is formed in such a way that a plurality of light guiding plates 1a, 1b using, e.g. an acrylic resin plate are laminated. As the GLIN lenses 65a, 65b. A GLIN lens array in which many GLIN lenses are arranged in a row can be utilized.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a surface for measuring the refractive index of a sample such as a liquid or gas in contact with a metal thin film by utilizing the surface plasmon resonance phenomenon on a detection surface having a metal thin film of a light transmission medium. Involved in plasmon resonance sensors,
The present invention relates to improvement of an optical system for condensing light from a light source on a detection surface in a “wedge” shape.

[0002]

2. Description of the Related Art If light that travels in a medium having a high refractive index such as glass enters the interface with the outside and the incident angle is such that the light is totally reflected, the light is reflected at the interface. To totally reflect. However, if a metal thin film is in contact with the reflecting surface, light that enters at an angle within the incident angle range for total reflection causes the surface plasmon resonance phenomenon and is absorbed by the metal film. Strength decreases.
The incident angle at which such extinction is observed depends on the refractive index of the medium such as an external solution or gas in contact with the metal thin film. The surface plasmon resonance sensor is an apparatus that measures the refractive index of a sample such as a solution or gas and its variation by utilizing this phenomenon. Since the change in the refractive index of the sample reflects the change in the amount of the substance in the sample, it is possible to use the surface plasmon resonance sensor as a biosensor used in the fields of biochemistry, molecular biology, medical testing, etc. it can.

The surface plasmon resonance sensor is basically composed of
A light source, a light-transmitting medium having a high refractive index such as glass or acrylic having a detection surface in contact with the metal thin film, and a photodetector are provided. The light source unit makes light incident on the detection surface of the light transmitting medium at an incident angle satisfying the condition of total reflection, and the light detection unit receives the reflected light. In order to know the incident angle at which the extinction occurs, it is necessary to try various incident angles. A sensible way to try out these various angles of incidence simultaneously is to inject light in a "wedge" shape. That is, using a focusing lens focused on the detection surface, the light from the light source is incident on the focus on the detection surface in a "wedge" shape, and the reflected light from the focus is detected by the array type light detection. Receive with a vessel. Therefore, "wedge"
The incident angle range corresponding to the mold opening angle can be simultaneously measured.

Conventionally, a spherical lens or an aspherical lens is used to collect light from a light source in a "wedge" shape.
An optical system is composed of a single lens or a combination of a plurality of lenses. In addition, the light source is an LED or LD housed in a metal package, or a plastic-molded LE.
D lamp is used.

[0005]

In the surface plasmon resonance sensor, since the surface plasmon resonance phenomenon has temperature dependence, a large-sized device having an uneven temperature distribution in the device is not preferable. Further, in terms of application as a biosensor, it is desirable that the size be as small as possible. Taking up the optical system, I want to downsize it until the lens diameter is about 1 mm. On the other hand, the optical system is required to have extremely high-precision image forming characteristics.

However, in the above-mentioned conventional configuration,
It is difficult to reduce the size of the light source and the optical system to that extent while maintaining high accuracy. That is, with an optical system using a spherical lens or an aspherical lens, it is difficult to manufacture a highly accurate and small lens, a small lens holder that matches the lens size, and assembling the lens to the holder. . Therefore, if a small sensor is to be realized with the conventional configuration, the cost will increase.

Therefore, an object of the present invention is to provide an improvement for realizing a highly accurate and compact surface plasmon resonance sensor at low cost.

[0008]

The surface plasmon resonance sensor of the present invention is a gradient index lens (Gra) as a lens for converging light from a light source to a focal point on a detection surface.
dient Index Lens = GRIN lens) is used. The GRIN lens is generally cylindrical, and by adjusting the length thereof, a lens having desired image forming characteristics can be easily obtained, and a small lens having a diameter of about 1 mm can be easily and inexpensively obtained. Moreover, the holder is easy to manufacture because it is a simple cylinder type. As a result, a compact and high-precision optical system can be realized easily and inexpensively,
As a result, this leads to downsizing and cost reduction of the entire sensor.
When the sensor is downsized, the uneven temperature distribution in the sensor is also reduced, so that improvement in measurement accuracy can be expected.

The light source and the GLIN lens can be fixed to a common holder to form a single light source unit.
Thereby, the light source and the optical system can be integrated into a small size.

If a light source in which a LED wafer chip is mounted on a substrate or a surface mounting unit called a chip LED is used as the light source, the size can be further reduced.

It is desirable to use a GLIN lens and a light transmission medium using a light guide plate in combination. The light guide plate makes it possible to make the light transmitting medium thin and small.
By combining with a LIN lens, the size of the entire sensor can be reduced.

