JPS63234156A - Immunity analysis instrument using light and sound - Google Patents

Abstract

PURPOSE:To make accurate measurement by selectively changing over the light beams from plural laser light sources having different wavelengths at every prescribed time to guide said beams into a cell contg. antigens and antibodies and detecting the intensity of acoustic signals by a piezo-electric element according to the change of particle sizes. CONSTITUTION:A light source changing-over means 6 is constituted by mounting plural laser oscillators 7, 7 to a disk 6A. An optical modulator 2a contg. plural modulators is changed over by a frequency changing-over means 8 in synchronization with the change-over of the oscillators 7 to guide the laser beams to the cell 3 in which a sample contg the antigens and antibodies is housed. The oscillators 7 are changed over by the means 6 at every preset time and the acoustic signals obtd. at this time are detected by the piezo-electric elements and are successively processed by a processing system 9. Since the laser light beams of the wavelengths according to the change of particle sizes are entered to the cell, the signals having always the high intensity are obtd. and the execution of the accurate measurement with high sensitivity is permitted.

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Application Field) The present invention relates to an immunoassay device that measures temporal changes in the particle size of aggregates 2 due to antigen-antibody reactions using photoacoustic signals.

(Prior art) Conventional immunoassays use, for example, latex particles as antibodies, add antigen to them, and measure and analyze particles that aggregate over time (the particle size increases). A method using photoacoustic phenomena is known as this measurement and analysis means.

An immunoassay device using this photoacoustic system will be explained with reference to FIG. This generates laser light from a laser oscillator 1, and since this laser light is a single wavelength light, it enters a cell 3 containing an antigen antibody (hereinafter referred to as a sample) as intermittently modulated light by an optical modulator (for example, Choleba). The acoustic signal at that time is converted into an electrical signal, inputted to a lock-in amplifier 4, and recorded on a recorder 5 or the like. The principle of acoustic signal generation is that when the sample is irradiated with intermittent modulated light, intermittent heat is generated due to absorption of the modulated light and thermal relaxation.
This is because a pressure wave (sound wave) having the same frequency as the modulation frequency is generated. Therefore, PZT (
The pressure wave intensity can be detected using a piezoelectric element (piezoelectric element).

Here, light II? It is known that Shintan is the largest, and this makes it possible to detect the particle size from the photoacoustic signal. That is, as shown in Fig. 3, the particle size is 0.1 μ7L 0
．． When changing from 5μm to 1μ, the corresponding frequencies fi and f2.

It exhibits a characteristic where the intensity is highest at f3.

Incidentally, in the case of an argon laser (frequency 0.488 μm), the signal intensity increases significantly when the particle size is 0.3 to 0.8 μm.

(Problems to be Solved by the Invention) However, as mentioned above, although the size of the aggregate changes over time due to antigen-antibody reactions, conventional devices using medium-wavelength light cannot follow said changes. First, there is a problem in that accurate measurements cannot be made. In addition, the photoacoustic signal is independent of the particle size and the concentration (number of particles)
A measurement method focusing on the fact that the intensity changes depending on the difference has been considered, but such a method only works when the serrations of the particles are very large or small compared to the measurement wavelength, and the There was a problem in that it was not possible to measure over a wide range from the concentration range to the high concentration range.

The present invention provides an immunoassay device using photoacoustics that can measure temporal changes in aggregate particle size in response to antigen-antibody reactions with high sensitivity, and can measure over a wide range from low concentration to high concentration. The purpose is to

[Structure of the Invention] (Means for Solving the Problems) In order to achieve the above object, the present invention provides a cell containing an antigen and an antibody by intermittently modulating light from a light source of a specific wavelength via a light modulator. The intensity of the acoustic signal obtained at this time is detected and measured using a piezoelectric element.

The analysis apparatus is characterized in that the light sources are a plurality of light sources each having a different wavelength, and that a light source switching means is provided for selectively switching the light sources at predetermined time intervals.

(Function) In the present invention, since the light source with a plurality of wavelengths is switched so as to mix the light incident on the sample, it is possible to perform measurements with high sensitivity according to changes in particle size.

(Example) Hereinafter, the present invention will be specifically explained with reference to Examples.

FIG. 1 is a block diagram showing one embodiment of the present invention. In the same figure, 6 is a light source switching means, and its rotation axis 6A
A disc 6A is attached to the tip of the disc 6A.
A plurality of laser oscillators 7.7, which are light sources, are attached to the periphery of the laser oscillator 7.7. The plurality of laser oscillators 7 are composed of, for example, semiconductor lasers, each having six different wavelengths (0, 1
μm.

0.5μTIL, 1μm, 2μTIL, 4μ circle, 5
μm...). Reference numeral 2 denotes an optical modulator, which intermittently modulates the laser light from the laser oscillator 7 so that it enters the cell 3 containing the sample. The optical modulator 2 includes a plurality of modulators having frequencies corresponding to the respective wavelengths of the plurality of laser oscillators, and is further provided with a frequency switching means 8, which is synchronized with switching of the laser oscillator 7. It can be switched by Moreover, the cell 3 is made of PZT (
It is made up of piezoelectric elements (piezoelectric elements) and is capable of detecting acoustic signals. The acoustic signal detected by the PZT of the cell is processed in a processing system 9 equipped with a lock-in amplifier and a recorder, as in the prior art.

According to the present invention having the above configuration, after a sample containing an antigen and an antibody is accommodated in the cell 3, the light source switching means 6 is controlled at preset time intervals to increase the wavelength sequentially from a small wavelength (for example, 0.1 μm). The selection of the laser oscillator 7 is changed so that the laser oscillator 7 is selected. At this time, the frequency switching means 8 is operated to periodically select a modulator having the same frequency as the wavelength of the selected laser oscillator. Laser light that is selectively modulated and incident at each time is applied to the sample in the cell 3, and the acoustic signals obtained at this time are detected by the PZT and sequentially processed by the processing system 9. As a result, laser light with a wavelength corresponding to the change in particle size is incident. Therefore, a signal with extremely high intensity can be obtained, and accurate measurements can be made with high sensitivity.

Further, since there is no need to perform measurements based on the concentration difference between low temperature and high concentration as in the conventional method, the intensity of the acoustic signal can be detected over all concentration ranges.

[Effects of the Invention] According to the present invention described in detail above, it is possible to provide an immunoassay device that can perform accurate and highly sensitive measurements because it can perform measurements where the acoustic signal intensity constantly increases. Furthermore, since this measurement can be performed without being affected by concentration, in other words, measurement can be performed over a wide range from a low concentration region to a high a degree region.

[Brief explanation of drawings]

FIG. 1 is a schematic block diagram showing one embodiment of the present invention, and FIG.
The figure is a schematic block diagram of a conventional device, and FIG. 3 is a characteristic diagram showing the relationship between particle size, frequency, and signal intensity. 2... Optical modulator, 3... Cell, 6... Light source selection means, 7... Light source, 8... Frequency selection means, 9...
processing system.

Claims (2)

[Claims] (1) Light from a light source with a specific wavelength is intermittently modulated via an optical modulator and guided to the cell containing the antigen and antibody, and the intensity of the acoustic signal obtained at this time is detected using a piezoelectric element for measurement and analysis. An immunoassay device using photoacoustics, characterized in that the light source is a plurality of light sources each having a different wavelength, and a light source switching means is provided for selectively switching the light sources at predetermined time intervals. (2) The immunoassay device using photoacoustics according to claim 1, wherein the optical modulator includes frequency switching means for switching the modulation frequency in synchronization with selection switching of the light source.