CN116106523A - Blood analysis device - Google Patents

Blood analysis device Download PDF

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Publication number
CN116106523A
CN116106523A CN202310380525.1A CN202310380525A CN116106523A CN 116106523 A CN116106523 A CN 116106523A CN 202310380525 A CN202310380525 A CN 202310380525A CN 116106523 A CN116106523 A CN 116106523A
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China
Prior art keywords
photoelectric conversion
light beam
wavelength
conversion module
nonlinear
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CN202310380525.1A
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CN116106523B (en
Inventor
郭庆龙
李忠幸
黄勃
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Shenzhen Dymind Biotechnology Co Ltd
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Shenzhen Dymind Biotechnology Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/49Blood
    • G01N33/4915Blood using flow cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N15/1434Electro-optical investigation, e.g. flow cytometers using an analyser being characterised by its optical arrangement
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6402Atomic fluorescence; Laser induced fluorescence

Abstract

The application discloses a blood analysis device, this blood analysis device includes: an optical flow chamber through which a liquid to be measured flows; the light source is used for emitting a coherent light beam towards the optical flow chamber, the coherent light beam irradiates particles in the liquid to be detected flowing in the optical flow chamber, the particles are excited to generate fluorescent light beams, and the particles contain fluorescent dye liquor; the nonlinear photoelectric conversion module is used for carrying out photoelectric conversion on the fluorescent light beams; the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is less than 10 nanometers and/or the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye is greater than 15 nanometers. Based on the mode, the accuracy of the flow detection can be effectively improved.

Description

Blood analysis device
Technical Field
The present application relates to the field of sample detection technology, and in particular, to a blood analysis device.
Background
In the prior art, when a blood analysis device is used for flow detection, a light source is generally used for irradiating a sample containing fluorescent dye liquid flowing in an optical flow chamber, and when a coherent light beam emitted by the light source irradiates the sample, a corresponding fluorescent light beam is generated by excitation, and then the fluorescent light beam is received through a nonlinear photoelectric conversion module, so that a corresponding detection result is obtained, and detection is completed.
The prior art has the defect that the intensity of a fluorescent light beam generated by corresponding excitation due to the absorption of the energy of a coherent light beam by a fluorescent dye in a sample is weak, or the received coherent light beam is easily recognized as the fluorescent light beam by a blood analysis device due to the fact that the wavelength of the coherent light beam is similar to that of the fluorescent light beam, so that the accuracy of flow detection of the blood analysis device based on the fluorescent light beam is low.
Disclosure of Invention
The technical problem that this application mainly solves is how to improve the accuracy of stream detection.
In order to solve the technical problems, the technical scheme adopted by the application is as follows: a blood analysis device, comprising: an optical flow chamber through which a liquid to be measured flows; the light source is used for emitting a coherent light beam towards the optical flow chamber, the coherent light beam irradiates particles in the liquid to be detected flowing in the optical flow chamber, and fluorescent light beams are generated by excitation, wherein the particles contain fluorescent dye liquid; the nonlinear photoelectric conversion module is used for carrying out photoelectric conversion on the fluorescent light beams; wherein the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is less than 10 nanometers and/or the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye is greater than 15 nanometers.
Wherein the difference between the wavelength of the maximum excitation peak of the fluorescent dye and the wavelength of the maximum emission peak of the fluorescent dye is greater than 10 nanometers, and/or the maximum emission peak wavelength of the fluorescent light beam is 650-675 nanometers.
The method comprises the steps that a coherent light beam irradiates particles in liquid to be detected flowing in an optical flow chamber to be excited to generate a fluorescent light beam, and the fluorescent light beam is scattered to form a scattered light beam; the blood analysis device also comprises a light splitting module and a linear photoelectric conversion module; the light splitting module is positioned on a light path of the superposition center of the fluorescent light beam and the scattered light beam, and is used for transmitting the fluorescent light beam and reflecting the scattered light beam; the linear photoelectric conversion module is used for carrying out photoelectric conversion on the scattered light beams; the reflection wave band and the transmission wave band partially coincide, the wavelength of the scattered light beam is smaller than the minimum wavelength of the transmission wave band of the light splitting module, the difference between the wavelength of the scattered light beam and the wavelength of the minimum wavelength of the transmission wave band of the light splitting module is larger than 5 nanometers, and/or the peak wavelength of the fluorescent light beam is larger than the maximum wavelength of the reflection wave band of the light splitting module, and the difference between the peak wavelength of the fluorescent light beam and the wavelength of the maximum wavelength of the reflection wave band of the light splitting module is larger than 5 nanometers.
The light splitting module is a dichroic mirror; the transmittance of the dichroic mirror to the fluorescent light beam is greater than 90%, and/or the reflectance of the dichroic mirror to the scattered light beam is greater than 95%, and/or the wavelength error of the dichroic mirror is between-0.5% and 0.5% of the edge wavelength, and/or the wavelength range of the dichroic mirror is between 250 nanometers and 1000 nanometers, and/or the steepness of the dichroic mirror is less than 4% of the edge wavelength, and/or the transmitted wavefront difference of the dichroic mirror is less than 0.01λ per inch at 632.8 nanometers.
Wherein the peak wavelength of the fluorescent light beam is larger than the peak sensitivity wavelength of the nonlinear photoelectric conversion module, the difference value between the peak wavelength of the fluorescent light beam and the peak sensitivity wavelength of the nonlinear photoelectric conversion module is smaller than 280 nanometers, and/or the light sensitivity of the nonlinear photoelectric conversion device is larger than 7 x 10 4 An ampere/watt, and/or an overvoltage of the nonlinear photoelectric conversion module is greater than 0.5 volt, and/or an overvoltage of the nonlinear photoelectric conversion module is less than 4.5 volt.
Wherein the peak wavelength of the fluorescent light beam is greater than the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module, and the difference between the peak wavelength of the fluorescent light beam and the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module is less than 310 nanometers, and/or the photon detection efficiency of the nonlinear photoelectric conversion module is greater than 10%, and/or the reverse voltage of the nonlinear photoelectric conversion module is greater than the device breakdown voltage and the overvoltage of the nonlinear photoelectric conversion module is greater than 0.5 volt.
Wherein the pixel size of the photosurface of each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module is greater than or equal to 25 micrometers, and/or the total number of all nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module is greater than 500, and/or the photon detection efficiency of each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module is greater than 12%, and/or the total area of the photosurface of the nonlinear photoelectric conversion module is greater than or equal to 36 square millimeters, and/or the ratio of the sum of the areas of the photosurfaces of all nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module to the total area of the photosurface of the nonlinear photoelectric conversion module is not less than 70%.
The sampling pulse period of the nonlinear photoelectric conversion module comprises a rising section and a falling section; the total duration of the rising section is in positive correlation with the total capacitance of the nonlinear photoelectric conversion module and the resistance of the nonlinear photoelectric conversion unit respectively, and/or the total duration of the falling section is in positive correlation with the total capacitance of the nonlinear photoelectric conversion module and the quenching resistance respectively; the total duration of the sampling pulse period of the nonlinear photoelectric conversion module is not more than one tenth of the total duration of the pulse width corresponding to the particles in the single liquid to be tested.
A flat top light module and/or a cylindrical diaphragm module are/is arranged between the optical flow chamber and the nonlinear photoelectric conversion module; the flat top light module is used for converting the fluorescent light beam into a flat top light beam, and the nonlinear photoelectric conversion module is used for performing photoelectric conversion on the fluorescent light beam converted by the flat top light module; the tubular diaphragm module is provided with a tubular cavity, the fluorescent light beam enters from a light inlet of the tubular cavity and exits from a light outlet of the tubular cavity, the inner wall of the tubular cavity is arranged to reflect the fluorescent light beam entering the tubular cavity, and the nonlinear photoelectric conversion module is used for carrying out photoelectric conversion on the fluorescent light beam exiting from the light outlet.
The diameter of the light inlet is larger than or equal to the diameter of the cross section of the fluorescent light beam incident from the light inlet, and the diameter of the cross section of at least one part of the cylindrical inner cavity behind the light inlet is smaller than or equal to the diameter of the cross section of the fluorescent light beam at the corresponding position; each cross section is perpendicular to the central optical path of the fluorescent light beam at a corresponding position.
