WO2019232699A1 - 自校准的弱光检测装置及其应用 - Google Patents

自校准的弱光检测装置及其应用 Download PDF

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Publication number
WO2019232699A1
WO2019232699A1 PCT/CN2018/090005 CN2018090005W WO2019232699A1 WO 2019232699 A1 WO2019232699 A1 WO 2019232699A1 CN 2018090005 W CN2018090005 W CN 2018090005W WO 2019232699 A1 WO2019232699 A1 WO 2019232699A1
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Prior art keywords
light
self
detection device
diaphragm
diffuse reflection
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PCT/CN2018/090005
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English (en)
French (fr)
Inventor
张震
何太云
刘奇林
陈建平
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深圳迎凯生物科技有限公司
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Priority to EP18921700.3A priority Critical patent/EP3779412A4/en
Priority to PCT/CN2018/090005 priority patent/WO2019232699A1/zh
Publication of WO2019232699A1 publication Critical patent/WO2019232699A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/0271—Housings; Attachments or accessories for photometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G01J1/0407—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings
    • G01J1/0411—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings using focussing or collimating elements, i.e. lenses or mirrors; Aberration correction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G01J1/0407—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings
    • G01J1/0437—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings using masks, aperture plates, spatial light modulators, spatial filters, e.g. reflective filters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G01J1/0407—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings
    • G01J1/0474—Diffusers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/08—Arrangements of light sources specially adapted for photometry standard sources, also using luminescent or radioactive material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
    • G01J1/4228—Photometry, e.g. photographic exposure meter using electric radiation detectors arrangements with two or more detectors, e.g. for sensitivity compensation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G01J2001/0481—Preset integrating sphere or cavity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/08—Arrangements of light sources specially adapted for photometry standard sources, also using luminescent or radioactive material
    • G01J2001/086—Calibrating drift correction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence

Definitions

  • the invention relates to the technical field of chemiluminescence immunodetection equipment, in particular to a self-calibrating low-light detection device.
  • Chemiluminescence immunoassay belongs to the category of low-light detection. Temperature changes in the environment often cause problems such as temperature drift of the low-light detection device, resulting in inconsistent responses of the low-light detection device to the same standard signal light. In addition, the response of the low-light detection device may change due to factors such as device aging. In order to solve the problems of temperature drift and aging, traditional weak light detection devices mostly use complex calibration optical path systems, such as various mirrors, beam splitters, and filters. Some calibration optical systems use multiple flat mirrors to reflect light. The angle change is twice the angle change of the mirror. For the weak light detection device, its slight change will greatly change the number of photons, which will directly affect the accuracy of the calibration. Moreover, this type of device has a complicated structure and high cost. , Assembly and commissioning requirements are high, mass production efficiency is low, and the complex structure increases its risk factor of instability.
  • a self-calibrating low-light detection device including:
  • the box includes a reference room, a front room, and a detection room connected to the front room;
  • the signal optical system includes a signal light collector and a photon counting module.
  • the signal light collector and the photon counting module are sequentially arranged along the signal light emission direction.
  • the signal light collector is located in the front room.
  • the photon counting module is located in the detection. Room; and
  • the reference optical system is used for the calibration of the signal optical system.
  • the reference optical system includes a diffuse reflection cavity, a reference light source and a photodetector provided in the diffuse reflection cavity, a photoelectric control board electrically connecting the reference light source and the photodetector, and The diaphragm connecting the photon counting module and the diffuse reflection cavity, and the photoelectric control board is electrically connected to the photon counting module; the diffuse reflection cavity, the reference light source, the photodetector and the photoelectric control board are installed in the reference room, and the diaphragm connects the detection room and the reference room.
  • the light from the light source is diffusely reflected in the diffuse reflection cavity, enters the signal optical system through the diaphragm, and is projected to the photon counting module.
  • FIG. 1 is a schematic diagram of a preferred embodiment of a self-calibrating low-light detection device
  • FIG. 2 is a cross-sectional view of the self-calibrated low-light detection device of FIG. 1 along the A-A direction;
  • FIG. 3 is a partial schematic diagram of a self-calibrated low-light detection device including a reference optical system in FIG. 2;
  • FIG. 3 is a partial schematic diagram of a self-calibrated low-light detection device including a reference optical system in FIG. 2;
  • FIG. 4 is an enlarged schematic view of part B of the low-light detection device of the self-calibration of FIG. 2.
