JP2014149305A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer that can achieve stable detection with high S/N ratio even for a minute amount of reaction liquid.SOLUTION: When analyzing an amount of a luminescent substance 112 included in reaction liquid 109 by detecting light from the reaction liquid 109 containing the luminescent substance 112 with a photomultiplier 111 through an optical window 102 to process detected output, an optical system 110 for optical transmission is disposed between the optical window 102 and the photomultiplier 111, the optical system 110 comprising: an entrance aperture facing the optical window; an exit aperture facing a light-receiving face of the photomultiplier 111; and a reflecting face that reflects incident light from the entrance aperture to propagate toward the exit aperture. Thereby, influences of noise induced by temperature from a flow cell 101 are decreased while suppressing decrease in a light quantity from the luminescent substance 112, and analysis with high S/N ratio is achieved.

Description

  The present invention relates to an automatic analyzer for performing qualitative and quantitative measurement of biological samples such as blood and urine.

  The automatic analyzer measures the concentration or presence of a target component in a biological sample such as blood and urine. Compared with the method that is used by laboratory technicians, the analysis speed and analysis accuracy are higher than those used by laboratory technicians. In particular, in the analysis of components present at low concentrations in samples such as thyroid-related substances and infectious disease-related substances, it is necessary to detect faint light with a high S / N (signal-to-noise ratio).

  For example, Non-Patent Document 1 is known as a technique that enables such highly sensitive analysis. In Non-Patent Document 1, a sample to be analyzed is introduced into a temperature-controlled flow cell (hereinafter referred to as a cell) to emit light. The emitted light is received by a photomultiplier tube (photomal) through a cell window glass (optical window) and converted into a current signal, so that a very small amount of light from a sample can be detected. The detector at this time is surrounded by a cooler and cooled, thereby reducing noise and enabling high S / N analysis.

  However, recently, automatic analyzers tend to reduce the amount of reaction liquid flowing in a flow cell in order to reduce inspection costs, and a high S / N analysis technique for such a small amount of liquid is required.

Zenjiro Osawa, Chemiluminescence Basic and Application Examples of Chemiluminescence “4.1 Principles and Equipment of Chemiluminescence Measurement” Maruzen Co., Ltd. (issued on December 30, 2003)

  In Non-Patent Document 1, the noise is reduced by surrounding the detector with a cooler or the like and cooling it. However, the detector is far from the optical window, and the light is not collected enough for a small amount of light emission. I found out.

  Therefore, it is conceivable to maintain a high S / N by suppressing leakage and attenuation of the light amount by reducing the thickness of the optical window and bringing the detector close to the optical window. However, when the detector is close to the flow cell, the heat-derived noise increases due to the temperature effect of the flow cell. Since the flow cell temperature is constantly controlled for stable analysis, noise derived from heat is also suppressed, but the influence on a very small amount of light emission cannot be avoided, making high S / N analysis difficult. .

The present invention relates to an automatic analyzer for detecting and analyzing luminescence from a reaction solution containing a luminescent substance. The object of the present invention is to increase the detection sensitivity of light from the luminescent substance and at the same time the temperature between the flow cell and the detector. It is an object of the present invention to provide an automatic analyzer that reduces the influence and enables stable and high S / N detection even for a small amount of reaction solution.

  A feature of the present invention for achieving the above object is that light from a reaction solution containing a luminescent substance is detected by a light detector through an optical window, and the output of the light detector is processed to be included in the reaction solution. In the automatic analyzer for analyzing the amount of the luminescent substance to be generated, an incident port facing the optical window, an exit port facing the detector light receiving surface, and the incident port between the optical window and the photodetector By providing a light transmission optical system that includes a reflecting surface that reflects light that is incident from and propagates to the exit port, light detection that is less affected by temperature from the flow cell while suppressing a decrease in the amount of light from the luminescent material, and Is where the analysis is possible.

  In addition to the above features, the embodiments to be described later disclose features for more effectively achieving the object, which will be described in detail in the embodiments.

  According to the present invention, it is possible to analyze a very small amount of luminescent material with a high S / N ratio by increasing sensitivity and stabilization, and the reliability and usefulness of an automatic analyzer can be further improved.

