WO2024108569A1 - 磁珠检测的方法、装置及磁珠检测光学系统 - Google Patents

磁珠检测的方法、装置及磁珠检测光学系统 Download PDF

Info

Publication number
WO2024108569A1
WO2024108569A1 PCT/CN2022/134430 CN2022134430W WO2024108569A1 WO 2024108569 A1 WO2024108569 A1 WO 2024108569A1 CN 2022134430 W CN2022134430 W CN 2022134430W WO 2024108569 A1 WO2024108569 A1 WO 2024108569A1
Authority
WO
WIPO (PCT)
Prior art keywords
magnetic bead
detected
light source
sample
contour
Prior art date
Application number
PCT/CN2022/134430
Other languages
English (en)
French (fr)
Inventor
邓茜
杨斌
姜鹤鸣
赵学江
Original Assignee
深圳华大智造科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳华大智造科技股份有限公司 filed Critical 深圳华大智造科技股份有限公司
Priority to PCT/CN2022/134430 priority Critical patent/WO2024108569A1/zh
Publication of WO2024108569A1 publication Critical patent/WO2024108569A1/zh

Links

Images

Classifications

    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters

Definitions

  • chemiluminescence which has the advantages of high sensitivity, automation, and flexible configuration.
  • This technology has gradually replaced traditional methods such as colloidal gold and enzyme-linked fluorescence detection.
  • chemiluminescence technology can only perform quantitative detection, classification detection is required to achieve simultaneous detection of multiple markers and very few samples; classification detection is inefficient and time-consuming, resulting in higher time costs and consumables costs. It is impossible to respond quickly and promptly to the needs of obtaining test results for multiple proteins and samples of different concentrations in a short period of time.
  • a magnetic bead detection optical system which includes: a contour light source module, an excitation light source module and an imaging module;
  • the contour light source module is used to emit detection light to the sample to be detected having magnetic beads and illuminate the contour of the magnetic beads to generate a contour light signal;
  • the excitation light source module is used to emit laser light to the sample to be detected to excite the magnetic beads to generate fluorescent signals
  • the imaging module comprises a light guide and an image acquisition device, wherein:
  • the image acquisition device acquires a first optical image corresponding to the contour light signal and a second optical image corresponding to the fluorescence signal.
  • the light guide is a first dichroic mirror, which is located between the sample to be detected and the excitation light source module, the laser generated by the excitation light source module is transmitted to the sample to be detected by the first dichroic mirror, and the fluorescence signal is reflected by the first dichroic mirror to the image acquisition device.
  • the sample to be detected is located between the first dichroic mirror and the contour light source module, and the contour light signal generated by the detection light emitted by the contour light source module illuminating the magnetic beads is reflected by the first dichroic mirror to the image acquisition device.
  • the contour light source module further includes: an LED light source and a second dichroic mirror;
  • the LED light source is used to emit the detection light to the second dichroic mirror
  • the second dichroic mirror reflects the detection light to the sample to be detected.
  • the contour light module further includes a reflective ring which is sleeved on the periphery of the LED light source and extends toward the second dichroic mirror.
  • the reflective ring is in the shape of a tapered cylinder whose diameter increases toward the second dichroic mirror.
  • the contour light module further comprises an illumination filter installed on a side of the reflective ring away from the LED light source.
  • the contour light module further comprises a matte cover arranged on a side of the second dichroic mirror away from the LED light source.
  • the excitation light source module includes a laser, and the laser is used to emit laser light; the first dichroic mirror transmits the laser light to the sample to be detected.
  • the excitation light source module further includes: a reflector
  • the reflecting mirror is used to reflect the laser light emitted by the laser to the first dichroic mirror.
  • the image acquisition device includes an image sensor and a fluorescent filter located between the image sensor and the light guide; the fluorescent filter filters the collected fluorescent signal transmitted by the first dichroic mirror, and injects the filtered fluorescent signal into the image acquisition device.
  • the image acquisition device further includes: a telecentric lens located between the light guide and the fluorescent filter.
  • system further comprises an imaging module adjustment and fixing module
  • the imaging module adjustment and fixing module comprises a first dichroic mirror adjustment component and a lens fixing and adjusting component, and is used for fixing the imaging module and adjusting the imaging angle.
  • the system further includes an excitation light source adjustment and fixing module, including a light source fixing seat, a light source adjustment seat and a reflector adjustment assembly, which is used to fix the laser and adjust the laser light path.
  • an excitation light source adjustment and fixing module including a light source fixing seat, a light source adjustment seat and a reflector adjustment assembly, which is used to fix the laser and adjust the laser light path.
  • a magnetic bead detection device comprising the magnetic bead detection optical system described in the first aspect of the present disclosure.
  • the device further comprises an analysis module connected to the imaging module, wherein the analysis module receives the first optical image and the second optical image and performs the following steps:
  • the concentration distribution of different types of magnetic beads is statistically analyzed by combining the magnetic bead profile and the fluorescent grayscale fluorescence signal.
  • a method for magnetic bead detection comprising:
  • the laser is used to irradiate the magnetic bead sample to be detected, and the magnetic beads are excited to generate fluorescent signals;
  • the type and concentration distribution of the magnetic beads are determined based on the first optical image information and the second optical image information.
  • the method before irradiating the magnetic bead sample to be detected with laser, the method further includes:
  • the magnetic bead sample to be detected is dyed based on a preselected dye; wherein the wavelength of the laser does not include the fluorescence emission spectrum of the preselected dye.
  • the method further comprises:
  • the laser light passing through the magnetic bead sample to be detected is processed to eliminate the background light by using a light-extinguishing mask.
  • illuminating the magnetic bead sample to be detected based on a contour light source includes:
  • the uniformly straightened illumination light is reflected by a dichroic mirror to illuminate the magnetic bead sample to be detected and the contour information of the magnetic beads; wherein the wavelength band of the illumination light includes the fluorescence excitation spectrum of the magnetic bead sample to be detected.
  • the acquiring first optical image information corresponding to the fluorescence signal includes:
  • the fluorescent signal is reflected into an image acquisition device
  • the first optical image corresponding to the magnetic bead sample to be detected is obtained according to the image acquisition device.
  • the acquiring second optical image information corresponding to the contour light signal includes:
  • the contour light signal is reflected into an image acquisition device
  • the second optical image corresponding to the magnetic bead sample to be detected is obtained according to the image acquisition device.
  • an electronic device including:
  • the memory stores instructions that can be executed by the at least one processor, and the instructions are executed by the at least one processor to enable the at least one processor to execute the method described in the third aspect.
  • a non-transitory computer-readable storage medium storing computer instructions, wherein the computer instructions are used to enable the computer to execute the method described in the third aspect above.
  • a computer program product comprising a computer program, wherein when the computer program is executed by a processor, the method described in the third aspect is implemented.
  • the present disclosure provides a method, device and optical system for detecting magnetic beads, which utilize laser to illuminate a sample of magnetic beads to be detected, and excite the magnetic beads to generate a fluorescent signal; illuminate the sample of magnetic beads to be detected based on a contour light source, and generate a contour light signal of the magnetic beads; obtain first optical image information corresponding to the fluorescent signal; obtain second optical image information corresponding to the contour light signal; and determine the type and concentration distribution of the magnetic beads by combining the first optical image information and the second optical image information.
  • the embodiment of the present disclosure obtains the fluorescent signal and the contour light signal of the sample to be detected for imaging, and identifies the type and concentration of the protein; it is possible to detect protein samples of different concentrations and types to be detected, thereby improving the detection efficiency of the sample.
  • FIG1 is a schematic diagram of an optical system for detecting magnetic beads provided in an embodiment of the present disclosure
  • FIG2 is a schematic diagram of an optical path of a magnetic bead detection optical system provided in an embodiment of the present disclosure
  • FIG3 is a cross-sectional view along line A-A when the magnetic bead detection optical system shown in FIG1 is used for detection in an embodiment of the present disclosure
  • FIG4 is a schematic structural diagram of a contour light source module in the magnetic bead detection optical system shown in FIG3 ;
  • FIG5 is a schematic diagram of the structure of an image acquisition device provided by an embodiment of the present disclosure.
  • FIG6 is a schematic diagram of another viewing angle of a magnetic bead detection optical system provided by an embodiment of the present disclosure.
  • FIG7 is an enlarged schematic diagram of a portion P of the magnetic bead detection optical system shown in FIG6 ;
  • FIG8 is a schematic diagram of the structure of a reflector adjustment assembly provided by an embodiment of the present disclosure.
  • FIG9 is an exploded schematic diagram of the reflector adjustment assembly shown in FIG8 ;
  • FIG10 is a schematic diagram of the structure of a magnetic bead detection device provided in an embodiment of the present disclosure.