A small multi-channel type sensor can be manufactured by stacking a plurality of sets of structures in which a GLIN lens and a light guide plate are combined. This multi-channel type sensor can use a GLIN lens array unit in which a plurality of GLIN lenses are arranged in a line in a frame. This lens array unit can be easily obtained, and even when the thickness of the light guide plate and the lens pitch of the lens array unit do not match, a spacer is inserted between the light guide plates or the GLIN lens in the lens array unit is used. The position of each light guide plate and each GLIN lens can be easily aligned by using every other one. Therefore, the sensor can be manufactured at low cost.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of a surface plasmon resonance sensor of the present invention will be described in detail below with reference to the drawings.

FIG. 1 is an overall configuration diagram of an embodiment of a two-channel type surface plasmon resonance sensor according to the present invention.

Each of the two light guide plates 1a and 1b is, for example, an acrylic plate having a plane size of about a business card and a thickness of about 1 to several mm, and a chrome thin film deposited on both sides thereof. It is confined inside and transmits. The two light guide plates 1a and 1b are bonded to each other at their one side surfaces and laminated to form a two-channel light guide plate 1. A thin film 3 of metal such as Au is deposited on the upper end surface of the two-channel light guide plate 1 in the figure. The surface of the metal film 3 is the detection surface that contacts the sample. When used as a biosensor, a ligand layer on which a biological substance for causing a biochemical reaction with a specific substance to be detected is immobilized is formed on the detection surface. Also, this 2-channel light guide plate 1
Opposite to the left end face and the right side face in the figure,
A light source unit 5 and a light receiving sensor 7 are provided.

The light source unit 5 has two light source modules 5a and 5b, and the two light source modules 5a and 5b are selectively turned on. The light beam bundle emitted from one light source module 5a enters one light guide plate 1a, and the light beam bundle from the other light source module 5a enters the other light guide plate 1b. Each ray bundle passes through each of the light guide plates 1a and 1b and is incident on each of the focal points on the metal film 3 in a “wedge” shape at an angle of total reflection. Each ray bundle reflected by the metal film 3 is a "reverse wedge".
While passing through the light guide plates 1a and 1b, the light enters the common light receiving sensor 7. The light receiving sensor 7 is a CCD line sensor having a large number of light receiving elements arranged in a line along the direction in which the light beam spreads (that is, the vertical direction in the drawing). The output signal of the light receiving sensor 7 is input to a signal processing device (not shown).

The “wedge” -shaped light beam incident on the metal film 3 is totally reflected by the metal film 3 and enters the light receiving sensor 7. Of this bundle of rays, only the rays that enter at a specific angle determined by the refractive index of the medium on the detection surface are absorbed by causing surface plasmon resonance on the detection surface, and the amount of reflected light decreases. Therefore, a decrease in the light reception signal level is observed at the position of the light reception sensor 7 corresponding to the incident angle. From the position where this level decrease is observed, the refractive index of the medium on the detection surface is known, and as a result, the substance to be measured in the sample can be detected.

The two-channel sensor can be used as follows. For example, a ligand layer having an active biological substance immobilized thereon is formed on the first channel side portion of the metal film 3, and a non-active biological substance immobilized ligand layer is formed on the second channel side portion thereof. To do. Then, the first channel is used for measurement of the target substance, the second channel is used as a reference standard, and temperature compensation for the measurement value from the first channel is performed using the reference standard value from the second channel. As a result, in the surface plasmon resonance sensor having a high temperature dependence, a highly accurate temperature-compensated measurement result can be obtained. Further, for example, by using the two channels for measuring two different target substances, it is possible to simultaneously inspect a plurality of substances or perform a comparative inspection.

By stacking an arbitrary number of light guide plates and arranging the same number of light source modules in the same manner as this embodiment, a sensor having an arbitrary number of channels can be easily manufactured. Of course, a single channel sensor can be easily manufactured.

FIG. 2 is a sectional view showing an example of a single-channel light source unit that can be used in the embodiment of the present invention.
By arranging two light source units, the light source unit 5 for two channels shown in FIG. 1 can be constructed.

As shown in FIG. 2, a cylindrical gradient index lens (GLIN) is provided in one cylindrical lens holder 11.
The lens) 17 is fixedly held. A circuit board 15 having an LED wafer chip (hereinafter referred to as an LED chip) 13 as a light source mounted thereon is adhered to the base end surface of the lens holder 11, and a polarizing film 19 is adhered to the tip end surface of the lens holder 11. There is. GLIN lens 17
Is a type that forms an erecting equal-magnification image, for example.
The LED chip 13 is arranged almost on the central axis of the GLIN lens 17, and its image is formed by the GLIN lens 17 at a position of a focal point f ahead by a predetermined distance from the light source unit.