  • the self-calibrated low-light detection device 100 is applied to chemiluminescence immunoassay. When applied, the self-calibrated low-light detection device 100 is optically connected to a reaction container that can generate an optical signal in the reading room. In one embodiment, once the reaction container enters the reading room, the shutter provided near the reaction container is closed to shield the ambient light around the reaction container. In one embodiment, the reaction container is disposed on the hole of the tray body and can rotate with the tray body. The tray body is located in a containing body, and the tray body and the containing body together form a reading room. When taking a reading, the reaction container rotates with the pan to the reading station.
  • the optical signal in the reaction container is generated by the chemiluminescence of the reactants in the reaction container, such as the chemiluminescence reaction of the direct light emitting compound acridine ester in the corresponding pre-excitation solution and the excitation solution.
  • a self-calibrating low-light detection device 100 includes a cabinet 10, a signal optical system 20 and a reference optical system 30 installed in the cabinet 10.
  • the cabinet 10 is mainly used for
  • the signal optical system 20 is used to collect the signal light and convert it into an electrical signal.
  • the reference optical system 30 provides a standard light source for calibration and is used for drift calibration of the signal optical system 20 to adjust the detection result to make the detection The results are more accurate.
  • the cabinet 10 includes a front room 11, a detection room 12 connected to the front room 11, and a reference room 13 connected to the signal optical system 20.
  • the front room 11 is adjacent to and connected to the reading room.
  • the signal optical system 20 includes a signal light collector 21 and a photon counting module 22.
  • the signal light collector 21 and the photon counting module 22 are sequentially disposed along a signal light emitting direction.
  • the signal light collector 21 is disposed on the front.
  • the chamber 11 and the photon counting module 22 are provided in the detection chamber 12.
  • the collector 21 is imaged on the photosensitive surface of the photon counting module 22, and the size of the imaging surface just covers the photosensitive surface, or the imaging surface is slightly smaller than the photosensitive surface, so that stray light other than the non-light emitting surface cannot enter the photon counting module 22, thereby reducing interference light Or background light interference. It can be understood that the position of the signal light collector 21 in the front room 11 can be adjusted, that is, the distance between the signal light collector 21 and the photon counting module 22 can be adjusted, so that the imaging surface better covers the photosensitive surface, and noise interference is reduced to lowest.
  • the signal light collector 21 is a single convex lens.
  • the convex lens has the function of concentrating light.
  • the light from the light-emitting surface can be imaged and projected onto the photosensitive surface of the photon counting module 22.
  • the convex lens has a fixed focal length and is easy to adjust the imaging.
  • a single convex lens can further simplify the structure of the device and save costs.
  • the signal light collector 21 may also be a lens group consisting of a plurality of convex lenses, a lens group consisting of a convex lens and a concave lens, or an optical fiber. Surface effect.
  • the photon counting module 22 includes a detector 23, and the detector 23 may be an end-window type photomultiplier tube (PMT) or a similar device capable of converting a weak light signal into an electrical signal working in a counting mode.
  • the device, the photomultiplier tube has high sensitivity and fast response speed, and can quickly obtain measurement results.
  • the photon counting module 22 may further include a photon counting board 24, and the detector 23 is mounted on the photon counting board 24 through a mounting base.
  • the photon counting board 24 is further provided with a voltage dividing circuit, a high voltage module, a high gain signal amplifier, and a discrimination. Converter, prescaler, data processor, etc.
  • the prescaler is connected to a data processor for counting photon pulses.
  • the prescaler also has the function of pulse shaping, making the pulse signal more ideal.
  • Optical signals such as emitted optical signals generated from the reference optical system 30 and the reaction solution in the reaction container, can be irradiated onto the detector 23.
  • the reference optical system 30 includes a diffuse reflection cavity 31, a reference light source 32 and a photodetector 33 provided in the diffuse reflection cavity 31, a photoelectric control board 34 that electrically connects the reference light source 32 and the photodetector 33, and communicates therewith.
  • the signal optical system 20 is electrically connected to the diaphragm 35 and the photoelectric control board 34 of the diffuse reflection cavity 31 and is connected to the photon counting module 22.
  • the photon counting module 22 is mainly used to control and monitor the light intensity of the reference light source 32.
  • the diffuse reflection cavity 31, the reference light source 32, the photodetector 33, and the photoelectric control board 34 are all installed in the reference room 13.
