JP2000065729A - Sensor chip for surface plasmon resonance angle detection device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sensor chip of SPR device capable of efficiently detecting the resonance angle of many kinds of sample constituents. SOLUTION: The surface plasmon resonance angle detection device applies light with a required angle width to the incidence side of a prism 5 that adheres to a sensor chip 7 where a sample solution is sucked and detects a resonance angle where the absorbance to the sample solution can be maximized according to the intensity of reflection light from the sensor chip 7 for specifying a sample constituent. A glass substrate 13 where a metal thin film is formed on an upper surface at each cell side is mounted to the lower surface of a cell plate 15 where a number of cells 15a whose lower surface is open are provided with a required gap so that the opening of each cell can be closed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sensor chip of a surface plasmon resonance angle detecting device (hereinafter, referred to as an SPR device) for specifying a sample component by a resonance angle at which the absorbance with respect to a sample solution is maximized.

[0002]

The sensor chip of the SPR apparatus has a structure in which a metal thin film, for example, at least one of a gold thin film and a silver thin film is formed on the surface of a glass substrate, and a prism is formed on the glass substrate on the opposite side of the metal thin film. It is configured to be in close contact. Then, after the sample solution as an object to be detected is fixed on a metal thin film on a glass substrate to which an antibody or a reagent for detecting a specific substance in the sample solution is attached in advance, light from a light source is applied to the incident side of the prism. And the resonance angle at which the intensity of the reflected light from the metal thin film is minimized to identify the sample components.However, in order to detect various types of sample solution components, A work of dispensing and fixing the sample solution on the metal thin film and a work of washing the sample solution fixed on the metal thin film after detection are required.

[0003] Further, since antibodies and reagents for detecting a specific substance contained in the sample components are different depending on the sample components, it is necessary to replace the glass substrate on which the corresponding antibodies and reagents are attached according to the sample components. In this case, each time, the prism and the glass substrate must be brought into close contact with each other, and the replacement work is troublesome.

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned conventional disadvantages, and an object of the present invention is to provide an SPR apparatus capable of efficiently detecting resonance angles of various kinds of sample components. In providing a sensor chip.

[0005]

Therefore, according to the present invention, a light having a required angle width is irradiated on the incident side of a prism which is in close contact with a sensor chip to which a sample solution is adsorbed, and the intensity of reflected light from the sensor chip is adjusted. In a surface plasmon resonance angle detection device that detects a resonance angle at which the absorbance of a sample solution becomes maximum and specifies a sample component, a cell plate in which a large number of cells each having a sensor chip opened on the lower surface is provided at required intervals. And a glass substrate which is attached to the lower surface of the cell plate so as to close the opening of each cell, and has a thin metal film formed on the upper surface of each cell.

Then, different types of sample solutions dispensed into each cell are selectively brought into close contact with a prism on the lower surface of the glass substrate corresponding to each cell, and the respective resonance angles are continuously detected.

[0007]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will be described below with reference to the drawings. FIG. 1 is a partially sectional explanatory view showing the outline of an SPR device. FIG. 2 is an exploded perspective view of a partial cross section of the sensor chip.

First, the outline of the SPR device 1 will be described.
The prism mounting block 3 of the SPR device 1 has a half-split cylindrical prism 5 mounted so that the upper surface thereof is substantially flush with the upper surface of the prism mounting block 3. The prism 5 has a size that substantially matches the size of a single cell 7a in the sensor chip 7 for multiple specimens described later.

The light entrance path 3a and the light exit path 3b are formed in the block 3 corresponding to the light entrance side and the light exit side of the prism 5. The opening width of each of the light entrance passage 3a and the light exit passage 3b is set such that the incident angle and the exit angle of the light to the prism 5 are about 35 to 80 degrees and 100 to 145 degrees.