The circuit board 15 is a board such as glass epoxy, ceramic, paper phenol, etc. used for ordinary electronic equipment. The LED chip 13 has a size of about 300 μm and is mounted on the circuit board 15 by die bonding, wire bonding, or the like. AlGaAs double hetero type L
ED is preferred, but other types may be used. Desirably, the surface of the LED chip 13 is coated with a precoating agent made of silicone resin for increasing the light extraction efficiency. Instead of the LED chip 13 mounted on the substrate 15, a surface mounting unit called a chip LED can be used. The chip LED has an LED chip mounted on a base having external connection terminals, and there is a chip LED having a size of about 1 mm. Also, instead of LED, LD
Other light emitting elements such as (semiconductor laser) that emit light of a single wavelength can also be used.

Since the polarizing film 19 is for producing polarized light for exciting surface plasmons, if the position is between the LED chip 13 and the metal film 3 (see FIG. 1), it is shown in the drawing. It is not limited to the position. The lens holder 11 is made of, for example, a black resin or a black anodized aluminum cylindrical tube, but its material is not limited to black as long as it is a material that hardly reflects the light of the light source.

The GLIN lens 17 can be easily manufactured in a small size having a diameter of about 1 mm. Since the GLIN lens 17 has a cylindrical shape, the lens holder 11 can also have a simple cylindrical shape, and the lens holder 11 can be easily manufactured.
In addition to such geometrical simplicity, since the GLIN lens 17 can be fixed to the lens holder 11 with an adhesive,
It can be easily incorporated into the lens holder 11. Furthermore, LED
The chip 13 has a small size of about 300 μm, and the substrate 15
It is easy to mount on the surface, and it is also easy to attach the substrate 5 to the end portion of the lens holder 11. For these reasons, a compact and highly accurate light source unit can be easily manufactured at low cost. 1 even when using a chip LED
Since it is as small as about mm, a small light source unit can be easily obtained.

FIG. 3 is a sectional view showing an example of another single-channel light source unit that can be used in the embodiment of the present invention. This light source unit is a single GLIN shown in FIG.
Instead of lens 17, GLIN lens 2 for collimation
1 and the GLIN lens 23 for condensing. Since the image forming characteristics of the two GLIN lenses 21 and 23 can be selected separately, the options of the image forming characteristics of the light source unit are wider than those in FIG.

FIG. 4 is a block diagram of two usable in the embodiment of the present invention.
It is sectional drawing which shows the example of the light source unit for channels. The lens holder 31 has two parallel cylindrical cavities 51 and 53, in which two GLIN lenses 33 and 35 having the same characteristics are fitted. A circuit board 37 is adhered to the base end surface of the lens holder 31, and two LED chips 39 and 41 are mounted on the circuit board 37 at positions corresponding to the central axes of the two GLIN lenses 33 and 35, respectively. ing. A polarizing film 43 is adhered to the tip surface of the lens holder 31. In this way, the two light source modules 55 and 57 are integrated into one unit.

The two-channel light source unit is arranged as shown in FIG. 5 with respect to the two light guide plates 1a and 1b shown in FIG. That is, the two light source modules 55 and 57
Are arranged so that they are respectively located at the centers of the widths of the two light guide plates 1a and 1b.

A light source unit for three or more channels can be manufactured with the same structure.

FIG. 6 is a perspective view showing a GLIN lens array 67 suitable for making a multi-channel light source unit. A large number of GLIN lenses 65 are precisely arranged in a row at equal pitches between the two frame plates 61 and 63. The gap between the lenses 65 is filled with black silicone resin for removing flare light. The silicone resin has a rubber shape so as not to give stress to the lens 65. The frame plates 61 and 63 include a lens 65.
It is a black laminated board of glass cloth base epoxy resin having almost the same characteristics as the thermal expansion of. With this configuration, the thermal strain on the lens 65 is reduced, and the GLIN lens array 67 is provided.
The overall strength increases.

FIG. 7 is a sectional view showing a structural example of a light source unit for two channels using this GLIN lens array 67. In this example, the thickness of each of the light guide plates 1 a and 1 b is twice the diameter of the GLIN lens 65, and therefore, every other GLI in the GLIN lens array 67 is included.
Only the N lenses 65a and 65b are used as lenses.