  • FIG11 is a schematic flow chart of a method for magnetic bead detection provided in an embodiment of the present disclosure.
  • FIG. 12 is a schematic block diagram of an example electronic device 400 provided according to an embodiment of the present disclosure.
  • FIG1 is a schematic diagram of a magnetic bead detection optical system provided by an embodiment of the present disclosure.
  • the protein joint detection device includes: a contour light source module 11, an excitation light source module 12, and an imaging module 13.
  • the "magnetic beads" described in the present application can be coded microspheres, which can be superparamagnetic microspheres with a small particle size, and/or microspheres with metal particles (which can generate magnetism under the action of an external magnetic field).
  • the shape of the magnetic beads is not limited and can be an irregular shape.
  • the type of magnetic beads can be identified from the spherical shape based on the contour information in the image obtained under the contour light.
  • the contour light source module 11 is used to emit detection light to the sample to be detected having magnetic beads and illuminate the contour of the magnetic beads to generate a contour light signal.
  • the contour light source module 11 is disposed above the sample to be detected. It should be noted that the contour light source module 11 is used to provide a light source for the sample to be detected, and the light emitted by the contour light source module 11 can be irradiated to the sample to be detected.
  • the embodiment of the present disclosure does not limit the installation position of the contour light source module 11.
  • the contour light source module 11 can also be installed below the sample to be detected. The foregoing description is merely exemplary and does not constitute a limitation of the present disclosure.
  • the excitation light source module 12 is used to emit laser light to the sample to be detected, so as to excite the magnetic bead sample to generate a fluorescent signal.
  • the excitation light source module 12 is arranged below the magnetic bead sample to be detected.
  • the excitation light source module 12 is used to generate laser and irradiate the sample to be detected to generate fluorescence; the wavelength of the excitation light source of the excitation light source module 12 matches the fluorescence excitation spectrum of the magnetic bead sample to be detected carrying the dye, and is away from the fluorescence emission spectrum of the dye.
  • the dye is pre-selected according to the wavelength of the laser generated by the excitation light source module 12.
  • the imaging module 13 includes a light guide 131 and an image acquisition device 132, wherein the light guide 131 is located between the sample to be detected and the image acquisition device 132, and is used to transmit and guide the contour light signal and the fluorescent signal to the image acquisition device 132 in sequence.
  • the image acquisition device 132 acquires a first optical image corresponding to the contour light signal and a second optical image corresponding to the fluorescence signal.
  • the wavelength band of the light source generated by the contour light source module 11 needs to include the wavelength band of the fluorescence excited by the magnetic bead sample to be detected.
  • the light guide 131 can transmit the excitation light source generated by the excitation light source module 12, and the excitation light source can illuminate the magnetic bead sample to be detected to excite and generate fluorescence.
  • the light guide 131 reflects the magnetic bead contour generated by the contour light source module 11 irradiating the magnetic bead sample to be detected and the excited fluorescence to the image acquisition device 132.
  • the present disclosure provides a magnetic bead detection optical system, which uses laser to irradiate a magnetic bead sample to be detected, excites the magnetic beads to generate a fluorescent signal; illuminates the magnetic bead sample to be detected based on a contour light source, generates a contour light signal of the magnetic beads; obtains first optical image information corresponding to the fluorescent signal; obtains second optical image information corresponding to the contour light signal; and determines the type and concentration distribution of the magnetic beads by combining the first optical image information and the second optical image information.
  • the embodiment of the present disclosure can be used to identify the type and concentration of proteins with corresponding magnetic beads by acquiring the fluorescent signal and the contour light signal of the sample to be detected for imaging; it can realize the detection of protein samples of different concentrations and types, thereby improving the detection efficiency of samples.
  • the light guide 131 is a first dichroic mirror 1311, and the first dichroic mirror 1311 is transmissively located between the sample to be detected 20 and the excitation light source module 12, and the laser generated by the excitation light source module 12 is transmitted by the first dichroic mirror 1311 to the sample to be detected 20, and the fluorescence signal is reflected by the first dichroic mirror 1311 to the image acquisition device 132.
  • FIG3 is a cross-sectional view along the A-A line when the magnetic bead detection optical system shown in FIG1 is used to detect the sample 20 to be detected.
  • the first dichroic mirror 1311 transmits the laser generated by the excitation light source module 12 to the sample 20 to be detected, and the first dichroic mirror 1311 then reflects the generated fluorescence signal to the image acquisition device 132.
  • the position of the first dichroic mirror 1311 is adjustable to achieve the adjustable light path; thereby, the laser generated by the excitation light source module 12 can better illuminate the magnetic beads in the sample 20 to be detected, so as to generate a fluorescence signal, and reflect the fluorescence signal to the image acquisition device 132.
  • the sample to be detected 20 is located between the first dichroic mirror 1311 and the contour light source module 11 , and the contour light signal generated by the detection light emitted by the contour light source module 11 illuminating the magnetic beads is reflected by the first dichroic mirror 1311 to the image acquisition device 132 .
  • the first dichroic mirror 1311 reflects the contour light signal to the image acquisition device 132. It should be noted that the wavelength band of the detection light generated by the contour light source module 11 cannot pass through the first dichroic mirror 1311, while the laser generated by the excitation light source module 12 can pass through the first dichroic mirror 1311.
  • the contour light source module 11 further includes: an LED light source 111 and a second dichroic mirror 112; the LED light source 111 is used to emit the detection light to the second dichroic mirror 112; the second dichroic mirror 112 reflects the detection light to the sample 20 to be detected.
  • Figure 4 is a schematic diagram of the structure of a contour light source module provided in the embodiment of the present disclosure.
  • the contour light source module 11 generates detection light by the LED light source 111, and then the second dichroic mirror 112 reflects the detection light to the sample to be detected 20, so as to illuminate the contour of the magnetic beads in the sample to be detected 20 to generate a contour light signal.
  • the contour light source module 11 further includes a reflective ring 113 that is sleeved on the outer periphery of the LED light source 111 and extends toward the second dichroic mirror 112.
  • the reflective ring 113 is a conical cylindrical shape whose diameter increases toward the second dichroic mirror 112.
  • a laser lens for example, may be used to replace the reflective ring 113, as long as the component replacing the reflective ring can produce a focusing and uniform light effect.
  • an enlarged conical cylindrical reflective ring 113 extending toward the second dichroic mirror 112 is provided on the periphery of the LED light source 111.
  • the reflective ring 113 straightens the detection light generated by the LED light source 111 to improve the utilization rate of the light and the uniformity of the illumination.
  • the contour light source module 11 further includes an illumination filter 114 installed on a side of the reflective ring 113 away from the LED light source.
  • the detection light is filtered out through the illumination filter 114 to remove the light that interferes with the detection. It should be noted that the embodiment of the present disclosure does not limit the type of illumination filter 114 used.
  • the contour light source module further includes a matte cover 115 which is disposed on a side of the second dichroic mirror 112 away from the LED light source 111 .
  • the second dichroic mirror 112 reflects the detection light generated by the LED light source 111 to the sample to be detected 20; after the laser generated by the excitation light source module 12 is transmitted to the sample to be detected 20, part of the laser will pass through the sample to be detected 20 and be emitted to the second dichroic mirror 112.
  • the laser After the second dichroic mirror 112 transmits the emitted laser, the laser is emitted into the extinction cover 115; the extinction cover 115 has a light-absorbing surface that performs multiple reflections and absorption, so that the laser returning to the sample to be detected 20 is greatly reduced, reducing the imaging background, and at the same time, it can effectively collect the laser to avoid stray light.
  • the excitation light source module 12 includes a laser 121 and a reflector 122, wherein the laser 121 is used to emit laser light; and the first dichroic mirror 1311 transmits the laser light to the sample to be detected 20.
  • the reflector 122 is used to reflect the laser light emitted by the laser to the first dichroic mirror 1311.
  • the reflector 122 reflects the laser light to the first dichroic mirror 1311, and the laser light excites the magnetic beads in the sample to be detected 20 to emit fluorescence after passing through the first dichroic mirror 1311.
  • the laser 121 can also be directly directed to the sample to be detected 20 to irradiate the magnetic beads with laser light, without the need to set a reflector.
  • the image acquisition device 132 includes an image sensor 1321, and a fluorescent filter 1322 located between the image sensor 1321 and the light guide 131; the fluorescent filter 1322 filters the collected fluorescent signal transmitted by the first dichroic mirror 1311, and injects the filtered fluorescent signal into the image acquisition device 132.