The beneficial effects of this application lie in: compared with the prior art, in the technical scheme of the application, the blood analysis device comprises an optical flow chamber, a light source and a nonlinear photoelectric conversion module, wherein the light source irradiates the liquid to be detected containing the fluorescent dye liquid flowing in the optical flow chamber, when the coherent light beam irradiates particles containing the fluorescent dye liquid in the liquid to be detected, the liquid can be excited to generate corresponding fluorescent light beams, the nonlinear photoelectric conversion module is used for carrying out photoelectric conversion on the fluorescent light beams to obtain corresponding data for processing analysis, a detection result is obtained, the difference value between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye liquid is smaller than 10 nanometers, the wavelength of the coherent light beam is relatively close to the wavelength of the maximum excitation peak of the fluorescent dye liquid, the energy of the fluorescent dye liquid in the particles is further improved to generate corresponding fluorescent light beam efficiency, namely, the light intensity of the excited fluorescent light beam can be improved under the same coherent light beam, and the difference value between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye liquid is larger than 15 nanometers, so that the accuracy of the coherent light beam and the fluorescence light beam can be distinguished based on the blood analysis device.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic view of a first embodiment of a blood analysis device of the present application;
FIG. 2 is a schematic illustration of waveforms of excitation and emission of the fluorescent dye of the present application;
FIG. 3 is a schematic diagram of waveforms of transmittance and reflectance of a spectroscopic module of the present application;
FIG. 4 is a schematic waveform diagram of the sensitivity versus wavelength relationship of the nonlinear photoelectric conversion module of the present application;
FIG. 5 is a schematic waveform diagram of the sensitivity versus reverse voltage relationship of the nonlinear photoelectric conversion module of the present application;
FIG. 6 is a schematic waveform diagram of photon detection efficiency versus wavelength for a nonlinear photoelectric conversion module of the present application;
FIG. 7 is a schematic view of the structure of a second embodiment of the blood analysis device of the present application;
FIG. 8 is a schematic view of the structure of a third embodiment of the blood analysis device of the present application;
FIG. 9 is a schematic view of a fourth embodiment of a blood analysis device of the present application;
FIG. 10 is a schematic view of the structure of a fifth embodiment of the blood analysis device of the present application;
FIG. 11 is a schematic view of the structure of an embodiment of the nonlinear photoelectric conversion module and the cylindrical aperture module of the present application;
FIG. 12 is a schematic diagram of an embodiment of a cylindrical aperture module and a fluorescent light beam of the present application;
fig. 13 is a schematic diagram of an embodiment of a photosurface and a flare of a nonlinear photoelectric conversion module according to the present application.
Reference numerals: the optical flow chamber 11, the light source 12, the nonlinear photoelectric conversion module 13, the light splitting module 14, the linear photoelectric conversion module 15, the reflection module 16, the optical processing module 17, the flat-top light module 171 and the cylindrical diaphragm module 172.
Detailed Description
The present application is described in further detail below with reference to the drawings and examples. It is specifically noted that the following examples are only for illustration of the present application, but do not limit the scope of the present application. Likewise, the following embodiments are only some, but not all, of the embodiments of the present application, and all other embodiments obtained by one of ordinary skill in the art without making any inventive effort are within the scope of the present application.
Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present application. The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Those of skill in the art will explicitly and implicitly appreciate that the embodiments described herein may be combined with other embodiments.
In the description of the present application, it is to be understood that the terms "mounted," "configured," "connected," and "connected" are to be interpreted broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected, unless explicitly stated and defined otherwise; the connection can be mechanical connection or electric connection; may be directly connected or may be connected via an intermediate medium. It will be apparent to those skilled in the art that the foregoing is in the specific sense of this application.
The present application proposes a blood analysis device, referring to fig. 1, fig. 1 is a schematic structural view of a first embodiment of the blood analysis device of the present application, and as shown in fig. 1, the blood analysis device includes an optical flow chamber 11, a light source 12, and a nonlinear photoelectric conversion module 13.
The liquid to be measured, which contains the particles to be detected, is passed through an optical flow cell 11, wherein the particles contain a fluorescent dye.
Wherein the optical flow cell 11 is configured for the particles to flow therethrough, and the light source 12 is configured to emit a beam of coherent light towards the optical flow cell 11, such that the beam of coherent light impinges on the particles flowing in the optical flow cell 11, and excites to generate a corresponding fluorescent light beam. The particles in the blood sample flow through the optical flow cell 11, and the particles may be cells to be measured to which a fluorescent dye is attached, or may be other types of particles that can be excited by a coherent light beam to generate a fluorescent beam, and are not limited herein. The coherent light beam impinges on the particle, and the fluorescent dye in the particle can be excited by photons in the coherent light beam to generate a corresponding fluorescent light beam that diverges from the particle in any direction. The particles may be, in particular, erythrocytes or platelets or other particles to be subjected to a sample test, without limitation.
The nonlinear photoelectric conversion module 13, the nonlinear photoelectric conversion module 13 is used for carrying out photoelectric conversion on the fluorescent light beam.
The nonlinear photoelectric conversion module 13 may be a detection module based on a single photon avalanche diode array. The nonlinear photoelectric conversion module 13 may specifically be a detection module formed by a single photon avalanche diode array in nonlinear Mode (Geiger-Mode).
First, the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is less than 10 nanometers.
It should be noted that, referring to fig. 2, fig. 2 is a schematic diagram of excitation and emission waveforms of the fluorescent dye according to the present application, and as shown in fig. 2, in an excitation waveform a of the fluorescent dye, the stronger the relative energy represented by the vertical axis, the higher the absorption efficiency of the fluorescent dye for absorbing the light beam with the corresponding wavelength.
When the relative energy corresponding to the vertical axis is strongest, the corresponding wavelength C is the wavelength of the maximum excitation peak of the fluorescent dye, that is, the absorption efficiency of the fluorescent dye on the coherent light beam with the wavelength C is highest compared with that of the coherent light beams with other wavelengths.
As shown in fig. 2, in a certain wavelength range, the smaller the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye, the higher the absorption efficiency of the fluorescent dye for converting the absorption of the coherent light beam into the fluorescent beam, and the higher the absorption efficiency, the stronger the light intensity of the fluorescent beam generated by the fluorescent dye excited by the same coherent light beam irradiation.
The difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye may be less than 10 nm, may be less than 8 nm, may be less than 6 nm, may be other values, wherein the absorption efficiency of the fluorescent dye when the difference is less than 6 nm is greater than the absorption efficiency of the fluorescent dye when the difference is less than 8 nm, and the absorption efficiency of the fluorescent dye when the difference is less than 8 nm is greater than the absorption efficiency of the fluorescent dye when the difference is less than 10 nm.
Based on the mode, the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is smaller than 10 nanometers, so that the absorption efficiency of the fluorescent dye can reach the requirement standard, the light intensity of the excited fluorescent light beam is improved under the same light intensity of the coherent light beam, and the accuracy of flow detection of the blood analysis device based on the fluorescent light beam is improved.
Second, the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye is greater than 15 nanometers.
In the emission waveform B of the fluorescent dye, as shown in fig. 2, the stronger the relative energy represented by the vertical axis, the higher the intensity of the fluorescent beam of the corresponding wavelength among all the fluorescent beams excited and emitted by the fluorescent dye by irradiation.
When the relative energy corresponding to the vertical axis is strongest, the corresponding wavelength D is the wavelength of the maximum emission peak of the fluorescent dye, namely, the fluorescent dye is irradiated to excite all the fluorescent light beams with the wavelength D, and the light intensity of the fluorescent light beams with the wavelength D is highest.
As shown in fig. 2, in a certain wavelength range, the greater the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye solution, the greater the degree of distinction between the fluorescent light beam and the coherent light beam due to the highest light intensity of the part of the fluorescent light beam having the wavelength equal to the wavelength of the maximum emission peak, the greater the degree of distinction represents that the nonlinear photoelectric conversion module 13 erroneously recognizes the received coherent light beam as the fluorescent light beam, so that the probability of causing a detection result error is lower, and the accuracy of the flow detection is further improved.
The difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye may be greater than 15 nm, may be greater than 20 nm, may be greater than 25 nm, may be other values, wherein the degree of distinction when the difference is greater than 25 nm is greater than the degree of distinction when the difference is greater than 20 nm, and the degree of distinction when the difference is greater than 20 nm is greater than the degree of distinction when the difference is greater than 15 nm.
Based on the above manner, by making the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye solution be greater than 15 nm, the degree of distinction between the fluorescent light beam and the coherent light beam can be improved, so that the possibility that the nonlinear photoelectric conversion module 13 erroneously recognizes the received coherent light beam as a fluorescent light beam is reduced, and the accuracy of the flow detection of the blood analysis device based on the fluorescent light beam is improved.
In addition, the wavelength of the coherent light beam may be less than or equal to or greater than the wavelength of the maximum excitation peak of the fluorescent dye, which is not limited herein.
Compared with the prior art, in the technical scheme of the application, the blood analysis device comprises the optical flow chamber 11, the light source and the nonlinear photoelectric conversion module 13, the light source irradiates the liquid to be detected containing the fluorescent dye flowing in the optical flow chamber 11, when the coherent light beam irradiates the particles containing the fluorescent dye in the liquid to be detected, the corresponding fluorescent light beam can be generated by excitation, the nonlinear photoelectric conversion module 13 is used for carrying out photoelectric conversion on the fluorescent light beam to obtain corresponding data for processing analysis, a detection result is obtained, the difference value between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is smaller than 10 nanometers, the wavelength of the coherent light beam is relatively close to the wavelength of the maximum excitation peak of the fluorescent dye, the energy of the fluorescent dye in the particles absorbed by the fluorescent dye is further improved to generate the corresponding fluorescent light beam efficiency, namely, the light intensity of the fluorescent light beam generated by excitation can be improved under the same light intensity of the coherent light beam, and the difference value between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye is larger than 15 nanometers, so that the accuracy of the fluorescence light beam can be distinguished from the device based on the fluorescence light beam analysis can be greatly improved, and the accuracy of the blood analysis device is improved.
In one embodiment, the difference between the wavelength of the maximum excitation peak of the fluorescent dye and the wavelength of the maximum emission peak of the fluorescent dye is greater than 10 nanometers,
and/or the maximum emission peak wavelength of the fluorescent light beam is 650-675 nanometers.
Specifically, based on the above manner, by selecting a proper type of fluorescent dye, the difference between the wavelength of the maximum excitation peak of the fluorescent dye and the wavelength of the maximum emission peak of the fluorescent dye is greater than 10 nanometers, so that the situation that the wavelength of the coherent light used for exciting and generating fluorescence is relatively close to the main wavelength of the fluorescent light beam due to the fact that the difference between the wavelength of the maximum excitation peak of the fluorescent dye and the wavelength of the maximum emission peak is too small is avoided, and the possibility that the nonlinear photoelectric conversion module 13 erroneously recognizes the received coherent light beam as the fluorescent light beam is reduced, so that the accuracy of flow detection of the blood analysis device based on the fluorescent light beam is improved.
In addition, by selecting a proper type of fluorescent dye, the maximum emission peak wavelength of the fluorescent light beam is 650-675 nanometers, when the maximum emission peak wavelength of the fluorescent light beam is in the range, the probability that the nonlinear photoelectric conversion module 13 receives photons of the fluorescent light beam to generate corresponding electron hole pairs is higher, that is, the probability that the nonlinear photoelectric conversion module 13 successfully generates corresponding carriers when receiving photons of the fluorescent light beam with the wavelength of 650-675 nanometers is higher, which leads the photon detection efficiency of the nonlinear photoelectric conversion module 13 when receiving the fluorescent light beam with the wavelength of 650-675 nanometers to be higher, and further improves the intensity of an electric signal generated by the nonlinear photoelectric conversion module 13 on the premise of the same fluorescent light beam, and further improves the reliability of the blood analysis device.
In one embodiment, a beam of coherent light is directed onto particles in a fluid under test flowing in the optical flow cell 11 to excite and generate a beam of fluorescent light and scatter the beam of fluorescent light to form a scattered beam.
As shown in fig. 1, the blood analysis device further includes a spectroscopic module 14 and a linear photoelectric conversion module 15.
The light splitting module 14 is located on the light path of the coincidence center of the fluorescent light beam and the scattered light beam, and the light splitting module 14 is used for transmitting the fluorescent light beam and reflecting the scattered light beam.
The linear photoelectric conversion module 15 is used for photoelectric conversion of the scattered light beam.
The reflection band partially coincides with the transmission band.
The wavelength of the scattered light beam is less than the minimum wavelength of the transmission band of the spectroscopic module 14, and the difference between the wavelength of the scattered light beam and the wavelength of the minimum wavelength of the transmission band of the spectroscopic module 14 is greater than 5 nanometers,
and/or, the peak wavelength of the fluorescent light beam is greater than the maximum wavelength of the reflection band of the spectroscopic module 14, and the difference between the peak wavelength of the fluorescent light beam and the wavelength of the maximum wavelength of the reflection band of the spectroscopic module 14 is greater than 5 nanometers.
Specifically, referring to fig. 3, fig. 3 is a schematic diagram of waveforms of transmittance and reflectivity of the spectroscopic module 14 of the present application, as shown in fig. 3, in a transmittance curve E, a wavelength band with a wavelength greater than G is the above-mentioned transmission wavelength band, the spectroscopic module 14 can perform transmission processing on a light beam (for example, a fluorescent light beam) in the transmission wavelength band, and in a reflectivity curve F, a wavelength band with a wavelength less than H is the above-mentioned reflection wavelength band, the spectroscopic module 14 can perform reflection processing on a light beam (for example, a coherent light beam) in the reflection wavelength band.
As shown in fig. 3, the reflection band partially coincides with the transmission band, that is, the spectroscopic module 14 reflects and partially transmits a portion of the light beam in the band having a wavelength greater than G and less than H.
By making the wavelength of the scattered light beam smaller than the minimum wavelength G of the transmission band of the beam splitting module 14 and the difference between the wavelength of the scattered light beam and the wavelength G larger than 5 nm, the scattered light beam formed by scattering the coherent light beam can be totally reflected as much as possible without being transmitted when passing through the beam splitting module 14. Similarly, by making the peak wavelength of the fluorescent light beam larger than the maximum wavelength H of the reflection band of the spectroscopic module 14 and making the difference between the peak wavelength of the fluorescent light beam and the wavelength H larger than 5 nm, the fluorescent light beam can be transmitted as completely as possible without being reflected when passing through the spectroscopic module 14.
Based on the above manner, the fluorescent light beam can be received by the nonlinear photoelectric conversion module 13 as much as possible, and/or the scattered light beam can be received by the linear photoelectric conversion module 15 as much as possible, thereby improving the light energy utilization rate and the accuracy of the stream detection.
Specifically, the blood analysis device may further include a reflection module 16, where the reflection module 16 is configured to reflect the transmitted fluorescent light beam, so that a direction of the reflected fluorescent light beam is parallel to a direction of the coherent light beam.
Optionally, the light splitting module 14 is a dichroic mirror.
The transmittance of the dichroic mirror for the fluorescent light beam is greater than 90%,
and/or the dichroic mirror has a reflectivity of more than 95% for the scattered light beam,
and/or the wavelength error of the dichroic mirror is between-0.5% -0.5% of the edge wavelength,
and/or the wavelength range of the dichroic mirror is between 250 nm and 1000 nm,
and/or, the steepness of the dichroic mirror is less than 4% of the edge wavelength,
and/or the transmitted wavefront difference of the dichroic mirror is less than 0.01λ per inch at 632.8 nanometers.
Specifically, the transmittance of the dichroic mirror to the fluorescent light beam is more than 90%, and the utilization ratio of the fluorescent light beam by the blood analysis device can be improved.
The reflectance of the dichroic mirror to the scattered light beam is more than 95%, and the utilization ratio of the scattered light beam by the blood analysis device can be improved.