1 is a configuration diagram of an automatic analyzer according to a first embodiment of the present invention. Sectional view of the optical transmission optical system according to the first embodiment Illustration of the relationship between the medium and the optical path Explanatory drawing of the optical path which concerns on a 1st Example The figure which shows the change of the signal amount by 1st Example. The figure which shows the temperature influence by 1st Example Configuration diagram of automatic analyzer according to second embodiment of the present invention Sectional view of the optical transmission optical system according to the second embodiment

  Hereinafter, embodiments of the present invention will be described with reference to the illustrated examples. In the embodiment, an example of a cylindrical shape is described as an optical transmission optical system from the optical window to the photodetector, but the shape is limited as long as a reflective surface is formed in the light path. is not.

  FIG. 1 is a block diagram of an automatic analyzer according to a first embodiment of the present invention. The flow cell 101 includes a flow path 103 and an optical window 102. The reaction solution 109 containing the illuminant in the container 108 is sucked into the flow path 103 from the supply port 105 by the pump 107 controlled by the fluid control section 118, and then to the photometry section 104 forming a part of the flow path 103. Introduce.

  The optical window 102 may be any material such as quartz glass or transparent resin as long as the emission wavelength of the phosphor 112 is transmitted and has a thickness of about 2 mm to 5 mm and can withstand the internal pressure of the flow path 103. . The temperature control unit 117 controls the photometry unit 104 with the heater 114 so that the reaction solution has a constant temperature. As the heater 114, any element capable of generating and absorbing heat such as a Peltier element can be used instead. Luminescence of the reaction solution may be started by mixing the reagents or may be started under other conditions, but in any case, the target substance is used by the photometry unit 104 between the start of light emission and the end of light emission. The reaction solution is introduced into the photometry unit 104 via the flow path 103 by the fluid control unit 118 so that the fluorescence is emitted in proportion to the concentration.

  In the reaction solution introduced into the photometry unit 104, the light beam 113 emitted from the phosphor 112 passes through the flow path 103 and the optical window 102, is reflected by the inner surface of the light transmission optical system 110, and propagates to the photomultiplier 111. Then, light is converted into an electrical signal by the photosensitive surface 121 of the photomultiplier. Instead of the photomultiplier 111, an element that converts light such as a photodiode (PD) into an electric signal may be used.

  FIG. 2 shows a cross-sectional view of the optical transmission optical system 110 in the first embodiment. In this embodiment, the optical transmission optical system 110 has a hollow cylindrical shape, and its inner surface 120 is a reflection surface, which reflects the light beam 113 incident from the incident port 122 and emits the light beam 113 from the opposite exit port 123. To do. The emitted light beam 113 is received by the opposing photomultiplier 111. For the sake of explanation, the inner surface of the optical transmission optical system 110 is a reflection surface, but the outer surface may be a reflection surface.

Next, the optical path of light propagating from the reaction solution in the flow cell to the optical transmission optical system through the optical window will be examined. As shown in FIG. 3, consider a light beam that emits light from an arbitrary point (point 0) of the medium 1 (refractive index n1), passes through the medium 2 (refractive index n2), and is emitted to the medium 3 (refractive index n3). In this case, the following formula is established according to Snell's law. (However, in order to simplify the explanation, the light beam is considered in a two-dimensional plane, and the internal angles θ1, θ2, and θ3 are incident angles of the light beam with respect to the normal line of the medium boundary surface.)
n1 * sin θ1 = n2 * sin θ2 (1)
n2 * sin θ2 = n3 * sin θ3 (2)
Here, when the light emission side is air, the optical window is glass, and the optical transmission optical system is air, θ2 and θ3 are given in Table 1 when light rays incident from the point O to the optical window at an angle θ1 = 30 ° are considered. It becomes the angle shown.

  However, since the reaction liquid is introduced into the flow cell in the present embodiment and the medium 1 on the light emission side has a refractive index of 1.3 corresponding to water, θ2 and θ3 are angles shown in Table 2.