  • the image acquisition device 132 also includes: a telecentric lens 1323 located between the light guide 131 and the fluorescent filter. It should be understood that in other embodiments of the present invention, other industrial lenses that can meet the resolution requirements and field of view requirements can also be selected to replace the telecentric lens.
  • FIG5 is a schematic diagram of the structure of an image acquisition device provided by the embodiment of the present disclosure.
  • the fluorescence signal and the contour light signal are first transmitted to the telecentric lens 1323 via the first dichroic mirror 1311.
  • a large field of view telecentric lens is selected to make the imaging field of view large, so that the single hole size of the selected detection plate can be matched to take one or more photos.
  • the larger the single photo area the smaller the number of photos required for a single hole, the higher the detection efficiency, and the lower the detection cost.
  • the fluorescence signal and the contour light signal are then transmitted to the fluorescence filter 1322 via the telecentric lens 1323, and the fluorescence filter 1322 filters the laser and ambient light in the fluorescence signal and the contour light signal.
  • the messy light to reduce the impact on the imaging result After filtering by the fluorescence filter 1322, the fluorescence signal and the contour light signal are acquired by the image sensor 1321, and the fluorescence signal and the contour light signal are converted into corresponding image information.
  • the system further includes an imaging module adjustment and fixing module
  • the imaging module adjustment and fixing module 14 includes a first dichroic mirror adjustment component 141 and a lens fixing and adjusting component 142, and is used to fix the imaging module 13 and adjust the imaging angle.
  • the first dichroic mirror adjustment component 141 mainly ensures that the installation angle of the first dichroic mirror meets the 45-degree incidence, and ensures that the position of the optical axis is consistent with the ideal optical axis as much as possible.
  • the lens fixing adjustment component 142 mainly plays the role of fixing the position of the entire imaging system; at the same time, the position of the entire imaging module 13 in three directions of XYZ can also be adjusted, and the tilt and pitch angles of the imaging system can be adjusted at the same time, so as to achieve the coincidence of the optical axis of the entire imaging light path with the optical axis of the illumination system reflected by the first dichroic mirror 1311; thereby achieving that the magnetic bead hole on the detection board can fall within the focusing range of the detection system.
  • the system also includes an excitation light source adjustment and fixing module 15 , including a light source fixing seat 151 , a light source adjustment seat 152 and a reflector adjustment assembly 153 , for fixing the laser 121 and adjusting the laser light path.
  • an excitation light source adjustment and fixing module 15 including a light source fixing seat 151 , a light source adjustment seat 152 and a reflector adjustment assembly 153 , for fixing the laser 121 and adjusting the laser light path.
  • the laser 121 is fixed by the light source fixing seat 151, and the light source adjustment seat 152 is mainly used to adjust the emission angle of the laser light.
  • the reflector adjustment assembly 153 is composed of a reflector fixing frame 1531, an adjustment seat 1532, and a light shielding cover 1533. The reflector adjustment assembly 153 mainly ensures that the installation angle of the reflector 122 meets the 45-degree incidence, and ensures that the position of the optical axis is consistent with the ideal optical axis as much as possible.
  • FIG10 is a schematic diagram of the structure of a magnetic bead detection device provided in an embodiment of the present disclosure, wherein the device comprises: a magnetic bead detection optical system 21 and an analysis module 22 .
  • the device further includes an analysis module 22 connected to the imaging module, the analysis module 22 receives the first optical image and the second optical image, and performs the following steps:
  • the concentration distribution of different types of magnetic beads is statistically analyzed by combining the magnetic bead profile and the fluorescent grayscale fluorescence signal.
  • the present invention also provides a magnetic bead detection method. Since the device embodiment of the present invention corresponds to the above-mentioned method embodiment, details not disclosed in the device embodiment can be referred to the above-mentioned method embodiment, and will not be repeated in the present invention.
  • FIG. 11 is a schematic flow chart of a method for magnetic bead detection provided in an embodiment of the present disclosure.
  • the method comprises the following steps:
  • Step 301 irradiate the magnetic bead sample to be detected with laser to excite the magnetic beads to generate fluorescent signals.
  • the laser generated by the excitation light source module is used to irradiate the magnetic bead sample to generate fluorescence; the wavelength of the excitation light source of the excitation light source module matches the fluorescence excitation spectrum of the dye carried by the magnetic bead sample to be detected, while being far away from the fluorescence emission spectrum of the dye.
  • Step 302 Acquire first optical image information corresponding to the fluorescence signal.
  • Step 301' illuminating the magnetic bead sample to be detected based on a contour light source to generate a contour light signal of the magnetic beads.
  • the contour light source module provides a light source for the magnetic bead sample to be detected, so that the magnetic bead sample to be detected can be irradiated, and then the contour light signal of the magnetic beads can be obtained.
  • the magnetic bead detection device obtains first optical image information about the magnetic bead sample to be detected by transmitting the obtained fluorescence to the imaging module.
  • Step 302' obtaining second optical image information corresponding to the contour light signal.
  • the magnetic bead detection device obtains second optical image information about the magnetic bead sample to be detected by transmitting the obtained profile to the imaging module.
  • Step 303 Determine the type and concentration distribution of the magnetic beads by combining the first optical image information and the second optical image information.
  • the order of obtaining the first optical image information and the second optical image information is not limited.
  • the sample to be detected can be irradiated with contour light to obtain the second optical image information, and then the contour light is turned on to turn on the laser light source to obtain the first optical image information.
  • the contour of the magnetic beads can characterize the type of protein bound to the magnetic beads, and the brightness of the fluorescence can characterize the concentration distribution of the magnetic beads. Based on the fluorescence and contour information reflected in the image information, the type of magnetic beads and the concentration distribution can be further determined.
  • the present disclosure provides a method for detecting magnetic beads, which uses laser to irradiate a sample of magnetic beads to be detected, and excites the magnetic beads to generate a fluorescent signal; illuminates the sample of magnetic beads to be detected based on a contour light source, and generates a contour light signal of the magnetic beads; obtains first optical image information corresponding to the fluorescent signal; obtains second optical image information corresponding to the contour light signal; and determines the type and concentration distribution of the magnetic beads by combining the first optical image information and the second optical image information.
  • the embodiment of the present disclosure obtains the fluorescent signal and the contour light signal of the sample to be detected for imaging, identifies the type and concentration of the protein; and can detect protein samples of different concentrations and types to be detected, thereby improving the detection efficiency of the sample.
  • the method before irradiating the magnetic bead sample to be detected with laser, the method further includes:
  • the magnetic bead sample to be detected is dyed based on a preselected dye; wherein the wavelength of the laser does not include the fluorescence emission spectrum of the preselected dye.
  • the magnetic bead sample to be detected needs to be dyed.
  • the fluorescence excitation spectrum of the dye matches the wavelength of the excitation light source, and the wavelength of the excitation light source should be far away from the fluorescence emission spectrum of the dye.
  • the method further includes:
  • the laser light passing through the magnetic bead sample to be detected is processed to eliminate the background light by using a light-extinguishing mask.
  • the laser After passing through the magnetic bead sample to be detected, the laser will be reflected back to the original light path in the magnetic bead detection device, affecting the experimental results. Therefore, it is necessary to extinct the laser that has passed through the magnetic bead sample to be detected.
  • the laser is reflected to the inside of the extinction cover by the reflector inside the extinction cover, and the inner surface of the extinction cover is made of a material with light-absorbing properties, and is absorbed through multiple reflections. This prevents stray light from interfering with the experiment and preventing accidents caused by laser emission outside the device.
  • illuminating the magnetic bead sample to be detected based on a contour light source includes:
  • the uniformly straightened illumination light is reflected by a dichroic mirror to illuminate the magnetic bead sample to be detected and the contour information of the magnetic beads; wherein the wavelength band of the illumination light includes the fluorescence excitation spectrum of the magnetic bead sample to be detected.
  • the contour light source is straightened by using a focusing device (including but not limited to a focusing lens or a reflective ring) to improve the utilization rate of light and the uniformity of illumination.
  • the contour light source is filtered through an illumination filter to remove light that interferes with the detection.
  • the contour light source illuminates the contour of the magnetic bead sample to be detected; in order for the contour light source to be able to illuminate the contour of the magnetic bead sample to be detected, the wavelength of the contour light source needs to include the wavelength of the fluorescence excited by the magnetic bead sample to be detected.