  • the reference room 13 communicates with the signal optical system 20 through the diaphragm 35.
  • the light from the reference light source 32 is inside the diffuse reflection cavity 31. After diffuse reflection, it enters the signal optical system 20 through the diaphragm 35 and is projected onto the photosensitive surface of the photon counting module 22 and detected by the photon counting
  • the diffuse reflection cavity 31 is a cylindrical cavity, and adjacent inner sidewalls of the cylindrical cavity are perpendicular to each other, so that the diffusely reflected light is refracted and reflected multiple times, the optical path is increased, and a variety of different lights are obtained.
  • the diffused reflection light of the process can make the outgoing light from the diffuse reflection cavity 31 more uniform and random, and improve the tolerance of the optical system to manufacturing variation.
  • the reference light source 32 and the photodetector 33 are installed on the same side in the diffuse reflection cavity 31, and the photodetector 33 is mounted on the photoelectric control board 34 at a lower height than the reference light source 32, so that the reference light source can be minimized.
  • the direct light of 32 is projected onto the photodetector 33, which effectively improves the tolerance of the photodetector 33 to the difference in the positioning of the reference light source 32.
  • the diaphragm 35 is located on the side opposite to the reference light source 32, and a longer optical path can be obtained, which further reduces the light intensity of the light projected onto the diaphragm 35.
  • a light blocking device 36 is provided in the diffuse reflection cavity 31.
  • a light blocking device 36 is provided on the side of the diffuse reflection cavity 31 near the diaphragm 35, and a light passing channel 37 is provided above the light blocking device 36. Part of the light from the reference light source 32 passes through the light passing channel 37 after diffuse reflection. It enters the diaphragm 35 and is projected onto the photon counting module 22.
  • the light blocking device 36 is a vertical plate for blocking the direct rays of the reference light source 32 from entering the diaphragm 35, ensuring that the light passing through the diaphragm 35 is diffusely reflected, and avoiding projection of photons through the diaphragm 35 to photons The optical signal of the counting module 22 is too large and the photon counting module 22 is damaged.
  • the light blocking device 36 may have other structures as long as it can block the direct light of the reference light source 32 from entering the diaphragm 36.
  • the light-passing channel 37 may be formed between the light-blocking device 36 and the diffuse reflection cavity 31, for example, a light-passing channel 37 is formed between the side of the light-blocking device 36 and the cavity wall of the diffuse-reflection cavity 31;
  • a light-passing channel 37 is set on the light-blocking device 36, and the light-passing channel 37 may be a light-passing gap or an aperture.
  • the inner wall of the diffuse reflection cavity 31 is coated with a diffuse reflection coating or matte glass to obtain a better diffuse reflection effect.
  • the spectrum of the reference light emitted by the reference light source 32 basically matches the spectral characteristics of the signal light detected by the photon counting module 22, so that the possibility of detection differences due to the spectral response of various PMT changes can be minimized.
  • the reference light source 32 is green light, for example, when the signal light is a light-emitting signal generated by a chemical reaction of the spiral adamantane and its derivative in the reaction container.
  • the reference light source 32 may also be blue light, for example, when the signal light is a light-emitting signal generated by a chemical reaction of the acridinium ester in the reaction container.
  • the reference light source 32 is an LED light or an OLED light.
  • the LED light and the OLED light are easy to control, and the light is stable. They can be used as standard light sources, and they are all surface light. Concentration and most of the light reflected in the same direction, contrary to the original intention of diffuse reflection.
  • the diaphragm 35 is a small circular hole provided on the side wall of the detection chamber 12, the diaphragm 35 communicates with the detection chamber 12 and the reference chamber 13, and the light from the reference light source 32 is diffused. After diffuse reflection in the reflection cavity 31, it enters the signal optical system 20 through the diaphragm 35 and is projected to the photon counting module 22.
  • the reference light may also pass through the signal light collector 21 and then be projected onto the detector 23.
  • the diaphragm 35 may be a circular opening on the side wall of the front chamber 11, and the signal may be corrected. The effect of the light collector 21 on the signal light collection.
  • the diaphragm 35 communicates with the front room and the reference room.
  • the light from the reference light source 32 is diffusely reflected in the diffuse reflection cavity 31 and enters the signal optical system 20 through the diaphragm 35 and is projected to the photon.
  • Counting module 22 is also pass through the signal light collector 21 and then be projected onto the detector 23.