A light source 9 is arranged on the light incident passage 3a side, and a light receiving device 11 is arranged on the light exit passage 3b side. The light source 9 is a glass substrate 1 in a sensor chip 7 described later.
3 and the required angle of focusing at the boundary between the metal thin films (about 35 to 8
(0 degree) is irradiated with light having a width. Note that the light source 9 may be one that rotates along an arc on the outer periphery of the prism 5 and emits spot light over the above-mentioned angular width. On the other hand, the light receiving device 11 includes a CCD, a photodiode array, and the like.
The reflected light from the boundary corresponding to each angle described above is received, and an electric signal corresponding to the intensity is output.

The cell plate 15 of the sensor chip 7 has a rectangular parallelepiped shape, and a large number of cells 15a are arranged in a matrix at predetermined intervals in the column and row directions. Each cell 15a has a concave shape, and has a shape in which an opening 15b is formed on the bottom surface at the same depth. Each cell 15a is arranged in a matrix of 12 cells in the row direction and 8 cells in the column direction, or a multiple thereof.

On the other hand, the glass substrate 13 of the sensor chip 7
Is a rectangular shape large enough to cover the entire lower surface of the cell plate 15, and a metal thin film (not shown) made of at least one of a gold thin film and a silver thin film is formed on the upper surface by ion plating, sputtering, and vapor deposition. The film is formed on one surface by either of them. Then, the glass substrate 13 is adhered to the cell plate 15 so as to close the opening 15b of each cell 15a, and a different type of sample solution as a specimen is dispensed into each cell 15a. Note that an antibody or a reagent for detecting a specific substance in the sample solution is immobilized in advance on the metal thin film of the glass substrate 13 corresponding to each cell 15a.

Next, the operation of detecting the resonance angles of various types of sample solutions using the sensor chip 7 will be described.

Different kinds of sample solutions (not shown) whose resonance angles are detected are dispensed in advance into each cell 15a of the cell plate 15, whereby the respective sample solutions are adsorbed on the metal thin film in each cell 15a. Have been. And row direction n
In order to detect the resonance angle of the sample solution dispensed in the k-th cell 15a (n and k are arbitrary integers) in the second and column directions, the cell plate 15 is moved in the two-dimensional direction in the row direction and the column direction. Selectively move to cell 15 at desired row and column position
a to the upper surface of the prism 5, and then the cell plate 15
Is moved to the prism 5 side, and the lower surface of the glass substrate 13 (the side on which the metal thin film is not formed) corresponding to the cell 15a is brought into close contact with the upper surface of the prism 5 (see FIG. 1).

At this time, a matching oil or silicon rubber sheet (both not shown) having a refractive index substantially equal to that of the prism 5 and the glass substrate 13 is provided between the upper surface of the prism 5 and the lower surface of the glass substrate 13 corresponding to the cell 15a. By intervening, both can be brought into close contact with each other without air bubbles.

In the above state, with respect to the incident side of the prism 5,
Light from the light source 9 is condensed at a boundary between the glass substrate 13 and the metal thin film, or is irradiated with spot light by rotating over a required angle on a circular arc coincident with the outer peripheral surface of the prism 5 and reflected from the boundary. The light is received by the light receiving device 11 and the intensity of the reflected light is measured to detect a resonance angle at which the intensity of the reflected light is minimum, and therefore, the absorption of the sample solution dispensed into the selected 15a is maximized.

In order to detect the resonance angle of the sample solution dispensed into another cell 15a after the above-mentioned resonance angle detection, the cell plate 15 is moved upward so as to be separated from the upper surface of the prism 5, and After the plate 15 is moved two-dimensionally in accordance with the row and column positions of the cell 15a into which the sample solution for which the resonance angle is to be detected is to be detected, and is opposed to the upper surface of the prism 5, the cell The entire plate 15 is moved downward to bring the lower surface of the glass substrate 13 corresponding to the selected cell 15a into close contact with the upper surface of the prism 5 (see FIG. 3). Then, similarly to the above, light is emitted from the light source 9 to detect the resonance angle of the sample solution in the cell 15a.