  • the acquiring of first optical image information corresponding to the fluorescence signal includes:
  • the fluorescent signal is reflected into an image acquisition device
  • the first optical information corresponding to the magnetic bead sample to be detected is obtained according to an image acquisition device.
  • a laser is transmitted by a dichroic mirror, and the laser irradiates the magnetic bead sample to be detected to generate fluorescence, and the dichroic mirror reflects the generated fluorescence to the image acquisition device.
  • the image acquisition device outputs the first optical information to a computer device, and the computer device further determines the type of magnetic beads and the distribution of concentration.
  • the acquiring of the second optical image information corresponding to the contour light signal includes:
  • the contour light signal is reflected into an image acquisition device
  • the second optical image corresponding to the magnetic bead sample to be detected is obtained according to the image acquisition device.
  • the detection light is reflected by a dichroic mirror, and the detection light irradiates the magnetic bead sample to be detected to generate a contour light signal.
  • the dichroic mirror reflects the contour light signal generated by the contour light source irradiating the magnetic bead sample to be detected to the image acquisition device.
  • the image acquisition device outputs the second optical information to the computer device, and the computer device further determines the type of magnetic beads and the distribution of concentration.
  • the present disclosure also provides an electronic device, a readable storage medium and a computer program product.
  • FIG. 12 shows a schematic block diagram of an example electronic device 400 that can be used to implement an embodiment of the present disclosure.
  • the electronic device is intended to represent various forms of digital computers, such as laptop computers, desktop computers, workbenches, personal digital assistants, servers, blade servers, mainframe computers, and other suitable computers.
  • the electronic device can also represent various forms of mobile devices, such as personal digital processing, cellular phones, smart phones, wearable devices, and other similar computing devices.
  • the components shown herein, their connections and relationships, and their functions are merely examples and are not intended to limit the implementation of the present disclosure described and/or required herein.
  • the device 400 includes a computing unit 401, which can perform various appropriate actions and processes according to a computer program stored in a ROM (Read-Only Memory) 402 or a computer program loaded from a storage unit 408 into a RAM (Random Access Memory) 403.
  • a ROM Read-Only Memory
  • RAM Random Access Memory
  • various programs and data required for the operation of the device 400 can also be stored.
  • the computing unit 401, the ROM 402, and the RAM 403 are connected to each other via a bus 404.
  • An I/O (Input/Output) interface 405 is also connected to the bus 404.
  • a number of components in the device 400 are connected to the I/O interface 405, including: an input unit 406, such as a keyboard, a mouse, etc.; an output unit 407, such as various types of displays, speakers, etc.; a storage unit 408, such as a disk, an optical disk, etc.; and a communication unit 409, such as a network card, a modem, a wireless communication transceiver, etc.
  • the communication unit 409 allows the device 400 to exchange information/data with other devices through a computer network such as the Internet and/or various telecommunication networks.
  • the computing unit 401 may be a variety of general and/or special processing components with processing and computing capabilities. Some examples of the computing unit 401 include, but are not limited to, a CPU (Central Processing Unit), a GPU (Graphic Processing Units), various dedicated AI (Artificial Intelligence) computing chips, various computing units running machine learning model algorithms, a DSP (Digital Signal Processor), and any appropriate processor, controller, microcontroller, etc.
  • the computing unit 401 performs the various methods and processes described above, such as the method of magnetic bead detection.
  • the method of magnetic bead detection may be implemented as a computer software program, which is tangibly contained in a machine-readable medium, such as a storage unit 408.
  • part or all of the computer program may be loaded and/or installed on the device 400 via the ROM 402 and/or the communication unit 409.
  • the computer program When the computer program is loaded into the RAM 403 and executed by the computing unit 401, one or more steps of the method described above may be performed.
  • the computing unit 401 may be configured to perform the aforementioned magnetic bead detection method in any other appropriate manner (eg, by means of firmware).
  • Various embodiments of the systems and techniques described above herein may be implemented in digital electronic circuit systems, integrated circuit systems, FPGAs (Field Programmable Gate Array), ASICs (Application-Specific Integrated Circuit), ASSPs (Application Specific Standard Product), SOCs (System On Chip), CPLDs (Complex Programmable Logic Device), computer hardware, firmware, software, and/or combinations thereof.
  • FPGAs Field Programmable Gate Array
  • ASICs Application-Specific Integrated Circuit
  • ASSPs Application Specific Standard Product
  • SOCs System On Chip
  • CPLDs Complex Programmable Logic Device
  • These various embodiments may include: being implemented in one or more computer programs that are executable and/or interpreted on a programmable system that includes at least one programmable processor that may be a special purpose or general purpose programmable processor that may receive data and instructions from a storage system, at least one input device, and at least one output device, and transmit data and instructions to the storage system, the at least one input device, and the at least one output device.
  • a programmable processor may be a special purpose or general purpose programmable processor that may receive data and instructions from a storage system, at least one input device, and at least one output device, and transmit data and instructions to the storage system, the at least one input device, and the at least one output device.
  • the program code for implementing the method of the present disclosure may be written in any combination of one or more programming languages. These program codes may be provided to a processor or controller of a general-purpose computer, a special-purpose computer, or other programmable data processing device, so that the program code, when executed by the processor or controller, implements the functions/operations specified in the flow chart and/or block diagram.
  • the program code may be executed entirely on the machine, partially on the machine, partially on the machine and partially on a remote machine as a stand-alone software package, or entirely on a remote machine or server.
  • a machine-readable medium may be a tangible medium that may contain or store a program for use by or in conjunction with an instruction execution system, apparatus, or device.
  • a machine-readable medium may be a machine-readable signal medium or a machine-readable storage medium.
  • a machine-readable medium may include, but is not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing.
  • machine-readable storage media would include an electrical connection based on one or more wires, a portable computer disk, a hard disk, RAM, ROM, EPROM (Electrically Programmable Read-Only-Memory) or flash memory, optical fiber, CD-ROM (Compact Disc Read-Only Memory), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing.
  • the systems and techniques described herein may be implemented on a computer having: a display device (e.g., a CRT (Cathode-Ray Tube) or LCD (Liquid Crystal Display) monitor) for displaying information to the user; and a keyboard and pointing device (e.g., a mouse or trackball) through which the user can provide input to the computer.
  • a display device e.g., a CRT (Cathode-Ray Tube) or LCD (Liquid Crystal Display) monitor
  • a keyboard and pointing device e.g., a mouse or trackball
  • Other types of devices may also be used to provide interaction with the user; for example, the feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user may be received in any form (including acoustic input, voice input, or tactile input).
  • the systems and techniques described herein may be implemented in a computing system that includes backend components (e.g., as a data server), or a computing system that includes middleware components (e.g., an application server), or a computing system that includes frontend components (e.g., a user computer with a graphical user interface or a web browser through which a user can interact with implementations of the systems and techniques described herein), or a computing system that includes any combination of such backend components, middleware components, or frontend components.
  • the components of the system may be interconnected by any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include: LAN (Local Area Network), WAN (Wide Area Network), the Internet, and blockchain networks.
  • a computer system may include a client and a server.
  • the client and the server are generally remote from each other and usually interact through a communication network.
  • the relationship between the client and the server is generated by computer programs running on the corresponding computers and having a client-server relationship with each other.
  • the server may be a cloud server, also known as a cloud computing server or a cloud host, which is a host product in the cloud computing service system to solve the defects of difficult management and weak business scalability in traditional physical hosts and VPS services ("Virtual Private Server", or "VPS" for short).
  • the server may also be a server for a distributed system, or a server combined with a blockchain.
  • artificial intelligence is a discipline that studies how computers can simulate certain human thought processes and intelligent behaviors (such as learning, reasoning, thinking, planning, etc.), and includes both hardware-level and software-level technologies.
  • Artificial intelligence hardware technologies generally include technologies such as sensors, dedicated artificial intelligence chips, cloud computing, distributed storage, and big data processing; artificial intelligence software technologies mainly include computer vision technology, speech recognition technology, natural language processing technology, as well as machine learning/deep learning, big data processing technology, knowledge graph technology, and other major directions.