  • the diaphragm 35 is a circular small hole, and the diameter of the circular hole is 1 to 10 mm.
  • the diaphragm 35 may also be any entity that restricts the light beam in the optical system, such as a hard opaque material provided with a light transmitting hole.
  • the setting of the diaphragm 35 can ensure that only a small part of the emitted light of the reference light source 32 is projected to the photon counting module 22, so as to avoid exceeding the measurement range of the photon counting module 22 and even causing damage to the device.
  • the reference light entering and exiting the diaphragm 35 is random diffusely reflected light, which prevents the emitted light of the reference light source 32 from directly incident on the detector of the photon counting module 22, which can effectively reduce the change in the installation position of the reference light source 32 to the calibration result. Caused by inaccuracies.
  • the diffuse reflection cavity 31 and the diaphragm 35 change and attenuate the emitted light of the reference light source 32, which not only avoids the use of various optical devices such as diffusion plates, attenuating plates, and mirrors in the prior art, simplifies the structure, and saves costs.
  • the tolerance of the self-calibrated low-light detection device 100 to variations in the manufacturing process can also be improved, that is, the low-light detection device 100 of the present invention does not require high assembly accuracy of the reference light source 32.
  • the photodetector 33 is a photodiode (PD, Photodiode) or avalanche photodiode (APD, Avalanche photodiode), or other similar devices capable of converting optical signals into electrical signals.
  • the photodetector 33 is used to monitor and feedback adjust the light intensity change of the reference light source 32.
  • the reference optical system 30 is used for calibrating the signal optical system 20, and the output light intensity of the reference light source 32 is adjusted through feedback and control of the photoelectric control board 34. After the light emitted by the reference light source 32 is diffusely reflected in the diffuse reflection cavity 31, part of the light is emitted. The light is detected by the photodetector 33, and a small part of the light is projected to the photon counting module 22 through the diaphragm 35. According to the structural characteristics of the diaphragm 35 and the diffuse reflection cavity 31, the light signal of the light of the reference light source 32 with a specific light intensity passing through the diaphragm 35 can be quantified.
  • the light signal passing through the diaphragm 35 is not disturbed by external factors, and the photoelectric detection The light signal received by the detector 33 is directly proportional to the light signal received by the photon counting module 22 through the diaphragm 35. In this way, the light signal received by the photon counting module 22 of the reference light source 32 can be accurately measured indirectly through the photodetector 33 at the same time.
  • the photodetector 33 and the light signal received by the photon counting module 22 through the diaphragm 35 is S0.
  • the output light intensity of the reference light source 32 is controlled by the photoelectric control board 34 to be X-ray intensity. It is measured that the light signal received by the photodetector 33 and received by the photon counting module 22 through the aperture 35
  • the ratio of the optical signal of S1 is S1, which is compared with S0 before the drift to obtain the calibration factor F.
  • the optical signal Z is calibrated and calculated to obtain an accurate reactant optical signal in the reaction container, thereby achieving the effect of self-calibration.
  • the cabinet 10 communicates with the reading room to achieve sealing, and external light cannot penetrate into the cabinet 10 to avoid interference from external light.
  • the combination of the signal optical system 20 and the reference optical system 30 reduces the probability that the photon counting module 22 is affected by various factors and causes inaccurate measurement data.
  • the reference optical system 30 adopts an integrating sphere-like structure, and the output light is a diffusely reflected light instead of direct light, which can improve the stability of the reference light source, does not require complex optical devices, and improves calibration accuracy while reducing complex
  • the structure improves the stability, and the structure is simple, the weight is small, and the manufacturing requirements are low. The cost of the device is greatly saved on the basis of ensuring stability and performance.