  These relationships are shown in FIG. A straight line a indicates an optical path when the light emission side is air, and a straight line b indicates an optical path when the reaction liquid in this embodiment is used. As shown in the figure, when a light beam from a certain point spreads in the same direction, in the flow cell in which the light emission side is a reaction liquid, the light is likely to spread from the central axis to the outside as compared with the case where the light emission side is a gas, and is easily dissipated. It turns out that it will be in a state. Therefore, in this embodiment, as shown in FIG. 1, the incident port 122 of the light transmission optical system 110 is brought into contact with the optical window 102 so that light from the reaction solution is transmitted without being dissipated.

  On the other hand, the light receiving portion of the photomultiplier 111 is made larger than the emission port 123 of the optical transmission optical system 110 so that it can receive light rays emitted at a low angle, thereby preventing light from being dissipated. For example, when the shape of the optical transmission optical system 110 is a hollow cylindrical shape having an outer diameter of about 14 mm and an inner diameter of about 13 mm, the photosensitive surface of the photomaru is about 20 mm in diameter. The mirror substrate 119 may be any material as long as it can hold the reflecting surface 120 such as glass, metal, acrylic, resin, etc. smoothly and stably. The reflective surface 120 is a highly reflective reflector such as a sputter or plating of metal ions such as Al or Au (reflectance, approximately 85%) or a reflective film (several hundred microns, reflectivity of 95% or more). It can be made of materials.

FIG. 5 is a diagram showing changes in the signal amount according to the present embodiment, in the case where the distance from the optical window 102 to the photo 111 is 3.0 mm as a reference (signal amount ratio 1) and the photo 111 is moved away from the optical window 102. It shows the change in signal amount. In this embodiment, since the incident port 122 of the optical transmission optical system is in contact with the optical window 102, there is no light dissipation up to a distance of 3.0 mm, and even when the photo 111 is further away, the reflective film or the metal sputter is used. The amount of signal can be increased according to the present embodiment, whereas the amount of signal is conventionally reduced to 40% due to the action of the reflecting surface formed in (1).

FIG. 6 shows the relationship between the control temperature of the photometric unit 104 of the flow cell 101 and the temperature of the photosensitive surface 121 of the photo 111 when the inner surface 120 of the optical transmission optical system 110 is metal ion sputter and the position of the photo 111 is 9.0 mm. Indicates. Conventionally, it has been confirmed that the temperature of the photomal rises with the control temperature of the flow cell, but according to the present embodiment, the photomal temperature hardly changed. Therefore, according to the present embodiment, the heat insulation effect between the photo 111 and the optical window 102 is enhanced, and it is possible to suppress the noise rise and fluctuation of the photo 111 due to the temperature.

  FIG. 7 shows a second embodiment of the present invention. The flow cell 201 includes a flow path 203 and an optical window 202. The reaction liquid 209 containing the illuminant in the container 208 is sucked into the flow path 203 from the supply port 205 by the pump 207 controlled by the fluid control section 218, and then to the photometry section 204 forming a part of the flow path 203. Introduce. The optical window 202 may be any material such as quartz glass or transparent resin as long as the emission wavelength of the phosphor 212 is transmitted and has a thickness of about 2 mm to 5 mm and can withstand the internal pressure of the flow path 203. . The temperature control unit 217 controls the photometry unit 204 with the heater 214 so that the reaction solution has a constant temperature. As the heater 214, any element that can generate and absorb heat, such as a Peltier element, can be used instead.

  Luminescence of the reaction solution may be started by mixing reagents, or may be started by applying a voltage or the like. In any case, the target substance is detected by the photometry unit 204 between the start of light emission and the end of light emission. The fluid control unit 218 introduces the fluorescence into the photometry unit via the flow path 203 so that the fluorescence is emitted in proportion to the concentration. In the reaction solution, the light beam 213 emitted from the phosphor 212 passes through the flow path 203 and the optical window 202, is reflected on the surface thereof by the optical transmission optical system 210, propagates to the photomultiplier 211, and reaches the photosensitive surface 221 of the photomultiplier. The light is converted into an electrical signal. The photomultiplier 211 is a photodetector that converts light into electrons and multiplies it, but many have a cylindrical structure and have a long and narrow shape. Therefore, the photo 211 protrudes in the direction perpendicular to the flow cell. Therefore, by making the central axis of the optical transmission optical system 210 curved and arranging the central axes of the entrance and the exit in different directions, the entire system can be made compact. The misalignment angle between the axes is preferably within 90 degrees.