Landscapes

  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

一种磁珠检测的方法、装置及磁珠检测光学系统，利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；基于轮廓光源照亮待检测磁珠样本，产生磁珠的轮廓光信号；获取与荧光信号对应的第一光学图像信息；获取与轮廓光信号对应的第二光学图像信息；结合第一光学图像信息及第二光学图像信息，确定磁珠的种类及浓度分布。通过获取待检测样本的荧光信号与轮廓光信号进行成像，识别蛋白的种类与浓度能够实现对不同浓度、种类的待检测蛋白样本进行检测，进而提高样品的检测效率。

Description

磁珠检测的方法、装置及磁珠检测光学系统 技术领域
本公开涉及生物技术领域，尤其涉及一种磁珠检测的方法、装置及磁珠检测光学系统。
背景技术
目前，进行蛋白检验的主流技术是化学发光，化学发光技术具有灵敏度高，可自动化、灵活配置的优势，该技术已经逐渐取代了传统的胶体金、酶免荧光检测等方法。但是由于化学发光技术只能进行定量检测，想要实现多种标志物和极少样品的同时检测，需要进行分类检测；而分类检测的效率低，耗时长，从而导致时间成本和耗材成本变高，对于多种蛋白和不同浓度的样本需在较短的时间内得到检测结果的需求无法做到快速及时响应。
发明内容
本公开提供了一种磁珠检测的方法、装置及磁珠检测光学系统。其主要目的在于实现不同种类、浓度的蛋白联合检测。
根据本公开的第一方面，提供了一种磁珠检测光学系统，其中，包括：轮廓光源模块、激发光源模块以及成像模块；
所述轮廓光源模块，用于出射检测光至具有磁珠的待检测样本并照亮所述磁珠的轮廓产生轮廓光信号；
所述激发光源模块，用于出射激光至所述待检测样本，以激发所述磁珠产生荧光信号；
所述成像模块，包含光引导件及图像采集装置，其中，
所述光引导件位于所述待检测样本与所述图像采集装置之间，用于将所述轮廓光信号与所述荧光信号先后传递引导至所述图像采集装置；
所述图像采集装置获取与所述轮廓光信号对应的第一光学图像、以及与所述荧光信号对应的第二光学图像。
可选的，所述光引导件为第一二向色镜，所述第一二向色镜透射位于所述待检测样本与所述激发光源模块之间，所述激发光源模块产生的所述激光由所述第一二向色镜透射至所述待检测样本，所述荧光信号由所述第一二向色镜反射至所述图像采集装 置。
可选的，所述待检测样本位于所述第一二向色镜与所述轮廓光源模块之间，所述轮廓光源模块出射的所述检测光照亮所述磁珠产生的所述轮廓光信号由所述第一二向色镜反射至所述图像采集装置。
可选的，所述轮廓光源模块还包括：LED光源以及第二二向色镜；
所述LED光源，用于出射所述检测光至所述第二二向色镜；
所述第二二向色镜将所述检测光反射至所述待检测样本。
可选的，所述轮廓光模块还包括套设在所述LED光源外周并朝所述第二二向色镜延伸的反光环。
可选的，所述反光环为直径朝所述第二二向色镜方向增大的锥形筒状。
可选的，所述轮廓光模块还包括安装在所述反光环远离所述LED光源一侧的照明滤光片。
可选的，所述轮廓光模块还包括罩设在所述第二二向色镜背离所述LED光源一侧的消光罩。
可选的，所述激发光源模块包括激光器，所述激光器用于出射激光；所述第一二向色镜将所述激光透射至所述待检测样本。
可选的，所述激发光源模块还包括：反射镜；
所述反射镜，用于将所述激光器出射的所述激光反射至所述第一二向色镜。
可选的，所述图像采集装置包括图像传感器、以及位于所述图像传感器与所述光引导件之间的荧光滤光片；所述荧光滤光片对收集到的所述第一二向色镜传入的所述荧光信号进行过滤，并将过滤后的荧光信号入射至所述图像采集装置中。
可选的，所述图像采集装置还包括：位于所述光引导件与所述荧光滤光片之间的远心镜头。
可选的，所述系统还包括成像模块调节固定模块；
所述成像模块调节固定模块，包括第一二向色镜调节组件、镜头固定调节组件，用于固定所述成像模块以及调整成像角度。
可选的，所述系统还包括激发光源调节固定模块，包括光源固定座、光源调节座以及反光镜调节组件，用于固定所述激光器以及调整激光光路。
根据本公开的第二方面，提供了一种磁珠检测装置，包括本公开第一方面所述的磁珠检测光学系统。
可选的，所述装置还包括与成像模块连接的分析模块，所述分析模块接收第一光学图像及第二光学图像，并执行以下步骤：
根据所述第一光学图像识别所述待检测样本中的不同磁珠轮廓，并根据所述不同磁珠轮廓对所述待检测样本中的磁珠进行分类；
根据所述第二光学图像识别所待检测样本中不同浓度磁珠的荧光信号，根据所述荧光信号对所述磁珠的不同浓度进行定量检测；
结合磁珠轮廓及所述荧光灰度荧光信号，统计不同种类的磁珠的浓度分布。
根据本公开的第三方面，提供了一种磁珠检测的方法，包括：
利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；
基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号；
获取与所述荧光信号对应的第一光学图像信息；
获取与所述轮廓光信号对应的第二光学图像信息；
结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。
可选的，在利用激光照射待检测磁珠样本之前，所述方法还包括：
基于预选染料将所述待检测磁珠样本进行染色处理；其中，所述激光的波长不包括所述预选染料的荧光发射图谱。
可选的，在利用激光照射待检测磁珠样本之后，所述方法还包括：
利用消光罩将透过所述待检测磁珠样本的所述激光做消除背景光处理。
可选的，所述基于轮廓光源照亮所述待检测磁珠样本包括：
将所述轮廓光源产生的检测光进行均直化处理；
利用均直化处理后的照明光经二向色镜反射后照亮所述待检测磁珠样本，所述磁珠的轮廓信息；其中，所述照明光的波段包含所述待检测磁珠样本被激发的荧光激发谱。
可选的，所述获取与所述荧光信号对应的第一光学图像信息包括：
基于二向色镜，将所述荧光信号反射到图像采集装置内；
根据图像采集装置获得所述待检测磁珠样本对应的所述第一光学图像。
可选的，所述获取与所述轮廓光信号对应的第二光学图像信息包括：
基于二向色镜，将所述轮廓光信号反射到图像采集装置内；
根据图像采集装置获得所述待检测磁珠样本对应的所述第二光学图像。
根据本公开的第四方面，提供了一种电子设备，包括：
至少一个处理器；以及
与所述至少一个处理器通信连接的存储器；其中，
所述存储器存储有可被所述至少一个处理器执行的指令，所述指令被所述至少一个处理器执行，以使所述至少一个处理器能够执行前述第三方面所述的方法。
根据本公开的第五方面，提供了一种存储有计算机指令的非瞬时计算机可读存储介质，其中，所述计算机指令用于使所述计算机执行前述第三方面所述的方法。
根据本公开的第六方面，提供了一种计算机程序产品，包括计算机程序，所述计算机程序在被处理器执行时实现如前述第三方面所述的方法。
本公开提供一种磁珠检测的方法、装置及磁珠检测光学系统，利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号；获取与所述荧光信号对应的第一光学图像信息；获取与所述轮廓光信号对应的第二光学图像信息；结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。与相关技术相比，本公开实施例通过获取待检测样本的荧光信号与轮廓光信号进行成像，识别蛋白的种类与浓度；能够实现对不同浓度、种类的待检测蛋白样本进行检测，进而提升样品的检测效率。
应当理解，本部分所描述的内容并非旨在标识本申请的实施例的关键或重要特征，也不用于限制本申请的范围。本申请的其它特征将通过以下的说明书而变得容易理解。
附图说明
附图用于更好地理解本方案，不构成对本公开的限定。其中：
图1为本公开实施例提供的一种磁珠检测光学系统示意图；
图2为本公开实施例提供的一种磁珠检测光学系统的光路示意图；
图3为本公开实施例采用图1所示磁珠检测光学系统检测时沿A-A线的剖面图；
图4为图3所示磁珠检测光学系统中的轮廓光源模块的结构示意图；
图5为本公开实施例提供的一种图像采集装置的结构示意图；
图6为本公开实施例提供的一种磁珠检测光学系统另一视角的示意图；
图7为图6所示磁珠检测光学系统的部分P部放大示意图；
图8为本公开实施例提供的一种反光镜调节组件结构示意图；
图9为图8所示反光镜调节组件的分解示意图；
图10为本公开实施例提供的一种磁珠检测的装置的结构示意图；
图11为本公开实施例提供的一种磁珠检测的方法的流程示意图；
图12为本公开实施例提供的示例电子设备400的示意性框图。
具体实施方式
以下结合附图对本公开的示范性实施例做出说明，其中包括本公开实施例的各种细节以助于理解，应当将它们认为仅仅是示范性的。因此，本领域普通技术人员应当认识到，可以对这里描述的实施例做出各种改变和修改，而不会背离本公开的范围和精神。同样，为了清楚和简明，以下的描述中省略了对公知功能和结构的描述。
下面参考附图描述本公开实施例的磁珠检测的方法、装置及磁珠检测光学系统。
图1为本公开实施例所提供的一种磁珠检测光学系统示意图。如图1所示，所述蛋白联检的装置，包括：轮廓光源模块11、激发光源模块12以及成像模块13。应当理解，本申请所述“磁珠”可以为编码微球，其可以是具有细小粒径的超顺磁微球，和/或具有金属粒子的微球(其可在外加磁场作用下产生磁性)，磁珠的形状不限，可以是不规则形状，根据在轮廓光下获得的图像中的轮廓信息可以识别磁珠的种类于球形。
所述轮廓光源模块11，用于出射检测光至具有磁珠的待检测样本并照亮所述磁珠的轮廓产生轮廓光信号。
具体在本公开实施例中，如图1所示，轮廓光源模块11设置于待检测样本的上方。需要说明的是，轮廓光源模块11用于为待检测样本提供光源，能够实现轮廓光源模块11射出的光线照射到待检测样本即可，本公开实施例并不限制轮廓光源模块11的安装位置，例如：轮廓光源模块11同样的也可以安装于待检测样本的下方。前述说明仅仅是示范性的，并不构成对本公开的限定。
所述激发光源模块12，用于出射激光至所述待检测样本，以激发所述磁珠样本产生荧光信号。
请继续参阅图1，激发光源模块12设置于待检测磁珠样本的下方，激发光源模块12用于产生激光、并照射待检测样本产生荧光；激发光源模块12的激发光源的波长与携带染料的待检测磁珠样本荧光激发谱匹配，同时远离染料的荧光发射谱，所述染料根据激发光源模块12产生的激光的波长预先选定的。
结合图1-3所示，所述成像模块13，包含光引导件131及图像采集装置132，其中，所述光引导件131位于所述待检测样本与所述图像采集装置132之间，用于将所述轮廓光信号与所述荧光信号先后传递引导至所述图像采集装置132。
所述图像采集装置132获取与所述轮廓光信号对应的第一光学图像、以及与所述荧光信号对应的第二光学图像。
轮廓光源模块11要想能够实现照亮待检测磁珠样本的轮廓，轮廓光源模块11产生的光源的波段需要包含待检测磁珠样本被激发出的荧光的波段。光引导件131可以透过激发光源模块12产生的激发光源，激发光源照射待检测磁珠样本激发产生荧光， 光引导件131将轮廓光源模块11照射待检测磁珠样本产生的磁珠轮廓与被激发产生的荧光反射到图像采集装置132中。