In the dichroic mirror, the wavelength error is < ±0.5% Edge wavelength, and the wavelength error specifically may be a spectroscopic wavelength error value of the dichroic mirror, so that the possibility that the dichroic mirror mistakenly reflects the fluorescent light beam or mistakenly transmits the scattered light beam can be reduced by making the wavelength error between-0.5% -0.5% of Edge wavelength, thereby improving the accuracy of the blood analysis device in performing flow detection.
The wavelength range is 250-1000 nanometers, the dichroic mirror can perform corresponding transmission or reflection treatment on the light beams in the wavelength range according to the corresponding wavelengths, and the application range of the dichroic mirror is improved.
The steepness is less than 4% Edge wavelength, and the steepness may specifically refer to the steepness of the waveform between the wavelength G and the wavelength H as shown in fig. 3, and when the steepness is less than 4% Edge wavelength, the wavelength width of the light beam that can be reflected by the dichroic mirror and transmitted can be reduced, so that the wavelength width of the light beam that can be completely reflected by the dichroic mirror or completely transmitted can be further improved, and the possibility that the fluorescent light beam is mistakenly reflected or scattered can be reduced.
Transmitted wavefront difference (RMS): * And preferably 0.01 lambda per inch @ 632.8 nm, the dichroic mirror based on the transmitted wavefront difference can be used for carrying out light splitting, so that the central optical paths of fluorescent light beams are kept consistent before and after transmission, negative influence of the dichroic mirror on the transmitted fluorescent light beams is avoided, and the accuracy of flow detection of the blood analysis device is improved.
Based on the above manner, the possibility that the wavelength of the light beam reflected and transmitted by the dichroic mirror does not meet the requirement can be reduced, and the accuracy of the flow detection of the blood analysis device can be further improved.
In one embodiment, the difference between the peak wavelength of the fluorescent light beam and the peak sensitivity wavelength of the nonlinear photoelectric conversion module 13 is less than 280 nanometers, and/or the overvoltage of the nonlinear photoelectric conversion module 13 is greater than 0.5 volt.
Specifically, referring to fig. 4, fig. 4 is a waveform schematic diagram of the relationship between the sensitivity and the wavelength of the nonlinear photoelectric conversion module 13 in the present application, as shown in fig. 4, I is the wavelength when the sensitivity of the nonlinear photoelectric conversion module 13 is the highest, that is, the peak sensitivity wavelength.
By making the difference between the peak wavelength of the fluorescent light beam and the peak sensitivity wavelength of the nonlinear photoelectric conversion module 13 smaller than 280 nanometers, the light intensity of the light beam received by the nonlinear photoelectric conversion module 13 can be improved, and the accuracy of the blood analysis device can be further improved.
The sensitivity of the nonlinear photoelectric conversion module 13 is the ratio of the light output current in the nonlinear photoelectric conversion module 13 to the light incident on the nonlinear photoelectric conversion module 13, the sensitivity is used to represent the light detection sensitivity of the nonlinear photoelectric conversion module 13, the higher the light detection sensitivity is, the stronger the signal generated by the nonlinear photoelectric conversion module 13 receiving the light beam with the same light intensity is, the gain value of the nonlinear photoelectric conversion module 13 is in direct proportion, and the gain value of the nonlinear photoelectric conversion module 13 is in direct proportion to the reverse voltage thereof, therefore, referring to fig. 5, fig. 5 is a waveform schematic diagram of the relation between the sensitivity of the nonlinear photoelectric conversion module 13 and the reverse voltage, as shown in fig. 5, the sensitivity of the nonlinear photoelectric conversion module 13 increases with the increase of the reverse voltage.
By making the light sensitivity of the nonlinear photoelectric conversion module 13 greater than 7×104 a/watt, the photoelectric conversion capability of the nonlinear photoelectric conversion module 13 can be enhanced, and thus, on the premise of the same fluorescent light beam, the intensity of the electric signal generated by the nonlinear photoelectric conversion module 13 is improved, and further, the reliability of the blood analysis device is improved.
By making the overvoltage of the nonlinear photoelectric conversion module 13 greater than 0.5 v, the sensitivity of the nonlinear photoelectric conversion module 13 can be improved, and the intensity of the electrical signal generated by the nonlinear photoelectric conversion module 13 can be improved on the premise of the same fluorescent light beam, so that the reliability of the blood analysis device can be improved.
In one embodiment, the overvoltage of the nonlinear photoelectric conversion module 13 is less than 4.5 volts.
Specifically, the nonlinear photoelectric conversion module 13 includes a plurality of photosensitive cells, crosstalk is easily generated between adjacent photosensitive cells, the crosstalk rate is 5-10%, the crosstalk will generate noise with corresponding voltage amplitude, and the crosstalk and the overvoltage of the nonlinear photoelectric conversion module 13 are in positive correlation, wherein the overvoltage is a difference between a reverse bias voltage and a breakdown voltage applied to the nonlinear photoelectric conversion module 13.
The overvoltage may be less than 4.5 volts, may be less than 3 volts, may be less than 1.5 volts, or may be less than other voltage values, without limitation.
Based on the mode, noise influenced by overvoltage can be reduced below a required level, and the accuracy of flow detection of the blood analyzer is improved.
In one embodiment, the peak wavelength of the fluorescent light beam is greater than the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module 13, the difference between the peak wavelength of the fluorescent light beam and the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module 13 is less than 310 nanometers,
and/or the photon detection efficiency of the nonlinear photoelectric conversion module 13 is greater than 10%,
and/or, the reverse voltage of the nonlinear photoelectric conversion module 13 is greater than the device breakdown voltage and the overvoltage of the nonlinear photoelectric conversion module 13 is greater than 0.5 volt,
specifically, referring to fig. 6, fig. 6 is a waveform schematic diagram of a relationship between photon detection efficiency and wavelength of the nonlinear photoelectric conversion module 13 in the present application, as shown in fig. 6, J is a wavelength when the photon detection efficiency of the nonlinear photoelectric conversion module 13 is highest, that is, a peak wavelength of the photon detection efficiency.
The photon detection efficiency may specifically refer to a ratio between the number of photons detected by the nonlinear photoelectric conversion module 13 and the number of photons received, which is used to characterize the photoelectric conversion capability of the device, and the higher the photon detection efficiency is, the stronger the photoelectric conversion capability is, that is, since the light-sensitive surface of the nonlinear photoelectric conversion module 13 easily reflects a certain light, the photons reaching the light-sensitive surface are not necessarily able to enter the nonlinear photoelectric conversion module 13 and generate corresponding electrical signals, so that the photon detection efficiency is generally less than 100%, where the photon detection efficiency is respectively in positive correlation with the filling factor, the quantum efficiency and the avalanche probability, and the relation formula is as follows:
PDE=Fg*QE*Pa(1)
In the formula (1), PDE is photon detection efficiency, fg is a filling factor, QE is quantum efficiency, and Pa is avalanche probability.
The photon detection efficiency quantifies the ability of the nonlinear photoelectric conversion module 13 to detect photons, i.e., the ratio of the number of photons detected to the total number of photons of the nonlinear photoelectric conversion module 13 can be characterized, and the calculated function of the photon detection efficiency can also be a function of the overvoltage in the nonlinear photoelectric conversion module 13 and the wavelength of the incident light beam (e.g., fluorescent light beam). In addition, the photon detection efficiency may also be related to the effective transmittance, which is used to describe the proportion of the number of photons reaching the photosurface of the nonlinear photoelectric conversion module 13 that are not reflected to the total number of photons reaching the photosurface.
The filling factor and the effective detection area ratio are in positive correlation, the effective detection area is the ratio of the area capable of being used for detecting photons in the total area of the photosurfaces of the nonlinear photoelectric conversion module 13, the nonlinear photoelectric conversion module 13 is generally provided with a plurality of nonlinear photoelectric conversion units, the photosurfaces of the whole nonlinear photoelectric conversion module 13 can be obtained by arranging the photosurfaces of the nonlinear photoelectric conversion units, but a certain gap is usually reserved between the adjacent nonlinear photoelectric conversion units, and photons can not cause avalanche phenomenon when striking the gap, namely photons striking the gap cannot be effectively detected, so that the effective detection area ratio of the nonlinear photoelectric conversion module 13 can be represented by the ratio of the total area of the photosurfaces of the nonlinear photoelectric conversion units in the total area of the photosurfaces of the nonlinear photoelectric conversion module 13.