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  • General Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

一种自校准的弱光检测装置，具有箱体，其内包括光子计数模块和参考光学系统，参考光学系统用于信号光学系统的校准，包括漫反射腔、设于漫反射腔内的参考光源与光电探测器、光电控制板及连通光子计数模块与漫反射腔的光阑，光电控制板电连接参考光源、光子计数模块与光电探测器，光阑连通检测室与参考室。

Description

自校准的弱光检测装置及其应用 技术领域
本发明涉及化学发光免疫检测设备技术领域，尤其指自校准的弱光检测装置。
背景技术
化学发光免疫检测属于弱光检测范畴，环境的温度变化往往会使弱光检测装置产生温度漂移等问题，导致弱光检测装置对同一标准信号光的响应不一致。此外，由于器件老化等因素也会导致弱光检测装置的响应发生变化。传统的弱光检测装置为了解决温漂和老化等问题大多采用复杂的校准光路系统，如各种反射镜、分光镜、滤光片等，一些校准光学系统采用多片平面反射镜，反射光的角度变化是反射镜角度变化的2倍，对于微弱光检测装置，其微小的变化将对光子数发生较大的变化，这将直接影响校准的准确性，而且，这类装置结构复杂、成本高、装配和调试要求高、批量生产效率低，并且复杂的结构增加其不稳定性的风险系数。
发明内容
根据本申请的各种实施例，提供一种自校准的弱光检测装置，包括：
箱体，箱体包括参考室、前置室及连通前置室的检测室；
信号光学系统，信号光学系统包括信号光收集器和光子计数模块，信号光收集器和光子计数模块沿信号光的发射方向依次设置，信号光收集器设于前置室，光子计数模块设于检测室；及
参考光学系统，参考光学系统用于信号光学系统的校准，参考光学系统包括漫反射腔、设于漫反射腔内的参考光源与光电探测器、电连接参考光源 与光电探测器的光电控制板及连通光子计数模块与漫反射腔的光阑，光电控制板电连接光子计数模块；漫反射腔、参考光源、光电探测器及光电控制板安装于参考室，光阑连通检测室与参考室，参考光源的光线在漫反射腔体内漫反射后通过光阑进入信号光学系统，并投射至光子计数模块。
本发明的一个或多个实施例的细节在下面的附图和描述中提出。本发明的其它特征、目的和优点将从说明书、附图以及权利要求书变得明显。
附图说明
为了更好地描述和说明这里公开的这些发明的实施例和/或示例，可以参考一幅或多幅附图。用于描述附图的附加细节或示例不应当被认为是对所公开的发明、目前描述的实施例和/或示例以及目前理解的这些发明的最佳模式中的任何一者的范围的限制。
图1为自校准的弱光检测装置的一较佳实施例的示意图；
图2为图1自校准的弱光检测装置沿A-A方向的剖视图；
图3为图2自校准的弱光检测装置中的含有参考光学系统的局部示意图；
图4为图2自校准的弱光检测装置的B部分的放大示意图。
具体实施方式
为了便于理解本发明，下面将参照相关附图对本发明进行更全面的描述。附图中给出了本发明的较佳实施例。但是，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使对本发明的公开内容的理解更加透彻全面。
需要说明的是，当元件被称为“固定于”另一个元件，它可以直接在另一个元件上或者也可以存在居中的元件。当一个元件被认为是“连接”另一个元件，它可以是直接连接到另一个元件或者可能同时存在居中元件。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用 的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。
自校准的弱光检测装置100应用于化学发光免疫检测，应用时自校准的弱光检测装置100光学连通于读数室内的可产生光学信号的反应容器。在一个实施例中，一旦反应容器进入读数室，设置在反应容器附近的快门关闭，遮蔽反应容器周围的环境光。在一个实施例中，反应容器设置于盘体的孔位上，可随盘体转动，盘体位于一容置体内，盘体和容置体一起构成读数室。读数时，反应容器随盘体转动到读数工位。本领域技术人员可以理解，反应容器内的光学信号由反应容器内的反应物发生化学发光发应产生，比如直接发光类化合物吖啶酯在相应的预激发液和激发液中发生的化学发光反应，化学发光底物螺旋金刚烷及其衍生物在碱性磷酸酶催化下的化学发光反应等。