As shown in FIG. 7, two cylindrical cavities 7 are provided.
The circuit board 77 is adhered to the base end surface of the holder 71 having the three and 75, and the two LED chips 7 are mounted on the circuit board 77.
9, 81 are mounted, and the LED chips 79, 81 are arranged at positions corresponding to the central axes of the cavities 73, 75. On the tip surface of the holder 71, the GLIN lens array 6
7 is fixed and the two lenses 65 in this array 67 are fixed.
a and 65b are arranged with their central axes aligned with those of the cavities 73 and 75. GLIN lens array 67
3 unused lenses 65c, 65d, 65e
A spacer 81 is adhered to the tip surface of the so as to shield light. The spacer 81 may be arranged on the light incident side of the GLIN lens. A polarizing film 83 is adhered to the tip surface of the spacer 81.

The light from each LED chip 79, 81 is incident on every other GLIN lens 65a, 65b, is polarized by the polarizing film 83, and is incident on the corresponding light guide plate 1a, 1b.

The diameter of the GRIN lens 65 and the light guide plate 1
When the thicknesses a and 1b are the same, the continuous GLIN lens in the GLIN lens array 67 can be used as a lens by reducing the thickness of the partition wall of the holder 71. When the diameter of the lens and the thickness of the light guide plate are different, each light source module and each light guide plate 1a, 1b can be aligned by inserting a spacer having an appropriate width between the light guide plates 1a, 1b. it can.

[0034]

As described above, according to the present invention,
The surface plasmon resonance sensor can be easily miniaturized.

[Brief description of drawings]

FIG. 1 is a perspective view showing an embodiment of a two-channel type surface plasmon resonance sensor.

FIG. 2 is a sectional view showing a configuration example of a light source unit that can be used in an embodiment of the present invention.

FIG. 3 is a sectional view showing a configuration example of another light source unit.

FIG. 4 is a sectional view showing a configuration example of a light source unit for two channels.

5 is a front view showing the positional relationship between each light source module and each light guide plate of the light source unit shown in FIG.

FIG. 6 is a perspective view showing a GLIN lens array.

FIG. 7 is a sectional view showing a light source unit for two channels using a GLIN lens array.

[Explanation of symbols]

1 Light guide plate 3 Metal film 5 Light source unit 7 Light receiving sensor 11, 31 Lens holder 13, 39, 41, 79, 81 LED chip 15, 37, 77 Circuit board 17, 21, 23, 33, 35, 65 Refractive index distribution type Lens (GRIN lens) 19, 43, 83 Polarizing film

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Taiji Nagata 2-1-1 Nakajima, Kokurakita-ku, Kitakyushu City, Fukuoka Prefecture Totoki Kikai Co., Ltd. (72) Inventor Katsumi Yoneda Horo-cho, Tenpaku-ku, Nagoya 2318 Japan Laser Electronics Co., Ltd. (72) Inventor Haruo Tajima 2318 Horo-cho, Tenpaku-ku, Nagoya-shi, Aichi Japan Laser Electronics Co., Ltd.

Claims (8)

[Claims] 1. A surface plasmon resonance sensor comprising: a light source; and a light transmissive medium having a detection surface for receiving light from the light source to cause surface plasmon resonance. The surface plasmon resonance sensor is disposed between the light source and the detection surface. A surface plasmon resonance sensor comprising a gradient index lens for collecting light from the light source onto the detection surface. 2. The surface plasmon resonance sensor according to claim 1, further comprising a light source unit in which the light source and the gradient index lens are fixed to a common holder. Sensor. 3. The surface plasmon resonance sensor according to claim 1, wherein the light transmission medium is a light guide plate for guiding the light passing through the gradient index lens to the detection medium. Surface plasmon resonance sensor. 4. The surface plasmon resonance sensor according to claim 1, wherein the surface plasmon resonance sensor of a multi-channel type is provided with a plurality of sets in which the gradient index lens and the light transmitting medium are combined. 5. The surface plasmon resonance sensor according to claim 4, wherein the light transmission medium in each of the plurality of sets guides light passing through the gradient index lens to the detection medium. A multi-channel surface plasmon resonance sensor, which is an optical plate, wherein the plurality of sets are arranged in parallel so that the plurality of light guide plates are stacked. 6. The surface plasmon resonance sensor according to claim 5, comprising a lens array in which a plurality of the gradient index lenses are arranged in a line in a common frame. Type surface plasmon resonance sensor. 7. The surface plasmon resonance sensor according to claim 1, wherein the light source is a wafer chip of an LED mounted on a circuit board. 8. The surface plasmon resonance sensor according to claim 1, wherein the light source is a chip LED.