The larger the effective detection area ratio is, the smaller the total area of the area where the gap between the adjacent nonlinear photoelectric conversion units is located is, and the larger the filling factor is, the higher the photon detection efficiency is.
The smaller the effective detection area ratio is, the larger the total area of the area where the gap between the adjacent nonlinear photoelectric conversion units is, and the smaller the filling factor is, the lower the photon detection efficiency is.
In general, when the total area of the photosurfaces of the nonlinear photoelectric conversion modules 13 is constant, the smaller the photosurface area of the individual nonlinear photoelectric conversion units in the nonlinear photoelectric conversion modules 13 is, the larger the number of gaps is, the smaller the effective detection area ratio is, and the lower the photon detection efficiency is.
The quantum efficiency is the probability of converting photons into electron-hole pairs after entering the photosurface, namely the probability of generating carriers, and is related to the peak wavelength of the fluorescent light beam entering the photosurface.
The avalanche probability is the probability of generating a carrier avalanche multiplication phenomenon in the nonlinear photoelectric conversion module 13, and the avalanche probability respectively has a positive correlation with the overvoltage and the reverse voltage, that is, the larger the overvoltage or the reverse voltage is, the larger the avalanche probability is, and the larger the photon detection efficiency is.
Based on any one of the above modes, the photon detection efficiency of the nonlinear photoelectric conversion module 13 can be improved by influencing at least one of the filling factor, the quantum efficiency and the avalanche probability, so that the intensity of the electric signal generated by the nonlinear photoelectric conversion module 13 can be improved on the premise of the same fluorescent light beam, and the reliability of the blood analysis device can be further improved.
In one embodiment, the pixel size of the photosurface of each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module 13 is 25 microns or more,
and/or, the total number of all nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is greater than 500,
and/or, the photon detection efficiency of each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module 13 is greater than 12%,
and/or, the total area of the photosurfaces of the nonlinear photoelectric conversion module 13 is 36 square millimeters or more,
and/or, the sum of the areas of the photosurfaces of all the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is not less than 70% of the total area of the photosurfaces of the nonlinear photoelectric conversion module 13.
Specifically, when the pixel size of the photosurface of each of the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is equal to 25 micrometers, the photon detection efficiency is 10%, when the pixel size of the photosurface of each of the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is equal to 50 micrometers, the photon detection efficiency is 15%, and when the pixel size of the photosurface of each of the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is equal to 75 micrometers, the photon detection efficiency is 12%, that is, when the total area of the photosurfaces of the nonlinear photoelectric conversion modules 13 is constant, the greater the pixel size of the photosurface of each of the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is, the higher the photoelectron detection efficiency is, and the greater the total number of all the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 is.
In addition, the ratio of the effective detection area to the total MPPC area can be increased by making the sum of the areas of the photosurfaces of all the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 be not less than 70%, so that the size or the number of gaps existing between adjacent nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 can be reduced, the effective detection area ratio can be increased, and the photon detection efficiency can be further improved.
Based on the above manner, the size or the number of gaps existing between adjacent nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module 13 mentioned in the foregoing embodiment can be reduced, so as to achieve the purpose of improving the effective detection area ratio, and improve the photoelectric detection efficiency of the nonlinear photoelectric conversion module 13, so as to improve the intensity of an electrical signal generated by the nonlinear photoelectric conversion module 13 based on a fluorescent light beam with the same light intensity, and further improve the accuracy of flow detection of the blood analysis device.
When the total area of the light-sensitive surface of the nonlinear photoelectric conversion module 13 is 36 square millimeters or more, the entire part of the light spot formed by the fluorescent light beam can be received as much as possible, thereby improving the utilization ratio of the fluorescent light spot.
Alternatively, the shape of the light-sensitive surface of the nonlinear photoelectric conversion module 13 may be a square with a side length of more than 6 mm, or may be other shapes satisfying the conditions, which is not limited herein.
Based on the above manner, the nonlinear photoelectric conversion module 13 can have a photosensitive surface with a large enough area to receive the light spot with a large area formed by the fluorescent light beam as completely as possible, thereby improving the accuracy of flow detection of the blood analysis device.
In an embodiment, in the case where the ratio of the spot area of the fluorescent light beam formed on the light-sensing surface of the nonlinear photoelectric conversion module 13 to the area of the light-sensing surface of the nonlinear photoelectric conversion module 13 is greater than 70%, specifically, as shown in fig. 13, a circle formed by broken lines represents the spot profile.
As shown in fig. 13 (a), in the case where the fluorescent light beam forms a spot only on the light-sensing surface of the nonlinear photoelectric conversion module 13, the ratio of the spot area to the area of the light-sensing surface may be pi/4 at the maximum, about 78.54%. The ratio of the spot area to the area of the photosensitive surface may be other value of 70% or more, such as 71% or 75%, and is not limited herein.
As shown in fig. 13, if the fluorescent light beam forms not only a flare on the photosurface of the nonlinear photoelectric conversion module 13 but also a part of the flare can be located outside the photosurface, then, in the case where the area of a hatched portion where the flare is located outside the photosurface as shown in (B) of fig. 13 is not larger than the area where the flare does not exist on the photosurface, by reasonably setting the size and position of the flare on the photosurface, the ratio of the flare area formed by the fluorescent light beam on the photosurface of the nonlinear photoelectric conversion module 13 to the area of the photosurface of the nonlinear photoelectric conversion module 13 can be made larger than pi/4. In this way, the light-sensitive surface utilization rate of the nonlinear photoelectric conversion module 13 can be improved while ensuring a sufficiently high light spot utilization rate as much as possible.
Based on the above mode, the proportion of the light spot area to the light sensitive surface area can be enlarged, so that the energy distribution of the light spots on the light sensitive surface is homogenized as much as possible, the accuracy of flow detection is improved, meanwhile, the utilization rate of the light sensitive surface of the nonlinear photoelectric conversion module 13 can be improved, and the waste of resources is reduced.
In one embodiment, the sampling pulse period of the nonlinear photoelectric conversion module 13 includes a rising segment and a falling segment.
The total duration of the rising section is in positive correlation with the total capacitance of the nonlinear photoelectric conversion module 13 and the resistance of the nonlinear photoelectric conversion unit respectively,
and/or, the total duration of the falling section is in positive correlation with the total capacitance and the quenching resistance of the nonlinear photoelectric conversion module 13 respectively.
The total duration of the sampling pulse period of the nonlinear photoelectric conversion module 13 is not more than one tenth of the total duration of the pulse width corresponding to the particles in the single liquid to be measured.
Specifically, the nonlinear photoelectric conversion module 13 may be a detection module based on a single photon avalanche diode array, that is, each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module 13 is a single photon avalanche diode, and the resistance of the nonlinear photoelectric conversion unit may be specifically the resistance of the single photon avalanche diode.
In the sampling pulse period of the nonlinear photoelectric conversion module 13, the total time length of the rising section is in positive correlation with the total capacitance of the nonlinear photoelectric conversion module 13 and the resistance of the nonlinear photoelectric conversion unit respectively, and the total time length of the falling section is in positive correlation with the total capacitance of the nonlinear photoelectric conversion module 13 and the quenching resistance respectively.
By making the total duration of the sampling pulse period of the nonlinear photoelectric conversion module 13 not longer than one tenth of the total duration of the pulse width corresponding to the particles in the single liquid to be detected, the possibility that the loss detection result of the corresponding particles cannot be accurately obtained due to the too low sampling frequency in the pulse width of the single particles detected by the flow detection can be reduced, and the accuracy of the loss detection of the blood analysis device is improved.
For example, where the pulse width of a single particle is 600 nanoseconds, the total duration of the sampling pulse period is no greater than 60 nanoseconds.
In an embodiment, a flat top light module 171 and/or a cylindrical diaphragm module 172 is further disposed between the optical flow chamber 11 and the nonlinear photoelectric conversion module 13.