  FIG. 8 is a sectional view of the optical transmission optical system 210 in the second embodiment. The optical transmission optical system 210 has a hollow shape, and the inner surface 220 is a reflecting surface, which reflects the light beam 213 incident from the incident port 222 and emits the light beam 213 from the opposite exit port 223. Although the reflection surface is the inner surface 220 for explanation, it may be the outer surface side of the optical transmission optical system 210. The emitted light beam 213 is received by the facing photo 211.

Similar to the first embodiment, the optical window 202 and the incident port 222 are arranged in contact with each other to prevent light dissipation, and the light receiving portion of the photo 211 is larger than the output port 223 so that the light beam emitted at a low angle can be emitted. Is also configured to receive light.

  The mirror base material 219 may be any material as long as it can hold the reflective surface 220 of glass, metal, acrylic, resin, etc. smoothly and stably. The reflective surface 220 is a highly reflective reflector such as a sputter or plating of metal ions such as Al or Au (reflectance, approximately 85%) or a reflective film (several hundred microns, reflectivity of 95% or more). It can be made of materials. When it is difficult to form a curved surface with a reflective film, the optical transmission optical system 210 may be manufactured by dividing it into a plurality of parts for each refracting portion.

  As described above, according to this embodiment, the central axis 224 of the optical transmission optical system 210 can be curved, so that it can be made compact in accordance with the system configuration of the automatic analyzer. High S / N analysis can be performed even for a small amount of reaction solution without impairing the stabilization and stabilization.

101, 201 ... flow cell 102, 202 ... optical window 103, 203 ... flow path 104, 204 ... photometry section 105, 205 ... supply port 106, 206 ... discharge port 107, 207 ... Pumps 108, 208 ... Vessels 109, 209 ... Reaction liquids 110, 210 ... Optical transmission optical systems 111, 211 ... Photomals 112, 212 ..Phosphors 113, 213 ... Light rays 114, 214 ... heaters 119, 219 ... mirror base material 120, 220 ... reflective surface (inner surface)
122, 222... Entrance 123, 223... Exit 124, 224 .. central axis of optical transmission optical system

Claims (5)

A flow path for flowing a reaction solution containing a luminescent substance;
A temperature control unit for controlling the flow path temperature;
An optical window that allows light from a luminescent material that spreads in the reaction solution to pass through ;
Before SL and a photomultiplier tube for detecting the light passing through the optical window,
In an automatic analyzer that processes the data from the photomultiplier tube and analyzes the amount of the luminescent substance contained in the reaction solution,
An entrance facing the optical window;
An exit opening facing the light receiving surface of the photomultiplier;
A hollow portion having the entrance at one end and the exit at the other end ;
The light from the light-emitting substance that has entered from the entering morphism port is provided an optical transmission optical system comprising a reflecting surface which propagates to said exit by reflecting on the inner surface covered with anti Ysaÿe of the hollow portion,
The entrance of the optical transmission optical system is disposed in contact with the upper surface of the optical window,
The automatic analyzer is characterized in that the size of the light receiving surface of the photomultiplier tube is larger than the size of the exit port facing the photomultiplier tube. The automatic analyzer according to claim 1, wherein
A part of the flow path constitutes a photometric part for starting light emission of the luminescent substance contained in the reaction solution introduced into the flow path,
The optical window is provided between the photometry unit and the optical transmission optical system,
The automatic analyzer is characterized in that the size of the entrance of the optical transmission optical system is larger than that of the photometry unit. The automatic analyzer according to claim 1, wherein
The automatic analyzer according to claim 1, wherein an emission port of the optical transmission optical system is disposed apart from a light receiving surface of the photomultiplier tube. The automatic analyzer according to claim 1, wherein
The optical transmission optical system is composed of the hollow portion having a cylindrical shape and the reflection surface formed on the inner surface thereof.
The automatic analyzer according to claim 1, wherein the hollow portion, the entrance, and the exit are arranged on the same axis. The automatic analyzer according to claim 1, wherein
The optical transmission optical system is composed of the hollow portion having a cylindrical shape and the reflection surface formed on the inner surface thereof.
An automatic analyzer characterized in that the hollow portion has a curved shape and is arranged with the central axes of the entrance and the exit facing in different directions.

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