JPH073388B2 - Film thickness change measuring device - Google Patents

Description

TECHNICAL FIELD The present invention relates to an apparatus for measuring a change in film thickness. More specifically, an antigen or an antibody is immobilized on a plate, and the plate is brought into contact with a test solution, and an interference color useful when detecting an antibody or an antigen in quarantine using an antigen-antibody reaction is used. The present invention relates to a film thickness change measuring device using the.

[Prior Art] In recent years, in the field of medical diagnosis, an antigen or an antibody is immobilized on a carrier such as a plate, and the carrier is brought into contact with a test solution, so that the antibody is carried when the antigen is carried, When the antibody is carried, it is attempted to react the antigen and measure the presence or absence of the antibody or the antigen in the test liquid or the concentration thereof.

Among these, the carrier is a light-reflecting flat plate, and the antibody (or antigen) is carried thereon, and the antigen (or antibody) against it.
A method of measuring the above reaction as a change in film thickness on the flat plate has been proposed as a simple method. When a light beam is applied to this flat plate, the incident light beam is decomposed into a part that is reflected by the surface and a part that is reflected by the light reflective flat plate, and the optical path difference corresponding to the film thickness causes interference in the reflected light. Interference color appears. Therefore, the change in the film thickness can be detected as the change in the interference color. (For example, refer to JP-A-59-160763, JP-A-51-148015, JP-A-58-195142, etc.).

By the way, it is also possible to use a conventionally known color / color difference meter (for example, a color color difference meter CR-200, manufactured by Minolta Co., Ltd.) to measure the change in the interference color. The meter receives the light ray reflected vertically from the surface to be measured and converts it by the color system, which is inconvenient for the above purpose. This is because the above-described color change of the interference color is most sensitively sensed in the case of incident light / reflected light having a considerable angle from the perpendicular of the surface to be measured.

In addition, the sample mounting unit includes a light projecting unit that projects light through the optical filter of the light source onto the sample and a light receiving unit that receives reflected light or transmitted light from the sample. The light projecting unit and the light receiving unit are provided vertically independently of each other. There is also known a device which is configured to be rotatable around a table so that gloss measurement and color measurement can be performed at the same time (JP-A-58-122448). However, this apparatus is also unsuitable for the above-mentioned measurement because the sample mounting table is vertical.

[Problems to be Solved by the Invention] Therefore, the present inventor studied to improve a conventionally known color / color difference meter so as to meet the above-mentioned purpose, and carried out measurement on a surface of a horizontal flat plate (e). An optical fiber for light irradiation (a) capable of irradiating parallel rays at an incident angle (θ ₁ ) of 20 ° or more from the tip to the plane (c) of the object, and the same angle as the incident angle (θ ₁ ) at the tip A light receiving optical fiber (b) capable of receiving reflected light at a reflection angle (θ ₂ ) of
Illumination means is connected to the other end of the light irradiation optical fiber (a), and the other end of the light receiving optical fiber (b) is
The invention has invented a reflection color measuring device which is connected to an optical sensor and measures the color difference with the optical sensor.

However, this device, as a test sample in the form of a flat plate, fixes various light sources and antibodies in the same flat plate at different positions, and contacts these with a test liquid to simultaneously detect the presence or absence of various antibodies and antigens. It is still inconvenient when trying to detect the amount, and it is not practical as an apparatus for measuring the change in film thickness.

It is an object of the present invention to provide a film thickness change measuring apparatus which solves the problem described in detail and is excellent in practicability and capable of measuring a plurality of objects to be measured.

[Means for Solving the Problem] The present invention has an incident angle (θ ₁ ) of 20 ° or more with respect to a plane (c) of a horizontal flat plate (e) carrying an object to be measured from its tip.
Where a substantially parallel light beam can be emitted at the other end, a light irradiation optical fiber (a) having an illuminating means connected to the other end, and at the tip thereof, the angle of incidence (θ ₁ ) is substantially the same as the incident angle (θ ₁ ) from the plane (c). A light receiving optical fiber (b) for receiving the reflected light reflected at the reflection angle (θ ₂ ) and delivering the received light to the optical sensor, and a flat plate (e) carrying the object to be measured can be set, and the flat plate (E) A flat plate setting jig (f) capable of displacing and irradiating the desired range with light, and the magnitude of the displacement are measured, and the magnitude of the displacement and the measured value of the reflected light at the position are measured. A film thickness characterized by having a display means (g) for displaying in correspondence with each other and making the optical fiber (a) and the optical fiber (b) interlock while maintaining the relationship of θ ₁ ≈θ _2. It is a change measuring device.

Thus, various antigens and antibodies were fixed on the plate (e) set horizontally and fixed, and this was brought into contact with the test liquid to cause an antigen-antibody reaction on the plate to be measured. With respect to an object, it is possible to accurately and efficiently measure a change in film thickness, and to detect the presence or absence and concentration of an antibody or an antigen.

[Embodiment] Hereinafter, the device of the present invention will be specifically described with reference to the examples of the drawings.

FIG. 1 is a conceptual diagram showing a detection end of a measuring device of the present invention, and FIG. 2 is a conceptual diagram showing the entire device. In the figure, (a) is an optical fiber for irradiating light (optical fiber for illumination), whereby parallel rays are incident at an incident angle θ ₁ with respect to a plane (c) on a horizontal flat plate (e) carrying an object to be measured. Is irradiated. The incident angle θ ₁ is set to 20 ° or more from the viewpoint of ease of measurement and accuracy. In this figure, the optical fiber for light irradiation (a)
Has its tip facing the plane (C) and the other end connected to a diffusion chamber containing a lamp as a lighting means. That is, the lamp as the illumination means is provided in the diffusion chamber, and the light beam emitted from the lamp is transmitted to the optical fiber (a) most effectively and used for irradiation. A light receiving optical fiber (measuring optical fiber) (b) is provided opposite to the light irradiating optical fiber (a), and these light beams are radiated at an incident angle θ ₁ and are reflected at an angle θ ₂ approximately the same. In contrast, it is installed to receive the reflected light.