请参阅图1至图4，一较佳实施例的自校准的弱光检测装置100包括箱体10、安装于箱体10内的信号光学系统20与参考光学系统30，箱体10主要用于遮挡外界的环境光，信号光学系统20用于收集信号光并转化成电信号，参考光学系统30提供校准用的标准光源，用于信号光学系统20的漂移校准，以调整检测结果，从而使检测结果更准确。
如图2所示，箱体10包括前置室11、连通前置室11的检测室12及连通信号光学系统20的参考室13，前置室11邻近并连通读数室。
如图2所示，信号光学系统20包括信号光收集器21和光子计数模块22，信号光收集器21和光子计数模块22沿信号光的发射方向依次设置，信号光收集器21设于前置室11，光子计数模块22设于检测室12。测试反应容器内的光信号时，反应容器放置于读数室，反应容器内的反应物发生化学反应向周围发出光信号，其中，靠近信号光收集器21的一面形成发光面，发光面通过信号光收集器21成像于光子计数模块22的感光面上，成像面大小正好覆盖感光面，或者，成像面略小于感光面，让非发光面以外的杂散光无法进入光子计数模块22，从而降低干扰光或背景光干扰。可以理解，信号光收集器21在前置室11的位置可活动调节，即可调节信号光收集器21相对于光子计数模块22的距离，使成像面更好地覆盖感光面，噪声干扰降到最低。
一个实施例中，信号光收集器21为单个凸透镜，凸透镜有聚集光线的作用，可以收集发光面的光线成像投射在光子计数模块22的感光面上，且凸透镜的焦距固定，易于调节成像。此外，单个凸透镜还可进一步精简装置的结构和节约成本。一些实施例中，信号光收集器21还可以是由多个凸透镜组成的透镜组、凸透镜和凹透镜组成的透镜组或者光纤等，亦能获得较好的收集光线并成像于光子计数模块22的感光面的效果。
一个实施例中，光子计数模块22包括检测器23，检测器23可以为工作在计数模式下的端窗型光电倍增管(Photomultiplier tube，缩写PMT)或类似的能将微弱光信号转换成电信号的器件，光电倍增管具有高灵敏度，且响应速度快，可快速地获得测量结果。进一步地，光子计数模块22还可包括光子计数板24，检测器23通过安装座安装在光子计数板24上，光子计数板24上还设有分压电路、高压模块、高增益信号放大器、鉴别器、预分频器、数据处理器等。本领域技术人员可以理解，在其他实施例中，根据电路板的功能划分，光子计数板24可能不止一块，比如可以两块或以上，多块直接通过电线连通。从预分频器的输出连接到用于光子脉冲计数的数据处理器，一些实施例中，预分频器还具有脉冲整形的作用，使脉冲信号更理想。光信号，比如从参考光学系统30、反应容器内反应液产生的发射光信号可以照射到检测器23上。
如图2所示，参考光学系统30包括漫反射腔31、设于漫反射腔31内的参考光源32与光电探测器33、电连接参考光源32与光电探测器33的光电控制板34及连通信号光学系统20与漫反射腔31的光阑35，光电控制板34电连接光子计数模块22，主要用于控制和监控参考光源32的发光强度。漫反射腔31、参考光源32、光电探测器33及光电控制板34均安装于参考室13，参考室13通过光阑35连通信号光学系统20，参考光源32的光线在漫反射腔体31内漫反射后通过光阑35进入信号光学系统20，并投射至光子计数模块22的感光面上，被光子计数模块22检测到。
一个实施例中，漫反射腔31为柱形腔体，柱形腔体中的相邻的内侧壁相 互垂直，使漫反射的光线获得多次折射和反射，增加光程，获得多种不同光程的漫反射光线，这样可以使从漫反射腔31的出射光更均匀和随机，提高光学系统对制造变异的容忍度。
一个实施例中，参考光源32与光电探测器33安装于漫反射腔31中的同一侧，光电探测器33在光电控制板34上的安装高度低于参考光源32，这样可以最大限度减少参考光源32的直射光投射到光电探测器33上，有效提高光电探测器33对参考光源32安装定位差异的容忍度。
一个实施例中，光阑35位于与参考光源32相对的一侧，可获得较长的光程，进一步减弱投射至光阑35的光线的光强。
一个实施例中，为了进一步减弱进入光阑35的参考光，漫反射腔31内设有挡光装置36。比如在漫反射腔31的靠近光阑35的一侧设有挡光装置36，挡光装置36的上方设有通光通道37，参考光源32的部分光线经过漫反射后透过通光通道37进入光阑35，然后投射至光子计数模块22。一个实施例中，挡光装置36为一竖板，用于遮挡参考光源32的直射光线进入光阑35，确保通过光阑35的光都是漫反射光，避免透过光阑35投射至光子计数模块22的光信号过大而损坏光子计数模块22。本领域技术人员可以理解，挡光装置36还可以是其它结构，只要能遮挡参考光源32的直射光线进入光阑36即可。通光通道37可以由挡光装置36与漫反射腔31之间形成，比如挡光装置36侧面和漫反射腔31的腔壁之间形成通光通道37；也可以设置在挡光装置36上，比如在挡光装置36上开设通光通道37，通光通道37可以为通光缝隙或者孔隙。