The flat top light module 171 is used for converting the fluorescent light beam into a flat top light beam, and the nonlinear photoelectric conversion module 13 is used for performing photoelectric conversion on the fluorescent light beam converted by the flat top light module 171.
The cylindrical diaphragm module 172 has a cylindrical cavity, the fluorescent light beam enters from the light inlet of the cylindrical cavity and exits from the light outlet of the cylindrical cavity, the inner wall of the cylindrical cavity is configured to reflect the fluorescent light beam entering the cylindrical cavity, and the nonlinear photoelectric conversion module 13 is configured to photoelectrically convert the fluorescent light beam passing through the cylindrical diaphragm module 172.
Specifically, in the first example, as shown in fig. 7, only the plano-roof light module 171 is provided between the optical flow cell 11 and the nonlinear photoelectric conversion module 13.
The reflected fluorescent light Beam can be correspondingly converted based on the flat Top light module 171 to form a corresponding flat Top light Beam to the light sensitive surface of the nonlinear photoelectric conversion module 13, wherein the flat Top light module 171 is one of the most widely used Diffraction Optical Elements (DOE), and the english name is Beam shape, which has the functions of obtaining a flat Top light spot (Top-hat) with uniform energy distribution, steep boundary and a specific shape. The plano-roof light module 171 is also a light field mapping optical system, and converts an input light beam having a non-uniform light intensity distribution into a flat-top light beam having a relatively uniform light intensity distribution. By adopting the design of the optical field mapping optical system, the light intensity distribution of the converted light beam is relatively flat and uniform, so that the energy distribution uniformity of the light spot formed by the fluorescent light beam on the nonlinear photoelectric conversion module 13 is improved, and the accuracy of flow detection is further improved.
In the second example, as shown in fig. 8, only the cylindrical diaphragm module 172 is provided between the optical flow chamber 11 and the nonlinear photoelectric conversion module 13.
Since the inner wall of the cylindrical cavity of the cylindrical diaphragm module 172 is configured to reflect the fluorescent light beam entering the cylindrical cavity, the inner wall may have a reflective coating, or the material of the cylindrical cavity may reflect the fluorescent light beam, or may have the capability of reflecting the fluorescent light beam in other manners. Since the light intensity distribution of the fluorescent light beam is generally strong in the middle and weak in the periphery, and after the fluorescence of the shadow portion in fig. 12 (a) is reflected and superimposed on the shadow portion in fig. 12 (B), the fluorescent light intensity of the shadow portion in fig. 12 (B) is increased more than that in the case where the reflection is not superimposed, so that the fluorescence of the shadow portion in fig. 12 (B) is correspondingly enhanced without the change in the fluorescent light intensity of the middle portion. That is, the spot energy distribution formed by the fluorescent light beam passing through the cylindrical aperture module 172 can be made uniform. Compared with the fluorescent light beam before passing through the cylindrical inner cavity, the energy distribution of the formed light spots is more uniform, or stray light cannot enter the nonlinear photoelectric conversion module 13, so that the accuracy of photoelectric data received by the nonlinear photoelectric conversion module 13 is improved, and the accuracy of flow detection is improved.
In the third example, as shown in fig. 9, a plano-roof light module 171 and a cylindrical diaphragm module 172 are provided simultaneously between the optical flow chamber 11 and the nonlinear photoelectric conversion module 13.
The flat top light module 171 and the cylindrical diaphragm module 172 can process the passing light beam, so as to improve the uniformity of energy distribution of the light spot formed by the fluorescent light beam on the nonlinear photoelectric conversion module 13, and improve the accuracy of flow detection.
Alternatively, when the cylindrical diaphragm module 172 is provided between the optical flow cell 11 and the nonlinear photoelectric conversion module 13. The diameter of the light inlet of the cylindrical inner cavity is larger than or equal to the diameter of the cross section of the fluorescent light beam incident from the light inlet, and the diameter of the cross section of at least one part of the cylindrical inner cavity behind the light inlet is smaller than or equal to the diameter of the cross section of the fluorescent light beam at the corresponding position. Each cross section is perpendicular to the central optical path of the fluorescent light beam at a corresponding position. Because the light intensity distribution of the fluorescent light beam is generally strong in the middle and weak in the periphery, the diameter of the cross section of at least one part of the cylindrical inner cavity behind the light inlet is smaller than or equal to that of the cross section of the fluorescent light beam at the corresponding position, the light received at the part is reflected and transmitted to the middle part of the periphery, the fluorescent light intensity at the middle part of the periphery is enhanced, the fluorescent light intensity at the middle part is unchanged, and the light spot energy distribution is further homogenized.
Taking fig. 11 and 12 as an example, the fluorescent light beam propagates to the periphery according to the emission direction before being reflected by the inner wall of the cylindrical cavity to form a spot portion of the shadow portion in fig. 12 (a), since the diameter of the cross section of the fluorescent light beam at P2 of the cylindrical diaphragm module 172 shown in fig. 11 is equal to or smaller than the diameter of the cross section of the fluorescent light beam at P2, the fluorescent light originally propagating to the periphery (such as the fluorescent light of the shadow portion in fig. 12 (a)) is superimposed to the middle of the periphery (such as the shadow portion in fig. 12 (B)) after reflection, and the light intensity of the fluorescent light of the periphery (such as the shadow portion in fig. 12 (B)) is increased compared with the case without reflection, so that the fluorescent light intensity of the shadow portion in fig. 12 (B) is correspondingly enhanced without change of the fluorescent light intensity of the middle portion. That is, the spot energy distribution formed by the fluorescent light beam passing through the cylindrical aperture module 172 can be made uniform.
In the fourth example, as shown in fig. 10, an optical processing module 17 is provided between the optical flow chamber 11 and the nonlinear photoelectric conversion module 13, and the optical processing module 17 includes a flat roof light module 171 and a cylindrical diaphragm module 172.
The flat roof light module 171 and the tubular aperture module 172 may be an integrated structure, may be a spliced structure, may be two parts in the same module, or may be the same module, and are not limited herein.
Specifically, as shown in fig. 8 or 10, when the cylindrical aperture module 172 is disposed between the optical flow chamber 11 and the nonlinear photoelectric conversion module 13, as shown in fig. 11, the diameter of the cylindrical aperture module 172 at the light entrance P1 needs to be equal to or larger than the cross-sectional diameter of the fluorescent light beam incident from the light entrance P1, so that all the fluorescent light beams can be injected into the cylindrical aperture module 172 as much as possible, and the possibility of blocking the propagation of the fluorescent light beams is reduced.
Further, the diameter of the cylindrical diaphragm module 172 at the light entrance P1 may be equal to the cross-sectional diameter of the fluorescent light beam incident from the light entrance P1, thereby minimizing the adverse effect of the stray light on the nonlinear photoelectric conversion module 13.
As shown in fig. 11, the cylindrical diaphragm module 172 further has at least one point P2 having a diameter equal to or smaller than the diameter of the cross section of the fluorescent light beam at the point, and as shown in fig. 12, the fluorescent light beam in the shadow portion in fig. 12 (a) can be reflected so that the fluorescent light beam passing through the cylindrical diaphragm module 172 forms a fluorescent light beam having a cross section as shown in fig. 12 (B). Since the light intensity distribution of the fluorescent light beam is generally strong in the middle and weak in the periphery, after the fluorescence of the shadow portion in fig. 12 (a) is reflected and superimposed on the shadow portion in fig. 12 (B), the fluorescent light intensity of the shadow portion in fig. 12 (B) is increased more than that in the case where the reflection is not superimposed, so that the fluorescence of the shadow portion in fig. 12 (B) is correspondingly enhanced without change in the fluorescent light intensity of the middle portion. That is, the spot energy distribution formed by the fluorescent light beam passing through the cylindrical aperture module 172 can be made uniform.