The other end of the light receiving optical fiber (b) is connected to an optical sensor (not shown), and the received light beam is delivered to the optical sensor.

At the time of measurement, optical interference occurs on the flat plate (e) carrying the object to be measured at the center point (point A) where the incident ray direction and the reflected ray direction intersect on the plane (c). The position can be changed by moving the flat plate setting jig (f), and measurement at a plurality of measurement points is possible. In the example of FIG. 1, a flat plate setting jig (f)
Can move horizontally in the front-back direction (perpendicular to the plane of the paper), which allows you to measure the interference light at each position in the front-back direction (direction perpendicular to the plane of the paper) on the flat plate (e) to be measured. it can.

At this time, the displacement of the flat plate setting jig (f) is detected by a known displacement measuring means, and the displacement amount and the measurement value of the reaction light are displayed in correspondence on the display means (g). This display means (g) may be displayed on the screen,
Preferably, the displacement amount and the measured value are printed out in correspondence with each other.

As described above, by measuring while moving the flat plate (e), it is possible to efficiently detect the presence or absence of various antibodies or antigens and their amounts.

FIG. 2 shows an example of the device of the present invention.
Is the entrance of the flat plate setting jig (f). From here, a flat plate (e) is placed and set on the jig (f), and the jig (f) is manually or automatically displaced in the horizontal plane to obtain a plurality of objects to be measured. But it can be easily measured.

In the present invention, since the light irradiator and the light receiver can be configured by the optical fibers (a) and (b) respectively, the tip of the optical fiber is separated from the illumination lamp and the preferred location for operation near the entrance (h). Can be installed in

In the figure, (i) is a micro-computer part for converting the reflected light transmitted from the light-receiving optical fiber (ii) as a measured value, and the display means of (i) shows the conversion result in response to the displacement of the flat plate (e). It is the part that is displayed by printing.

In the present invention, the optical fiber for light irradiation (a) and the optical fiber for light reception (b) can be moved up and down with the tips thereof facing the center A of the plane (c) of the object to be measured, thereby facilitating θ ₁ Incident angle (θ ₁ ) while maintaining the relationship of ≈ θ ₂
And the reflection angle (θ ₂ ) can be changed in conjunction with each other. Therefore, the interference color can be measured with the incident angle (θ ₁ ) and the reflection angle (θ ₂ ) most suitable for the object to be measured.
The sensitivity of the measurement is also extremely high.

In this way, the received light beam is represented by an appropriate color system by a conventionally known method. For example, if the L ^* a ^* b ^* color system recommended by the CIE as a uniform perceptual color space is used, ΔE ^* ab = [(ΔL ^* ) ² + (Δa ^* ) ² + (Δb ^* ) ² ] ^{1 The} color difference is represented by ^{/ 2} , and using the UCS color system, the color difference is represented by ΔU ¹ V ¹ = [(ΔU ¹ ) ² + (ΔV ¹ ) ² ] ^1/2 .

However, the reflected light does not necessarily have to be measured by color difference,
You may measure by the difference of the brightness of monochromatic light.

[Effects of the Invention] According to the measuring device of the present invention as described above, the presence or absence and the concentration of an antigen or an antibody are measured by measuring the change in film thickness of a plurality of objects to be measured supported on a horizontal flat plate. Can be measured with high sensitivity and efficiency, which is extremely practical.

[Brief description of drawings]

FIG. 1 is a detection end of a reflected light measuring device of the present invention, and FIG. 2 is a conceptual diagram showing the entire device. In the figure, (a) is an optical fiber for light irradiation, (b) is an optical fiber for receiving light, (c) is a flat surface of the object to be measured, (e) is a horizontal flat plate carrying the object to be measured, and (f) is a flat plate set. jig,
(G) is a display means, (H) is a flat plate setting jig entrance,
(I) represents the microcomputer part. Further, A in FIG. 1 represents the center of the plane of the object to be measured, θ ₁ is the incident angle of the light beam, θ ₂ is the reflection angle of the light beam, and θ ₁ ≈θ ₂ ≧
It is 20 °.

Claims (1)

[Claims] 1. A device capable of irradiating a substantially parallel light beam from its tip with respect to a plane (c) of a horizontal flat plate (e) carrying an object to be measured at an incident angle (θ ₁ ) of 20 ° or more. , An optical fiber for light irradiation (a) having illumination means connected to the other end, and an incident angle (θ ₁ ) from the plane (c) at the tip thereof
Set a light receiving optical fiber (b) for receiving the reflected light reflected at a reflection angle (θ ₂ ) substantially the same as the above and delivering the received light beam to the optical sensor, and a flat plate (e) carrying the DUT. A flat plate setting jig (f) capable of displacing the flat plate (e) and irradiating the flat plate (e) with light in a desired range, and measuring the size of the displacement of the flat plate (e), The optical fiber (a) and the optical fiber (b) are interlocked with each other while having a display means (g) for displaying the measured value of the reflected light at the position in association with each other while maintaining the relationship of θ ₁ ≈θ _2. A film thickness change measuring device characterized in that