一个实施例中，漫反射腔31的内壁涂设漫反射涂层，或者设有雾面玻璃，以获得较好的漫反射效果。
参考光源32发射的参考光的光谱基本匹配光子计数模块22探测的信号光的光谱特性，这样可以最大限度地降低由于各种PMT变化的光谱响应而导致的检测差异的可能性。
一个实施例中，参考光源32为绿色光，比如当信号光为反应容器内螺旋 金刚烷及其衍生物发生化学反应产生的发光信号。参考光源32还可以为蓝色光，比如当信号光为反应容器内吖啶酯发生化学反应产生的发光信号。较优地，参考光源32采用LED灯或OLED灯，LED灯和OLED灯易于控制，发光稳定，可作为标准光源使用，且均为面发光，光线比较均匀，漫反射效果较好，避免光线过于集中而大部分光线往同一方向反射，违背了漫反射的初衷。
一个实施例中，为了使结构更简单紧凑，光阑35为设于检测室12的侧壁上的圆形小孔，光阑35连通检测室12与参考室13，参考光源32的光线在漫反射腔31内漫反射后通过光阑35进入信号光学系统20，并投射至光子计数模块22。
一个实施例中，参考光还可以经过信号光收集器21，然后投射至检测器23上，此时，光阑35可以是前置室11的侧壁上的圆形开孔，还可以校正信号光收集器21对信号光采集的影响，光阑35连通前置室与参考室，参考光源32的光线在漫反射腔31内漫反射后通过光阑35进入信号光学系统20，并投射至光子计数模块22。
一个实施例中，光阑35为圆形小孔，圆孔的直径为1～10mm，例如可以为，但不限于1mm、2mm、3.5mm、4mm、6mm、6.5mm、7mm、7.5mm、8mm、8.5mm、9mm、9.5mm或10mm等，可准确控制参考光源32透过光阑35的光信号，同时获得较好的减弱后的参考光投射至光子计数模块22。在其他实施例中，光阑35还可以是任何在光学系统中对光束起着限制作用的实体，如设有透光孔的硬质不透光材料等。光阑35的设置可以保证最终只有很小部分的参考光源32的发射光投射至光子计数模块22，避免超过光子计数模块22的测量范围，甚至导致器件损坏。此外，进出光阑35的参考光都是随机的漫反射光，避免了参考光源32的发射光直接入射到光子计数模块22的检测器上，可以有效减少参考光源32的安装位置变化对校准结果造成的不准确。
通过漫反射腔31和光阑35对参考光源32发射光的改变和衰减，不仅避免了现有技术中扩散板、衰减片、反射镜等各种光学器件的使用，精简了结 构，节约了成本，还可以提高自校准的弱光检测装置100对生产制造过程中的变异的容忍度，即本发明弱光检测装置100对参考光源32的装配精度要求不高。
一个实施例中，光电探测器33为光电二极管(PD，Photodiode)或雪崩光电二极管(APD，Avalanche photodiode)，或者其它类似的能把光信号转换为电信号的器件。光电探测器33用于监测和反馈调节参考光源32的发光强度变化。
参考光学系统30用于对信号光学系统20的校准，通过光电控制板34反馈和控制调节参考光源32的输出光强，参考光源32发出的光线经过在漫反射腔31内的漫反射后，部分光线被光电探测器33检测到，小部分的光线通过光阑35投射至光子计数模块22。根据光阑35和漫反射腔31的结构特性，特定光强的参考光源32的光线通过光阑35的光信号是可以定量的，其通过光阑35的光信号不受外界因素干扰，光电探测器33接收的光信号与透过光阑35的被光子计数模块22接收的光信号成正比，如此，参考光源32被光子计数模块22接收的光信号可同时通过光电探测器33间接准确测量。
例如：设未漂移前，X光强的参考光源，光电探测器33接收的光信号与透过光阑35的被光子计数模块22接收的光信号的比值为S0。当光子计数模块22发生漂移后，通过光电控制板34控制参考光源32的输出光强为X光强，测得光电探测器33接收的光信号与透过光阑35的被光子计数模块22接收的光信号的比值为S1，跟未漂移前的S0作比较，得出校准因子F。
获得校准因子F后，再进行实测反应容器内的反应物，将装有反应物的反应容器置于读数室，测得反应物的光信号Z，根据校准因子F对光子计数模块22进行补偿，即对光信号Z进行校准计算，得出准确的反应容器内的反应物光信号，达到自校准的效果。
需要说明的是，校准和检测时，箱体10与读数室连通实现密闭，外界的光无法透入箱体10内，避免外界光线的干扰。