As shown in fig. 11, the cross-sectional shape of the cylindrical diaphragm module 172 in fig. 11 (a), the cross-sectional shape of the cylindrical diaphragm module 172 in fig. 11 (B), and the cross-sectional shape of the cylindrical diaphragm module 172 in fig. 11 (C) are different from each other, but they satisfy the two conditions that the diameter of the fluorescent light beam at the light entrance P1 is equal to or larger than the cross-sectional diameter of the fluorescent light beam incident from the light entrance P1, and at least one condition that the diameter of the fluorescent light beam at the P2 is equal to or smaller than the cross-sectional diameter of the fluorescent light beam at the light entrance is present, therefore, the three types of cylindrical diaphragm modules 172 in fig. 11 can reflect the fluorescent light beam touching the inner wall based on the inner wall of the cylindrical cavity having the light beam reflection capability, and, as at the P2 in fig. 11, the cross-sectional diameter of the cylindrical cavity at the position is equal to or smaller than the cross-sectional diameter of the fluorescent light beam at the fluorescent light beam, so that part of the fluorescent light beam is reflected by the inner wall, the fluorescent light beam originally reflected from the edge is changed in the propagation direction, and the reflected light beam is changed, and the reflected light beam is overlapped on the edge of the light beam is scattered in the light receiving plane of the light receiving plane, and the light beam is scattered in the light receiving plane, and the light beam is uniformly is overlapped on the light beam, and the light beam is thus the light beam is spread.
In summary, based on the above-described embodiments, the cylindrical aperture module 172 that satisfies the above two conditions at will, like the three cylindrical aperture modules 172 shown in fig. 11, can improve the uniformity of the light intensity distribution of the light spot formed by the fluorescent light beam on the light-sensitive surface of the nonlinear photoelectric conversion module 13.
In a specific example, the cross-section of the cylindrical lumen of the cylindrical diaphragm module 172 decreases and then increases along the propagation direction of the fluorescent light beam, the cross-section being perpendicular to the central optical path of the fluorescent light beam passing through the cylindrical diaphragm module 172.
The section of the cylindrical inner cavity is firstly reduced and then increased, so that the light beam part of the fluorescent light beam which diverges towards the periphery is reflected by the inner wall, and the light beam part of the fluorescent light beam deviates towards the central light path direction of the fluorescent light beam in the cylindrical inner cavity, and the effect of improving the uniformity of the energy distribution of light spots formed by the fluorescent light beam is further achieved. For example, referring to fig. 12, fig. 12 is a schematic structural diagram of an embodiment of the present application, taking a square photosensitive surface of the nonlinear photoelectric conversion module 13 and a square cross section of the cylindrical diaphragm module 172 as an example, when the cylindrical diaphragm module 172 is not provided, as shown in fig. 12 (a), a portion of a fluorescent light beam generally diverges out of the photosensitive surface as shown in a shadow portion, as shown in fig. 12 (B), and under the action of the cylindrical diaphragm module 172, a portion of the light beam corresponding to the shadow portion from which the fluorescent light beam diverges out can be overlapped at a corresponding position in the square cross section by reflection of an inner wall, so that a light spot formed by the fluorescent light beam on the nonlinear photoelectric conversion module 13 will not generate a condition of uneven energy distribution due to divergence of a portion of the light beam, and accuracy of flow detection is improved.
The section with the smallest area among all sections in the cylindrical cavity is the focal plane of the optical path of the fluorescent light beam in the cylindrical diaphragm module 172.
Based on the above manner, by constructing the cylindrical diaphragm module 172 so that the inner wall of the cylindrical cavity can reflect the fluorescent light beam, a simple structure can be used to form the cylindrical diaphragm module 172 with flat-top light processing capability, thereby improving the accuracy of flow detection.
Further, the cross-sectional shape may be polygonal or circular.
Specifically, for example, if the cross-section is circular, the cylindrical cavity may be a cavity that is formed by two conical cavities and connects the tips of the two cones.
Further, the circle may be a perfect circle in particular, and the polygon may be a perfect polygon, such as a square.
Based on the above manner, the uniformity of the energy distribution of the light spot of the fluorescent light beam output by the tubular diaphragm module 172 can be improved, and the accuracy of the flow detection can be further improved.
In one embodiment, the ratio of the area of the light spot formed by the fluorescent light beam on the light sensing surface of the nonlinear photoelectric conversion module 13 to the area of the light sensing surface of the nonlinear photoelectric conversion module 13 is greater than 70%.
Specifically, as shown in fig. 13, a circle formed by a solid line represents the outline of the light spot, and a square formed by a solid line represents the outline of the light-sensitive surface of the nonlinear photoelectric conversion module 13.
As shown in fig. 13 (a), in the case where the fluorescent light beam forms the spot M only on the light sensing surface of the nonlinear photoelectric conversion module 13, the ratio of the spot area of the spot M to the area of the light sensing surface may be pi/4 at the maximum, about 78.54%. The ratio of the spot area to the area of the photosensitive surface may be other value of 70% or more, such as 71% or 75% or 78%, and is not limited herein.
As shown in fig. 13 (B), if the fluorescent light beam forms not only the flare N on the photosurface of the nonlinear photoelectric conversion module 13 but also a part of the flare N is located outside the photosurface, then, in the case where the area of the hatched portion where the flare N is located outside the photosurface as shown in fig. 13 (B) is not larger than the area where no flare exists on the photosurface, by reasonably setting the size and position of the flare on the photosurface, the ratio of the flare area formed by the fluorescent light beam on the photosurface of the nonlinear photoelectric conversion module 13 to the area of the photosurface of the nonlinear photoelectric conversion module 13 can be made larger than pi/4. Particularly, when the spot just exceeds the photosurface of the nonlinear photoelectric conversion module 13, although some fluorescence is not utilized, the spot area of the other part of fluorescence added to the photosurface by the spot is larger than the spot area of the unavailable part of fluorescence, and therefore, on the premise of ensuring that the utilization rate of the spot is sufficiently high as much as possible, the utilization rate of the photosurface of the nonlinear photoelectric conversion module 13 can be improved based on the mode.
The single photon avalanche diode array may be composed of a plurality of single photon avalanche diode units, and a gap exists between the single photon avalanche diode units, and when photons strike to the area, the avalanche is not caused, which is usually called a dead zone, so that the effective detection area is smaller than the total area of the single photon avalanche diode array. If the dead zone is considered, when the light spot just exceeds the photosurface of the nonlinear photoelectric conversion module 13, although a part of fluorescence cannot be utilized, the light spot area of the other part of fluorescence added by the light spot on the photosurface is larger, and the utilization rate of the photosurface of the nonlinear photoelectric conversion module 13 can be improved on the premise of ensuring that the utilization rate of the light spot is sufficiently high as much as possible. Based on the above mode, the proportion of the light spot area to the light sensitive surface area can be enlarged, so that the energy distribution of the light spots on the light sensitive surface is homogenized as much as possible, the accuracy of flow detection is improved, meanwhile, the utilization rate of the light sensitive surface of the nonlinear photoelectric conversion module 13 can be improved, and the waste of resources is reduced.
Further, by constructing the above-mentioned tubular diaphragm module 172 and making the inner wall of the tubular cavity have the ability to reflect the fluorescent light beam, a tubular diaphragm module 172 with flat-top light processing ability can be formed by a simpler structure, and the ratio of the area of the light spot formed by the fluorescent light beam passing through the tubular diaphragm module 172 on the light-sensitive surface of the nonlinear photoelectric conversion module 13 to the area of the light-sensitive surface of the nonlinear photoelectric conversion module 13 is greater than pi/4, and pi/4 is about 78.54%. The ratio of the areas may be specifically 80% or 95% or other values, which are not limited herein. Most fluorescence can be utilized through the cylindrical diaphragm module 172, so that the originally weak fluorescence intensity of the peripheral part is enhanced in the light spot formed on the light sensitive surface, the originally strong fluorescence intensity of the central part is unchanged, the energy distribution of the light spot formed by the fluorescence beam on the light sensitive surface of the nonlinear photoelectric conversion module 13 is uniform, the shape limitation of the square light sensitive area of the circular light spot and the nonlinear photoelectric conversion module 13 is broken through, the linear range of the nonlinear photoelectric conversion module 13 is greatly improved, and the accuracy of flow detection is further improved.
In the description of the present application, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the meaning of "plurality" is at least two, such as two, three, etc., unless explicitly defined otherwise.