本公开提供一种磁珠检测光学系统，利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号；获取与所述荧光信号对应的第一光学图像信息；获取与所述轮廓光信号对应的第二光学图像信息；结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。与相关技术相比，本公开实施例通过获取待检测样本的荧光信号与轮廓光信号进行成像，可以用于识别具有对应磁珠的蛋白的种类与浓度；能够实现对不同浓度、种类的蛋白样本进行检测，进而提升样品的检测效率。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述光引导件131为第一二向色镜1311，所述第一二向色镜1311透射位于所述待检测样本20与所述激发光源模块12之间，所述激发光源模块12产生的所述激光由所述第一二向色镜1311透射至所述待检测样本20，所述荧光信号由所述第一二向色镜1311反射至所述图像采集装置132。
具体在本公开实施例中，如图3所示，图3为采用图1所示磁珠检测光学系统对待检测样本20进行检测时沿A-A线的剖面图。第一二向色镜1311将激发光源模块12产生的激光透射至待检测样本20，第一二向色镜1311再将产生的荧光信号反射至图像采集装置132。第一二向色镜1311的位置可调，以实现对光路的可调；从而使得激发光源模块12产生的激光能更好的照亮待检测样本20中的磁珠，以产生荧光信号，并且将荧光信号反射至图像采集装置132。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述待检测样本20位于所述第一二向色镜1311与所述轮廓光源模块11之间，所述轮廓光源模块11出射的所述检测光照亮所述磁珠产生的所述轮廓光信号由所述第一二向色镜1311反射至所述图像采集装置132。
具体在本公开实施例中，请参阅图3，轮廓光源模块11出射的检测光将待检测样本20中的磁珠的轮廓照亮后，第一二向色镜1311将轮廓光信号反射至图像采集装置132。需要说明的是，轮廓光源模块11产生的检测光的波段不能透过第一二向色镜1311，而激发光源模块12产生的激光可以透过第一二向色镜1311。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述轮廓光源模块11还包括：LED光源111以及第二二向色镜112；所述LED光源111，用于出射所述检 测光至所述第二二向色镜112；所述第二二向色镜112将所述检测光反射至所述待检测样本20。
具体在本公开实施例中，请参阅图4，图4为本公开实施例提供的一种轮廓光源模块的结构示意图。轮廓光源模块11由LED光源111产生检测光，再由第二二向色镜112将检测光反射至待检测样本20，以照亮待检测样本20中的磁珠轮廓产生轮廓光信号。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述轮廓光源模块11还包括套设在所述LED光源111外周并朝所述第二二向色镜112延伸的反光环113。所述反光环113为直径朝所述第二二向色镜112方向增大的锥形筒状。在本申请的其他实施例中，也可以采用例如激光透镜替代反光环113，只要替换反光环的部件能产生聚光匀光效果即可。
具体在本公开实施例中，请参阅图4，在LED光源111的外周设置向第二二向色镜112延伸的增大的锥形筒状反光环113。反光环113将LED光源111产生的检测光进行均直化处理，来提高光线的利用率及照明的均匀性。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述轮廓光源模块11还包括安装在所述反光环113远离所述LED光源一侧的照明滤光片114。
具体在本公开实施例中，将检测光经过照明滤光片114过滤掉对检测有干扰的光线。需要说明的是，本公开实施例并不对使用何种类型的照明滤光片114进行限定。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述轮廓光源模块还包括罩设在所述第二二向色镜112背离所述LED光源111一侧的消光罩115。
具体在本公开实施例中，请参阅图3与图4，第二二向色镜112将LED光源111产生的检测光反射至待检测样本20；激发光源模块12产生的激光透射至待检测样本20后，会有部分激光穿过待检测样本20，射出至第二二向色镜112。第二二向色镜112将射出的激光透过后，激光射入消光罩115中；消光罩115具有吸光特性表面进行多次反射吸收，使得返回到待检测样本20的激光大幅降低，降低成像本底背景，同时还能有效收集激光，避免杂散光。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述激发光源模块12包括激光器121、反射镜122，所述激光器121用于出射激光；所述第一二向色镜1311将所述激光透射至所述待检测样本20。所述反射镜122，用于将所述激光器出射的所述激光反射至所述第一二向色镜1311。
具体在本公开实施例中，激光器121将射出的激光照射至反射镜122后，反射镜122将激光反射至第一二向色镜1311，激光透射过第一二向色镜1311后将待检测样本20中的磁珠激发出荧光。应当理解，在本发明的其他实施例中，也可以直接将激光器121正对待检测样本20入射激光激发磁珠，无需设置反射镜。
进一步地，在本实施例一种可能的实现方式中，如图2所示，所述图像采集装置132包括图像传感器1321、以及位于所述图像传感器1321与所述光引导件131之间的荧光滤光片1322；所述荧光滤光片1322对收集到的所述第一二向色镜1311传入的所述荧光信号进行过滤，并将过滤后的荧光信号入射至所述图像采集装置132中。优选地，所述图像采集装置132还包括：位于所述光引导件131与所述荧光滤光片之间的远心镜头1323。应当理解，在本发明的其他实施例中，也可以选用其他可达到分辨要求和视场要求的工业镜头替换远心镜头。
具体在本公开实施例中，如图5所示，图5为本公开实施例提供的一种图像采集装置的结构示意图。荧光信号与轮廓光信号先经由第一二向色镜1311传入远心镜头1323。在本公开的一些可实现的方式中，选择大视场远心镜头，可以使得成像视场大，能够匹配所选检测板单孔大小进行一次或多次拍照，单次拍照面积越大，单孔所需拍照次数越小，检测效率越高，检测成本越低。荧光信号与轮廓光信号再经由远心镜头1323传入荧光滤光片1322，由荧光滤光片1322对荧光信号与轮廓光信号中的激光与环境光等杂乱光线进行过滤，以降低对成像结果的影响。在经过荧光滤光片1322的滤光处理后，由图像传感器1321获取荧光信号与轮廓光信号，并将荧光信号与轮廓光信号转换成对应的图像信息。
进一步地，在本实施例一种可能的实现方式中，如图6所示，所述系统还包括成像模块调节固定模块；
所述成像模块调节固定模块14，包括第一二向色镜调节组件141、镜头固定调节组件142，用于固定所述成像模块13以及调整成像角度。
具体在本公开实施例中，第一二向色镜调节组件141主要保证第一二向色镜安装角度符合45度入射，并尽可能的保证光轴的位置与理想的光轴一致。镜头固定调节组件142主要起到固定整个成像系统位置的作用；同时，还可以对整个成像模块13进行XYZ三个方向的位置调节，同时可对成像系统的倾斜和俯仰角度进行调节，以实现整个成像光路的光轴与经第一二向色镜1311反射的照明系统的光轴重合；从而实现检测板上的磁珠孔能落在检测系统的调焦范围内。
进一步地，在本实施例一种可能的实现方式中，如图6-7所示，所述系统还包括激发光源调节固定模块15，包括光源固定座151、光源调节座152以及反光镜调节组件153，用于固定所述激光器121以及调整激光光路。
具体在本公开实施例中，利用光源固定座151将激光器121固定、光源调节座152主要用于对激光光线的出射角度进行调节。如图8-9所示，在本公开实施例提供的一种反光镜调节组件中，反光镜调节组件153由反光镜固定框1531，调节座1532，及遮光盖板1533组成。反光镜调节组件153主要保证反射镜122安装角度符合45度入射，并尽可能的保证光轴的位置与理想的光轴一致。
图10为本公开实施例提供的一种磁珠检测的装置的结构示意图，所述装置包括：磁珠检测光学系统21、分析模块22。
进一步地，在本实施例一种可能的实现方式中，如图9所示，所述装置还包括与成像模块连接的分析模块22，所述分析模块22接收第一光学图像及第二光学图像，并执行以下步骤：
根据所述第一光学图像识别所述待检测样本20中的不同磁珠轮廓，并根据所述不同磁珠轮廓对所述待检测样本20中的磁珠进行分类；
根据所述第二光学图像识别所待检测样本20中不同浓度磁珠的荧光信号，根据所述荧光信号对所述磁珠的不同浓度进行定量检测；
结合磁珠轮廓及所述荧光灰度荧光信号，统计不同种类的磁珠的浓度分布。
与上述的磁珠检测的装置相对应，本发明还提出一种磁珠检测的方法。由于本发明的装置实施例与上述的方法实施例相对应，对于装置实施例中未披露的细节可参照上述的方法实施例，本发明中不再进行赘述。
图11为本公开实施例提供的一种磁珠检测的方法的流程示意图。
如图11所示，该方法包含以下步骤：
步骤301，利用激光照射待检测磁珠样本，激发磁珠产生荧光信号。
通过激发光源模块产生的激光，照射待检测磁珠样本产生荧光；激发光源模块的激发光源的波长与待检测磁珠样本携带染料的荧光激发谱匹配，同时远离染料的荧光发射谱。
步骤302，获取与所述荧光信号对应的第一光学图像信息。
步骤301’，基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号。
利用轮廓光源，从磁珠的轮廓可以进一步分辨出与磁珠偶联的蛋白的种类。通过 轮廓光源模块为待检测磁珠样本提供光源，能够实现对待检测磁珠样本进行照射，进而获取到磁珠的轮廓光信号。
磁珠检测的装置通过将得到的荧光传入成像模块，获取到关于待检测磁珠样本的第一光学图像信息。
步骤302’，获取与所述轮廓光信号对应的第二光学图像信息。
磁珠检测的装置通过将得到的轮廓传入成像模块，获取到关于待检测磁珠样本的第二光学图像信息。
步骤303，结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。
应当理解，上述第一光学图像信息与第二光学图像信息的获取先后顺序不做限定，例如可以先对待检测样本照射轮廓光获取第二光学图像信息，再挂你轮廓光开启激光光源获取第一光学图像信息。
磁珠的轮廓可以表征与磁珠结合的蛋白的种类，荧光的亮度可以表征磁珠的浓度分布。根据图像信息中反应的荧光与轮廓的信息，进一步确定磁珠的种类以及浓度的分布。