本发明自校准的弱光检测装置100，信号光学系统20与参考光学系统30 结合，降低了光子计数模块22受各种因素影响而导致测量数据不准确的概率。参考光学系统30采用类积分球结构，输出光是一种漫反射光，而不是直射光，能很好提高参考光源的稳定性，不需要复杂的光学器件，提高校准精度的同时缩减了复杂的结构，提高其稳定性，并且结构简单，体重小，生产制造要求低，保证了稳定性及其性能的基础上大大节约了装置的成本。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。

Claims (20)

  1. 一种自校准的弱光检测装置，包括：
    箱体，所述箱体包括参考室、前置室及连通所述前置室的检测室；
    信号光学系统，所述信号光学系统包括信号光收集器和光子计数模块，所述信号光收集器和光子计数模块沿信号光的发射方向依次设置，所述信号光收集器设于所述前置室，所述光子计数模块设于所述检测室；及
    参考光学系统，所述参考光学系统用于所述信号光学系统的校准，所述参考光学系统包括漫反射腔、设于所述漫反射腔内的参考光源与光电探测器、电连接所述参考光源与光电探测器的光电控制板及连通所述信号光学系统与漫反射腔的光阑，所述光电控制板电连接所述光子计数模块；所述漫反射腔、参考光源、光电探测器及光电控制板安装于所述参考室，所述光阑连通所述信号光学系统与所述参考室，所述参考光源的光线在所述漫反射腔体内漫反射后通过所述光阑进入所述信号光学系统，并投射至所述光子计数模块。
  2. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述漫反射腔内设有挡光装置和通光通道，所述参考光源的光线透过所述通光通道进入所述光阑。
  3. 根据权利要求2所述的自校准的弱光检测装置，其特征在于：所述挡光装置为一竖板。
  4. 根据权利要求2所述的自校准的弱光检测装置，其特征在于：所述通光通道由挡光装置的侧面和漫反射腔的腔壁之间形成。
  5. 根据权利要求2所述的自校准的弱光检测装置，其特征在于：所述通光通道为开设于所述挡光装置上的缝隙或孔隙。
  6. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述光阑为设于所述检测室的侧壁的通孔，所述参考室通过所述光阑连通所述检测室。
  7. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述光 阑为设于所述前置室的侧壁的通孔，所述参考室通过所述光阑连通所述前置室及检测室。
  8. 根据权利要求6或7所述的自校准的弱光检测装置，其特征在于：所述光阑为圆形小孔。
  9. 根据权利要求8所述的自校准的弱光检测装置，其特征在于：所述所述光阑的直径为1～10mm。
  10. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述漫反射腔为柱形腔体。
  11. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述漫反射腔的内壁涂设有漫反射涂层，或者所述漫反射腔的内壁设有雾面玻璃。
  12. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述参考光源与光电探测器安装于所述漫反射腔中的同一侧，所述光阑位于与所述参考光源相对的一侧。
  13. 根据权利要求1或12所述的自校准的弱光检测装置，其特征在于：所述光电探测器于所述光电控制板上的安装高度低于所述参考光源。
  14. 根据权利要求1所述的自校准的弱光检测装置，其特征在于：所述参考光源采用LED灯或OLED灯。
  15. 根据权利要求1或14所述的自校准的弱光检测装置，其特征在于：所述参考光源为绿色光或蓝色光。
  16. 根据权利要求1至3任意一项所述的自校准的弱光检测装置，其特征在于：所述光电探测器为光电二极管或雪崩光电二极管。
  17. 根据权利要求1至3任意一项所述的自校准的弱光检测装置，其特征在于：所述信号光收集器为单个凸透镜。
  18. 根据权利要求1至3任意一项所述的自校准的弱光检测装置，其特征在于：所述光子计数模块包括光子计数板及安装于所述光子计数板的检测器。
  19. 根据权利要求18所述的自校准的弱光检测装置，其特征在于：所述 检测器为光电倍增管。
  20. 权利要求1至19任一项所述的自校准的弱光检测装置的应用，其特征在于：应用于化学发光免疫检测。
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