In this embodiment, a cell plate 1 in which a number of cells 15a into which different kinds of sample solutions are dispensed is arranged.
5, a glass substrate 13 on which a metal thin film is formed can be attached to form a large number of sensor chips, and the resonance angles of other types of sample solutions can be detected in one operation. The angle detection operation can be made more efficient and the detection time can be reduced. Further, it is not necessary to dispense the sample solution onto the metal thin film every time the resonance angle is detected or to wash the sample solution attached to the metal thin film each time after the detection.

In the above description, each cell 15a in the cell plate 15 and the prism 5 are opposed to each other in a one-to-one relationship to detect the resonance angle of the sample solution. Alternatively, the resonance angles of a plurality of types of sample solutions may be detected.

That is, as shown in FIG. 3, the axial length of the prism 51 having a half-cylindrical cylindrical shape is
Are arranged so as to extend over a plurality of, for example, four cells 15a arranged in such a manner that they can be brought into close contact with the lower surface of the glass substrate 13 corresponding to these four cells 15a at a time. Also, four light sources and light receiving devices (both not shown) are provided on the incident side and the outgoing side of the prism 51, respectively, so that light can be incident on the boundary of the metal thin film on the glass substrate 13 corresponding to each cell 15a. Light reflected from the boundary can be received.

The cell 1 which is in close contact with the upper surface of the prism 51
The number of 5a may be two or eight in addition to the four described above. Further, the light source and the light receiving device may be a single light source and a light receiving device. In this case, a single light coming out of the light source may be split into a plurality of lights having different wavelengths by the splitting means.

In the above description, when detecting the next resonance angle of the sample solution, the operator manually moves the sensor chip 7 selectively in the row direction and the column direction, and the desired sample solution is dispensed. After the cell 15a was made to face the prism 5, the glass substrate 13 corresponding to the cell 15a was brought into close contact with the upper surface of the prism 5, but the sensor chip 7 was attached to a slider (not shown) of a conventionally known three-dimensional moving mechanism. A configuration in which the sensor chip 7 is three-dimensionally moved at the time of selection based on position data set in advance may be employed.

[0023]

According to the present invention, the resonance angles of various kinds of sample components can be efficiently detected.

[Brief description of the drawings]

FIG. 1 is a partially sectional explanatory view schematically showing an SPR device.

FIG. 2 is an exploded perspective view, partly in section, of a sensor chip.

FIG. 3 is a longitudinal sectional view showing a modified embodiment.

[Explanation of symbols]

1 SPR device, 5 prisms, 7 sensor chips,
9 light source, 11 light receiving device, 13 glass substrate, 15
Cell plate, 15a cell, 15b opening

Claims (4)

[Claims] 1. A resonance angle at which an incident side of a prism closely contacting a sensor chip to which a sample solution is adsorbed is irradiated with light of a required angle width and the absorbance of the sample solution becomes maximum due to the intensity of light reflected from the sensor chip. In a surface plasmon resonance angle detection device for detecting and identifying a sample component, a cell plate provided with a large number of cells with open lower surfaces at required intervals, and an opening of each cell with respect to the lower surface of the cell plate. A sensor chip comprising a glass substrate mounted so as to be closed and having a thin metal film formed on the upper surface of each cell. 2. A resonance in which spot light is radiated over a predetermined angle to an incident side of a prism which is in close contact with a sensor chip to which a sample solution is adsorbed, and the absorbance of the sample solution is maximized by the intensity of light reflected from the sensor chip. In a surface plasmon resonance angle detection device that detects an angle and specifies a sample component, a cell plate in which a number of cells whose lower surfaces are open is provided at required intervals, and a lower surface of the cell plate,
A sensor chip, which is attached to close the opening of each cell and comprises a glass substrate having a metal thin film formed on the upper surface of each cell. 3. The sensor chip according to claim 1, wherein the prism has a size capable of being closely attached to a glass substrate facing a single cell. 4. The sensor chip according to claim 1, wherein the prism has a size capable of closely adhering to a glass substrate facing a plurality of cells.