Any process or method descriptions in flow charts or otherwise described herein may be understood as representing modules, segments, or portions of code which include one or more executable instructions for implementing specific logical functions or steps of the process, and further implementations are included within the scope of the preferred embodiment of the present application in which functions may be executed out of order from that shown or discussed, including substantially concurrently or in reverse order, depending on the functionality involved, as would be understood by those reasonably skilled in the art of the embodiments of the present application.
Logic and/or steps represented in the flowcharts or otherwise described herein, e.g., may be considered as a ordered listing of executable instructions for implementing logical functions, can be embodied in any computer-readable medium for use by or in connection with an instruction execution system, apparatus, or device (which can be a personal computer, server, network device, or other system that can fetch the instructions from the instruction execution system, apparatus, or device and execute the instructions). For the purposes of this description, a "computer-readable medium" can be any means that can contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device. More specific examples (a non-exhaustive list) of the computer-readable medium would include the following: an electrical connection (electronic device) having one or more wires, a portable computer diskette (magnetic device), a Random Access Memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber device, and a portable compact disc read-only memory (CDROM). In addition, the computer readable medium may even be paper or other suitable medium on which the program is printed, as the program may be electronically captured, via, for instance, optical scanning of the paper or other medium, then compiled, interpreted or otherwise processed in a suitable manner, if necessary, and then stored in a computer memory.
The foregoing description is only of embodiments of the present application, and is not intended to limit the scope of the patent application, and all equivalent structures or equivalent processes using the descriptions and the contents of the present application or other related technical fields are included in the scope of the patent application.

Claims (10)

1. A blood analysis device, comprising:
an optical flow chamber through which a liquid to be measured flows;
the light source is used for emitting a coherent light beam towards the optical flow chamber, the coherent light beam irradiates particles in the liquid to be detected flowing through the optical flow chamber, and fluorescent light beams are generated through excitation, wherein the particles contain fluorescent dye liquid;
the nonlinear photoelectric conversion module is used for carrying out photoelectric conversion on the fluorescent light beam;
wherein the difference between the wavelength of the coherent light beam and the wavelength of the maximum excitation peak of the fluorescent dye is less than 10 nanometers,
and/or the difference between the wavelength of the coherent light beam and the wavelength of the maximum emission peak of the fluorescent dye is greater than 15 nanometers.
2. The blood analysis device according to claim 1, wherein a difference between a wavelength of a maximum excitation peak of the fluorescent dye and a wavelength of a maximum emission peak of the fluorescent dye is greater than 10 nm,
And/or the maximum emission peak wavelength of the fluorescent light beam is 650-675 nanometers.
3. The blood analysis device according to claim 1, wherein,
the coherent light beam irradiates particles in the liquid to be detected flowing in the optical flow chamber to excite and generate fluorescent light beams and scatter the fluorescent light beams to form scattered light beams;
the blood analysis device also comprises a light splitting module and a linear photoelectric conversion module;
the light splitting module is positioned on a light path of the coincidence center of the fluorescent light beam and the scattered light beam, and is used for transmitting the fluorescent light beam and reflecting the scattered light beam;
the linear photoelectric conversion module is used for carrying out photoelectric conversion on the scattered light beams;
the reflection wave band of the light splitting module is partially overlapped with the transmission wave band of the light splitting module;
the wavelength of the scattered light beam is smaller than the minimum wavelength of the transmission wave band of the light splitting module, and the difference between the wavelength of the scattered light beam and the wavelength of the minimum wavelength of the transmission wave band of the light splitting module is larger than 5 nanometers,
and/or, the peak wavelength of the fluorescent light beam is greater than the maximum wavelength of the reflection band of the light splitting module, and the difference between the peak wavelength of the fluorescent light beam and the wavelength of the maximum wavelength of the reflection band of the light splitting module is greater than 5 nanometers.
4. A blood analysis device according to claim 3 wherein the light splitting module is a dichroic mirror;
the transmittance of the dichroic mirror for the fluorescent light beam is greater than 90%,
and/or the dichroic mirror has a reflectivity of more than 95% for the scattered light beam,
and/or the wavelength error of the dichroic mirror is between-0.5% -0.5% of the edge wavelength,
and/or, the wavelength range of the dichroic mirror is between 250 nanometers and 1000 nanometers,
and/or the steepness of the dichroic mirror is less than 4% of the edge wavelength,
and/or the dichroic mirror has a transmitted wavefront difference of less than 0.01λ per inch at 632.8 nanometers.
5. The blood analysis device according to claim 1, wherein,
the peak wavelength of the fluorescent light beam is larger than the peak sensitivity wavelength of the nonlinear photoelectric conversion module, the difference between the peak wavelength of the fluorescent light beam and the peak sensitivity wavelength of the nonlinear photoelectric conversion module is smaller than 280 nanometers,
and/or the photosensitivity of the nonlinear photoelectric conversion module is greater than 7×10 4 The weight of the alloy is set to be the same as the weight of the alloy,
and/or, the overvoltage of the nonlinear photoelectric conversion module is greater than 0.5 volt,
and/or, the overvoltage of the nonlinear photoelectric conversion module is less than 4.5 volts.
6. The blood analysis device according to claim 1, wherein,
the peak wavelength of the fluorescent light beam is larger than the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module, and the difference between the peak wavelength of the fluorescent light beam and the peak wavelength of the photon detection efficiency of the nonlinear photoelectric conversion module is smaller than 310 nanometers,
and/or the photon detection efficiency of the nonlinear photoelectric conversion module is greater than 10%,
and/or, the reverse voltage of the nonlinear photoelectric conversion module is greater than the device breakdown voltage and the overvoltage of the nonlinear photoelectric conversion module is greater than 0.5 volt.
7. The blood analysis device according to claim 1, wherein,
the pixel size of the photosurface of each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module is more than or equal to 25 micrometers,
and/or the total number of all the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module is greater than 500,
and/or each nonlinear photoelectric conversion unit in the nonlinear photoelectric conversion module has a photon detection efficiency of greater than 12%,
and/or the total area of the photosurface of the nonlinear photoelectric conversion module is more than or equal to 36 square millimeters,
And/or the sum of the areas of the photosurfaces of all the nonlinear photoelectric conversion units in the nonlinear photoelectric conversion module accounts for not less than 70% of the total area of the photosurfaces of the nonlinear photoelectric conversion module.
8. The blood analysis device according to claim 1, wherein,
the sampling pulse period of the nonlinear photoelectric conversion module comprises a rising section and a falling section;
the total time length of the rising section is respectively in positive correlation with the total capacitance of the nonlinear photoelectric conversion module and the resistance of the nonlinear photoelectric conversion unit,
and/or, the total duration of the descending section is in positive correlation with the total capacitance and the quenching resistance of the nonlinear photoelectric conversion module respectively;
the total duration of the sampling pulse period of the nonlinear photoelectric conversion module is not more than one tenth of the total duration of the pulse width corresponding to the particles in the liquid to be detected.
9. The blood analysis device according to any one of claim 1 to 8, wherein,
a flat top light module and/or a cylindrical diaphragm module are/is arranged between the optical flow chamber and the nonlinear photoelectric conversion module;
the flat-top optical module is used for converting the fluorescent light beam into a flat-top light beam, and the nonlinear photoelectric conversion module is used for performing photoelectric conversion on the fluorescent light beam converted by the flat-top optical module;
The cylindrical diaphragm module is provided with a cylindrical inner cavity, the fluorescent light beam enters from a light inlet of the cylindrical inner cavity and exits from a light outlet of the cylindrical inner cavity, the inner wall of the cylindrical inner cavity is arranged to reflect the fluorescent light beam entering the cylindrical inner cavity, and the nonlinear photoelectric conversion module is used for performing photoelectric conversion on the fluorescent light beam exiting from the light outlet.
10. The blood analysis device according to claim 9, wherein the blood analysis device comprises,
the diameter of the light inlet is larger than or equal to the diameter of the cross section of the fluorescent light beam incident from the light inlet, and the diameter of the cross section of at least one part of the cylindrical inner cavity behind the light inlet is smaller than or equal to the diameter of the cross section of the fluorescent light beam at the corresponding position;
each of the cross sections is perpendicular to a central optical path of the fluorescent light beam at a corresponding position.
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