本公开提供一种磁珠检测的方法，利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号；获取与所述荧光信号对应的第一光学图像信息；获取与所述轮廓光信号对应的第二光学图像信息；结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。与相关技术相比，本公开实施例通过获取待检测样本的荧光信号与轮廓光信号进行成像，识别蛋白的种类与浓度；能够实现对不同浓度、种类的待检测蛋白样本进行检测，进而提升样品的检测效率。
作为本公开的一种可行的方式，在利用激光照射待检测磁珠样本之前，所述方法还包括：
基于预选染料将所述待检测磁珠样本进行染色处理；其中，所述激光的波长不包括所述预选染料的荧光发射图谱。
在本公开实施例中，在进行磁珠检测时，需要对待检测磁珠样本进行染色处理。染料的荧光激发谱与激发光源的波长相匹配，同时激发光源的波长要远离染料的荧光发射谱。
作为本公开的一种可行的方式，在利用激光照射待检测磁珠样本之后，所述方法还包括：
利用消光罩将透过所述待检测磁珠样本的所述激光做消除背景光处理。
透过待检测磁珠样本后的激光，会在磁珠检测的装置内被反射返回原来的光路中，影响实验的结果，因此需要将透过待检测磁珠样本的激光进行消光处理。激光经过消光罩内的反射镜反射至其内部，在消光罩内表面由具有吸光特性的材料制成，通过多次反射吸收。避免杂散光对实验的干扰以及激光射出装置外发生意外。
作为本公开的一种可行的方式，所述基于轮廓光源照亮所述待检测磁珠样本包括：
将所述轮廓光源产生的检测光进行均直化处理；
利用均直化处理后的照明光经二向色镜反射后照亮所述待检测磁珠样本，所述磁珠的轮廓信息；其中，所述照明光的波段包含所述待检测磁珠样本被激发的荧光激发谱。
利用聚光器件(包括但不限于聚光透镜或者反光环)对轮廓光源进行均直化处理，来提高光线的利用率及照明的均匀性。将轮廓光源经过照明滤光片过滤掉对检测有干扰的光线。轮廓光源经第二二向色镜反射后，照亮待检测磁珠样本的轮廓；轮廓光源要想能够实现照亮待检测磁珠样本的轮廓，轮廓光源的波段需要包含待检测磁珠样本被激发出的荧光的波段。
作为本公开的一种可行的方式，所述获取与所述荧光信号对应的第一光学图像信息包括：
基于二向色镜，将所述荧光信号反射到图像采集装置内；
根据图像采集装置获得所述待检测磁珠样本对应的所述第一光学信息。
在本公开实施例中，利用二向色镜透射激光，激光照射待检测磁珠样本激发产生荧光，二向色镜将被激发产生的荧光反射到图像采集装置中。图像采集装置将第一光学信息输出至计算机设备，由计算机设备进一步确定磁珠的种类以及浓度的分布。
作为本公开的一种可行的方式，所述获取与所述轮廓光信号对应的第二光学图像信息包括：
基于二向色镜，将所述轮廓光信号反射到图像采集装置内；
根据图像采集装置获得所述待检测磁珠样本对应的所述第二光学图像。
在本公开实施例中，利用二向色镜反射检测光，检测光照射待检测磁珠样本产生轮廓光信号，二向色镜将轮廓光源照射待检测磁珠样本产生的轮廓光信号反射到图像采集装置中。图像采集装置将第二光学信息输出至计算机设备，由计算机设备进一步确定磁珠的种类以及浓度的分布。
需要说明的是，前述对方法实施例的解释说明，也适用于本实施例的装置，原理相同，本实施例中不再限定。
根据本公开的实施例，本公开还提供了一种电子设备、一种可读存储介质和一种计算机程序产品。
图12示出了可以用来实施本公开的实施例的示例电子设备400的示意性框图。电子设备旨在表示各种形式的数字计算机，诸如，膝上型计算机、台式计算机、工作台、个人数字助理、服务器、刀片式服务器、大型计算机、和其它适合的计算机。电子设备还可以表示各种形式的移动装置，诸如，个人数字处理、蜂窝电话、智能电话、可穿戴设备和其它类似的计算装置。本文所示的部件、它们的连接和关系、以及它们的功能仅仅作为示例，并且不意在限制本文中描述的和/或者要求的本公开的实现。
如图12所示，设备400包括计算单元401，其可以根据存储在ROM(Read-Only Memory，只读存储器)402中的计算机程序或者从存储单元408加载到RAM(Random Access Memory，随机访问/存取存储器)403中的计算机程序，来执行各种适当的动作和处理。在RAM 403中，还可存储设备400操作所需的各种程序和数据。计算单元401、ROM 402以及RAM 403通过总线404彼此相连。I/O(Input/Output，输入/输出)接口405也连接至总线404。
设备400中的多个部件连接至I/O接口405，包括：输入单元406，例如键盘、鼠标等；输出单元407，例如各种类型的显示器、扬声器等；存储单元408，例如磁盘、光盘等；以及通信单元409，例如网卡、调制解调器、无线通信收发机等。通信单元409允许设备400通过诸如因特网的计算机网络和/或各种电信网络与其他设备交换信息/数据。
计算单元401可以是各种具有处理和计算能力的通用和/或专用处理组件。计算单元401的一些示例包括但不限于CPU(Central Processing Unit，中央处理单元)、GPU(Graphic Processing Units，图形处理单元)、各种专用的AI(Artificial Intelligence，人工智能)计算芯片、各种运行机器学习模型算法的计算单元、DSP(Digital Signal Processor，数字信号处理器)、以及任何适当的处理器、控制器、微控制器等。计算单元401执行上文所描述的各个方法和处理，例如磁珠检测的方法。例如，在一些实施例中，磁珠检测的方法可被实现为计算机软件程序，其被有形地包含于机器可读介质，例如存储单元408。在一些实施例中，计算机程序的部分或者全部可以经由ROM 402和/或通信单元409而被载入和/或安装到设备400上。当计算机程序加载到RAM 403并由计算单元401执行时，可以执行上文描述的方法的一个或多个步骤。备选地，在其他实施例中，计算单元401可以通过其他任何适当的方式(例如，借助于固件)而被配置为执行前述磁珠检测的方法。
本文中以上描述的系统和技术的各种实施方式可以在数字电子电路系统、集成电路系统、FPGA(Field Programmable Gate Array，现场可编程门阵列)、ASIC(Application-Specific Integrated Circuit，专用集成电路)、ASSP(Application Specific Standard Product，专用标准产品)、SOC(System On Chip，芯片上系统的系统)、CPLD(Complex Programmable Logic Device，复杂可编程逻辑设备)、计算机硬件、固件、软件、和/或它们的组合中实现。这些各种实施方式可以包括：实施在一个或者多个计算机程序中，该一个或者多个计算机程序可在包括至少一个可编程 处理器的可编程系统上执行和/或解释，该可编程处理器可以是专用或者通用可编程处理器，可以从存储系统、至少一个输入装置、和至少一个输出装置接收数据和指令，并且将数据和指令传输至该存储系统、该至少一个输入装置、和该至少一个输出装置。
用于实施本公开的方法的程序代码可以采用一个或多个编程语言的任何组合来编写。这些程序代码可以提供给通用计算机、专用计算机或其他可编程数据处理装置的处理器或控制器，使得程序代码当由处理器或控制器执行时使流程图和/或框图中所规定的功能/操作被实施。程序代码可以完全在机器上执行、部分地在机器上执行，作为独立软件包部分地在机器上执行且部分地在远程机器上执行或完全在远程机器或服务器上执行。
在本公开的上下文中，机器可读介质可以是有形的介质，其可以包含或存储以供指令执行系统、装置或设备使用或与指令执行系统、装置或设备结合地使用的程序。机器可读介质可以是机器可读信号介质或机器可读储存介质。机器可读介质可以包括但不限于电子的、磁性的、光学的、电磁的、红外的、或半导体系统、装置或设备，或者上述内容的任何合适组合。机器可读存储介质的更具体示例会包括基于一个或多个线的电气连接、便携式计算机盘、硬盘、RAM、ROM、EPROM(Electrically Programmable Read-Only-Memory，可擦除可编程只读存储器)或快闪存储器、光纤、CD-ROM(Compact Disc Read-Only Memory，便捷式紧凑盘只读存储器)、光学储存设备、磁储存设备、或上述内容的任何合适组合。
为了提供与用户的交互，可以在计算机上实施此处描述的系统和技术，该计算机具有：用于向用户显示信息的显示装置(例如，CRT(Cathode-Ray Tube，阴极射线管)或者LCD(LiquidCrystal Display，液晶显示器)监视器)；以及键盘和指向装置(例如，鼠标或者轨迹球)，用户可以通过该键盘和该指向装置来将输入提供给计算机。其它种类的装置还可以用于提供与用户的交互；例如，提供给用户的反馈可以是任何形式的传感反馈(例如，视觉反馈、听觉反馈、或者触觉反馈)；并且可以用任何形式(包括声输入、语音输入或者、触觉输入)来接收来自用户的输入。
可以将此处描述的系统和技术实施在包括后台部件的计算系统(例如，作为数据服务器)、或者包括中间件部件的计算系统(例如，应用服务器)、或者包括前端部件的计算系统(例如，具有图形用户界面或者网络浏览器的用户计算机，用户可以通过该图形用户界面或者该网络浏览器来与此处描述的系统和技术的实施方式交互)、或者包括这种后台部件、中间件部件、或者前端部件的任何组合的计算系统中。可以通过任何形式或者介质的数字数据通信(例如，通信网络)来将系统的部件相互连接。通信网络的示例包括：LAN(Local Area Network，局域网)、WAN(Wide Area Network，广域网)、互联网和区块链网络。
计算机系统可以包括客户端和服务器。客户端和服务器一般远离彼此并且通常通过通信网络进行交互。通过在相应的计算机上运行并且彼此具有客户端-服务器关系的计算机程序来产生客户端和服务器的关系。服务器可以是云服务器，又称为云计算服 务器或云主机，是云计算服务体系中的一项主机产品，以解决了传统物理主机与VPS服务("Virtual Private Server"，或简称"VPS")中，存在的管理难度大，业务扩展性弱的缺陷。服务器也可以为分布式系统的服务器，或者是结合了区块链的服务器。
其中，需要说明的是，人工智能是研究使计算机来模拟人的某些思维过程和智能行为(如学习、推理、思考、规划等)的学科，既有硬件层面的技术也有软件层面的技术。人工智能硬件技术一般包括如传感器、专用人工智能芯片、云计算、分布式存储、大数据处理等技术；人工智能软件技术主要包括计算机视觉技术、语音识别技术、自然语言处理技术以及机器学习/深度学习、大数据处理技术、知识图谱技术等几大方向。
应该理解，可以使用上面所示的各种形式的流程，重新排序、增加或删除步骤。例如，本公开中记载的各步骤可以并行地执行也可以顺序地执行也可以不同的次序执行，只要能够实现本公开公开的技术方案所期望的结果，本文在此不进行限制。
上述具体实施方式，并不构成对本公开保护范围的限制。本领域技术人员应该明白的是，根据设计要求和其他因素，可以进行各种修改、组合、子组合和替代。任何在本公开的精神和原则之内所作的修改、等同替换和改进等，均应包含在本公开保护范围之内。

Claims (22)

  1. 一种磁珠检测光学系统，其特征在于，包括：轮廓光源模块、激发光源模块以及成像模块；
    所述轮廓光源模块，用于出射检测光至具有磁珠的待检测样本并照亮所述磁珠的轮廓产生轮廓光信号；
    所述激发光源模块，用于出射激光至所述待检测样本，以激发所述磁珠产生荧光信号；
    所述成像模块，包含光引导件及图像采集装置，其中，
    所述光引导件位于所述待检测样本与所述图像采集装置之间，用于将所述轮廓光信号与所述荧光信号先后传递引导至所述图像采集装置；
    所述图像采集装置获取与所述轮廓光信号对应的第一光学图像、以及与所述荧光信号对应的第二光学图像。
  2. 根据权利要求1所述的磁珠检测光学系统，其特征在于，所述光引导件为第一二向色镜，所述第一二向色镜透射位于所述待检测样本与所述激发光源模块之间，所述激发光源模块产生的所述激光由所述第一二向色镜透射至所述待检测样本，所述荧光信号由所述第一二向色镜反射至所述图像采集装置。
  3. 根据权利要求2所述的磁珠检测光学系统，其特征在于，所述待检测样本位于所述第一二向色镜与所述轮廓光源模块之间，所述轮廓光源模块出射的所述检测光照亮所述磁珠产生的所述轮廓光信号由所述第一二向色镜反射至所述图像采集装置。
  4. 根据权利要求3所述的磁珠检测光学系统，其特征在于，所述轮廓光源模块还包括：LED光源以及第二二向色镜；
    所述LED光源，用于出射所述检测光至所述第二二向色镜；
    所述第二二向色镜将所述检测光反射至所述待检测样本。
  5. 根据权利要求4所述的磁珠检测光学系统，其特征在于，所述轮廓光模块还包括套设在所述LED光源外周并朝所述第二二向色镜延伸的反光环。
  6. 根据权利要求5所述的磁珠检测光学系统，其特征在于，所述反光环为直径朝所述第二二向色镜方向增大的锥形筒状。
  7. 根据权利要求5所述的磁珠检测光学系统，其特征在于，所述轮廓光模块还包括安装在所述反光环远离所述LED光源一侧的照明滤光片。
  8. 根据权利要求4所述的磁珠检测光学系统，其特征在于，所述轮廓光模块还包括罩设在所述第二二向色镜背离所述LED光源一侧的消光罩。
  9. 根据权利要求2所述的磁珠检测光学系统，其特征在于，所述激发光源模块包括激光器，所述激光器用于出射激光；所述第一二向色镜将所述激光透射至所述待检测样本。
  10. 根据权利要求9所述的磁珠检测光学系统，其特征在于，所述激发光源模块还包括：反射镜；
    所述反射镜，用于将所述激光器出射的所述激光反射至所述第一二向色镜。
  11. 根据权利要求2所述的磁珠检测光学系统，其特征在于，所述图像采集装置包括图像传感器、以及位于所述图像传感器与所述光引导件之间的荧光滤光片；所述荧光滤光片对收集到的所述第一二向色镜传入的所述荧光信号进行过滤，并将过滤后的荧光信号入射至所述图像采集装置中。
  12. 根据权利要求11所述的磁珠检测光学系统，其特征在于，所述图像采集装置还包括：位于所述光引导件与所述荧光滤光片之间的远心镜头。
  13. 根据权利要求12所述的磁珠检测光学系统，其特征在于，所述系统还包括成像模块调节固定模块；
    所述成像模块调节固定模块，包括第一二向色镜调节组件、镜头固定调节组件，用于固定所述成像模块以及调整成像角度。
  14. 根据权利要求10所述的磁珠检测光学系统，其特征在于，所述系统还包括激发光源调节固定模块，包括光源固定座、光源调节座以及反光镜调节组件，用于固定所述激光器以及调整激光光路。
  15. 一种磁珠检测装置，其特征在于，包括如权利要求1-14任一项所述的磁珠检测光学系统。
  16. 根据权利要求15所述的磁珠检测装置，其特征在于，所述装置还包括与成像模块连接的分析模块，所述分析模块接收第一光学图像及第二光学图像，并执行以下步骤：
    根据所述第一光学图像识别所述待检测样本中的不同磁珠轮廓，并根据所述不同磁珠轮廓对所述待检测样本中的磁珠进行分类；
    根据所述第二光学图像识别所待检测样本中不同浓度磁珠的荧光信号，根据所述荧光信号对所述磁珠的不同浓度进行定量检测；
    结合磁珠轮廓及所述荧光灰度荧光信号，统计不同种类的磁珠的浓度分布。
  17. 一种磁珠检测的方法，其特征在于，包括：
    利用激光照射待检测磁珠样本，激发磁珠产生荧光信号；
    基于轮廓光源照亮所述待检测磁珠样本，产生所述磁珠的轮廓光信号；
    获取与所述荧光信号对应的第一光学图像信息；
    获取与所述轮廓光信号对应的第二光学图像信息；
    结合所述第一光学图像信息及所述第二光学图像信息，确定所述磁珠的种类及浓度分布。
  18. 根据权利要求17所述的方法，其特征在于，在利用激光照射待检测磁珠样本之前，所述方法还包括：
    基于预选染料将所述待检测磁珠样本进行染色处理；其中，所述激光的波长 不包括所述预选染料的荧光发射图谱。
  19. 根据权利要求17所述的方法，其特征在于，在利用激光照射待检测磁珠样本之后，所述方法还包括：
    利用消光罩将透过所述待检测磁珠样本的所述激光做消除背景光处理。
  20. 根据权利要求17所述的方法，其特征在于，所述基于轮廓光源照亮所述待检测磁珠样本包括：
    将所述轮廓光源产生的检测光进行均直化处理；
    利用均直化处理后的照明光经二向色镜反射后照亮所述待检测磁珠样本，所述磁珠的轮廓信息；其中，所述照明光的波段包含所述待检测磁珠样本被激发的荧光激发谱。
  21. 根据权利要求17所述的方法，其特征在于，所述获取与所述荧光信号对应的第一光学图像信息包括：
    基于二向色镜，将所述荧光信号反射到图像采集装置内；
    根据图像采集装置获得所述待检测磁珠样本对应的所述第一光学图像。
  22. 根据权利要求17所述的方法，其特征在于，所述获取与所述轮廓光信号对应的第二光学图像信息包括：
    基于二向色镜，将所述轮廓光信号反射到图像采集装置内；
    根据图像采集装置获得所述待检测磁珠样本对应的所述第二光学图像。
PCT/CN2022/134430 2022-11-25 2022-11-25 磁珠检测的方法、装置及磁珠检测光学系统 WO2024108569A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/134430 WO2024108569A1 (zh) 2022-11-25 2022-11-25 磁珠检测的方法、装置及磁珠检测光学系统

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/134430 WO2024108569A1 (zh) 2022-11-25 2022-11-25 磁珠检测的方法、装置及磁珠检测光学系统

Publications (1)

Publication Number Publication Date
WO2024108569A1 true WO2024108569A1 (zh) 2024-05-30

Family

ID=91195018

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/134430 WO2024108569A1 (zh) 2022-11-25 2022-11-25 磁珠检测的方法、装置及磁珠检测光学系统

Country Status (1)

Country Link
WO (1) WO2024108569A1 (zh)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030142291A1 (en) * 2000-08-02 2003-07-31 Aravind Padmanabhan Portable scattering and fluorescence cytometer
JP2006133499A (ja) * 2004-11-05 2006-05-25 Shimadzu Corp 共焦点スキャナ及び共焦点顕微鏡
US20060275891A1 (en) * 2005-06-03 2006-12-07 Hiroshi Kishida Apparatus and method for reading fluorescence from bead arrays
US20090237501A1 (en) * 2008-03-19 2009-09-24 Ruprecht-Karis-Universitat Heidelberg Kirchhoff-Institut Fur Physik method and an apparatus for localization of single dye molecules in the fluorescent microscopy
CN102023208A (zh) * 2009-09-15 2011-04-20 索尼公司 微珠分析方法和微珠分析器
JP2011191199A (ja) * 2010-03-15 2011-09-29 Japan Science & Technology Agency 顕微鏡システム
CN112129734A (zh) * 2020-08-28 2020-12-25 东北大学 一种深度可分辨荧光成像系统
CN113063766A (zh) * 2021-03-29 2021-07-02 新羿制造科技（北京）有限公司 含双凸透镜的微液滴荧光信号检测装置
WO2021135991A1 (zh) * 2019-12-31 2021-07-08 深圳市帝迈生物技术有限公司 实现分类和定量分析的检测系统、免疫多联检的检测方法
CN113376127A (zh) * 2020-02-25 2021-09-10 上海交通大学 一种适于生物分子多重检测的成像系统
CN114088678A (zh) * 2021-12-03 2022-02-25 嘉兴市唯真生物科技有限公司 一种流式荧光检测方法

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030142291A1 (en) * 2000-08-02 2003-07-31 Aravind Padmanabhan Portable scattering and fluorescence cytometer
JP2006133499A (ja) * 2004-11-05 2006-05-25 Shimadzu Corp 共焦点スキャナ及び共焦点顕微鏡
US20060275891A1 (en) * 2005-06-03 2006-12-07 Hiroshi Kishida Apparatus and method for reading fluorescence from bead arrays
US20090237501A1 (en) * 2008-03-19 2009-09-24 Ruprecht-Karis-Universitat Heidelberg Kirchhoff-Institut Fur Physik method and an apparatus for localization of single dye molecules in the fluorescent microscopy
CN102023208A (zh) * 2009-09-15 2011-04-20 索尼公司 微珠分析方法和微珠分析器
JP2011191199A (ja) * 2010-03-15 2011-09-29 Japan Science & Technology Agency 顕微鏡システム
WO2021135991A1 (zh) * 2019-12-31 2021-07-08 深圳市帝迈生物技术有限公司 实现分类和定量分析的检测系统、免疫多联检的检测方法
CN113376127A (zh) * 2020-02-25 2021-09-10 上海交通大学 一种适于生物分子多重检测的成像系统
CN112129734A (zh) * 2020-08-28 2020-12-25 东北大学 一种深度可分辨荧光成像系统
CN113063766A (zh) * 2021-03-29 2021-07-02 新羿制造科技（北京）有限公司 含双凸透镜的微液滴荧光信号检测装置
CN114088678A (zh) * 2021-12-03 2022-02-25 嘉兴市唯真生物科技有限公司 一种流式荧光检测方法

Similar Documents

Publication Publication Date Title
US20230296494A1 (en) Flow Cytometer With Optical Equalization
US10371639B2 (en) Detecting fluorescent material in a stained particle by comparison with an unstained particle over a plurality of frequency bands and by estimating a linear combination of base vectors
US9360410B2 (en) Method and particle analyzer for determining a broad particle size distribution
US9625370B2 (en) Microscope with spectroscopic capability
US20140320861A1 (en) Methods and systems for the collection of light using total internal reflectance
US11674905B2 (en) Fluorescence imaging of gemstone on transparent stage
JP2021510818A (ja) 動的な光検出抑制システムおよびこれを使用する方法
Kim et al. Volumetric monitoring of airborne particulate matter concentration using smartphone-based digital holographic microscopy and deep learning
CN211478007U (zh) 样本分析仪及其光学系统、流式细胞仪
WO2024108569A1 (zh) 磁珠检测的方法、装置及磁珠检测光学系统
US11346762B2 (en) Systems for dynamic light detection obscuration and methods for using thereof
JP2013542441A (ja) ナノ粒子検出器
CN115176139A (zh) 用于调整训练门以适应流式细胞仪数据的方法和系统
CN107389566A (zh) 一种用于光谱仪中收集样品漫反射光的装置
Algazinov et al. Methods of measuring the spectral characteristics and identifying the components of grain mixtures in real-time separation systems
CN109342394A (zh) 一种采用双波长激光的手持式拉曼光谱仪及实现方法
CN205449805U (zh) 一种表面增强拉曼光谱测试系统
US9562862B2 (en) Optical and chemical analytical systems and methods
WO2019237242A1 (zh) 一种检测系统及信号增强装置
US20220107260A1 (en) Method for processing and displaying multi-channel spectral histograms and systems for same
US20220155210A1 (en) Flow Cytometer Including Light Collection Modules, and Methods of Using The Same
Anthony et al. PWSpy: A Python library dedicated to the analysis of Partial Wave Spectroscopic Microscopy data.
US20220065792A1 (en) A system and a method of performing spectroscopic analysis of a sample
Kochelaev et al. Optical recording system for a flow-through optical method of analyzing bioaerosols
JP2023549475A (ja) 傾斜ビーム成形光学部品を含むフローサイトメータ、及びフローサイトメータを使用する方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22966257

Country of ref document: EP

Kind code of ref document: A1