WO2022226868A1 - 芯片装载结构、分析装置及分析系统 - Google Patents

芯片装载结构、分析装置及分析系统 Download PDF

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Publication number
WO2022226868A1
WO2022226868A1 PCT/CN2021/090878 CN2021090878W WO2022226868A1 WO 2022226868 A1 WO2022226868 A1 WO 2022226868A1 CN 2021090878 W CN2021090878 W CN 2021090878W WO 2022226868 A1 WO2022226868 A1 WO 2022226868A1
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Prior art keywords
chip
loading
detection chip
board surface
detection
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Application number
PCT/CN2021/090878
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English (en)
French (fr)
Inventor
侯孟军
马相国
耿凯
吴琼
王友学
刘宗民
Original Assignee
京东方科技集团股份有限公司
北京京东方技术开发有限公司
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Application filed by 京东方科技集团股份有限公司, 北京京东方技术开发有限公司 filed Critical 京东方科技集团股份有限公司
Priority to US17/638,885 priority Critical patent/US20240042431A1/en
Priority to CN202180000986.0A priority patent/CN115735005A/zh
Priority to PCT/CN2021/090878 priority patent/WO2022226868A1/zh
Publication of WO2022226868A1 publication Critical patent/WO2022226868A1/zh

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/36Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/42Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/143Quality control, feedback systems
    • B01L2200/147Employing temperature sensors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/025Displaying results or values with integrated means
    • B01L2300/027Digital display, e.g. LCD, LED
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0654Lenses; Optical fibres
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0819Microarrays; Biochips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0829Multi-well plates; Microtitration plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1838Means for temperature control using fluid heat transfer medium
    • B01L2300/1844Means for temperature control using fluid heat transfer medium using fans
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1894Cooling means; Cryo cooling
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Definitions

  • Embodiments of the present disclosure relate to a chip loading structure, an analysis device, and an analysis system.
  • dPCR Digital polymerase chain reaction chip technology Due to its high sensitivity, strong specificity, high detection throughput, and accurate quantification, it has been widely used in clinical diagnosis, gene instability analysis, single-cell gene expression, environmental microbial detection, and prenatal diagnosis.
  • At least one embodiment of the present disclosure provides a chip loading structure, which includes a loading board body, and the loading board body has an accommodating space for accommodating a detection chip;
  • a first hollowed-out area and at least one second hollowed-out area are arranged on the first plate surface of the loading plate body, and at least one second hollowed-out area penetrates through the accommodating space, wherein the first hollowed-out area is used for exposing the reaction of the detection chip an observation area; at least one of the second hollow areas is used to expose at least one reagent port of the detection chip;
  • the loading plate body is further provided with a connecting portion, and the connecting portion can be detachably connected with the transporting portion in the analysis device for transporting the loading plate body.
  • a first concave portion is provided on the first board surface and at the position where the first hollow area is located, and the orthographic projection area of the first concave portion on the first board surface is greater than The orthographic projection area of the first hollow area on the first board surface, and the orthographic projection of the first recessed portion on the first board surface completely covers the first hollow area on the first board surface. Orthographic projection on the board.
  • the shape of the orthographic projection of the first hollow area on the first board surface includes a square, a rectangle or a circle.
  • a plurality of the second hollow areas are arranged at intervals along a first axis of the first board surface, and the first axis is when the loading board body is placed on the transport portion.
  • the direction is parallel to the first movement direction of the transport part moving into the analysis device.
  • a second concave portion is provided on the first board surface and at the position of each of the second hollow areas, and the second concave portion is on the positive side of the first board surface.
  • the projected area is greater than the orthographic projection area of the second hollow area on the first board surface, and the orthographic projection of the second recessed portion on the first board surface completely covers where the second hollow area is located. Describe the orthographic projection on the first board.
  • the orthographic projection area of the second concave part behind in the first moving direction on the first plate surface is greater than an orthographic projection area of the second recessed portion forward in the first moving direction on the first board surface;
  • the orthographic projection of the second concave portion at the back in the first moving direction on the first plate surface is an oblong hole; the second concave portion at the front in the first moving direction is at The orthographic projection on the first plate surface is a circular hole.
  • the detection chip further has a heating electrode; and a third hollow area extending through the accommodating space is provided on the first board surface for exposing the heating electrode.
  • the third hollow area extends to the first side of the first board surface
  • the first side edge and the first axis of the first board surface are perpendicular to each other; the direction of the first axis when the loading board body is placed on the transport part is the same as the movement of the transport part
  • the first moving directions inside the analysis device are parallel to each other, and the first side is the front side in the first moving direction.
  • an accommodating groove is provided on the second board surface of the loading board body that is away from the first board surface, so as to form the accommodating space, and an inner side surface of the accommodating groove is provided.
  • a protruding structure is provided to define the detection chip in the accommodating groove.
  • the protruding structure includes two sets of protruding part groups distributed on both sides of the first axis of the first board surface, and each group of the protruding part sets includes a plurality of protruding part groups distributed along the first axis at intervals.
  • Each of the protruding portions protrudes from the inner side of the accommodating groove toward the direction close to the first axis, so as to abut against the side surface of the detection chip placed in the accommodating groove ;
  • the direction of the first axis when the loading plate body is placed on the conveying part is parallel to the first moving direction of the conveying part moving into the analysis device.
  • an orthographic projection shape of the convex portion on the second plate surface includes an arc shape.
  • the accommodating groove extends to the second side of the second board surface
  • the second side is perpendicular to the first axis of the first board surface; the direction of the first axis when the loading board is placed on the transport portion is the same as when the transport portion moves in.
  • the first moving directions inside the analysis device are parallel to each other, and the second side is the side that is forward in the first moving direction.
  • two side surfaces of the loading body located on both sides of the first axis of the first plate surface are respectively provided with slot groups, and each group of the slot groups includes a a plurality of slots spaced by the first axis, the slots are used as the connecting part to be inserted with the connectors in the transport part in a one-to-one correspondence; the first axis is in the loading plate body The direction when placed on the conveying part is parallel to the first moving direction of the conveying part moving into the analysis device.
  • a socket communicated with the slot is provided on the second board surface of the loading board body that is away from the first board surface, so that the corresponding plug-in connector can be moved into or out of the socket.
  • the plug connector On the side surface of the slot located on the side of the second axis, there is a limiting convex part protruding in the direction close to the second axis relative to the side surface, so as to When the plug connector moves to a spaced position between the limiting protrusion and the bottom surface of the slot opposite to it, the plug connector is limited in the slot; the first part of the slot is The two axes are parallel to each other with the moving direction of the plug in or out of the slot.
  • At least one embodiment of the present disclosure further provides an analysis device, including: a loading part, a transporting part, a temperature control part, and a signal detecting part, wherein,
  • the loading part adopts the above-mentioned chip loading structure provided by at least one embodiment of the present disclosure, is used for carrying the detection chip, and can be detachably connected with the transporting part;
  • the transport portion is configured to transport the chip loading structure
  • the temperature control part includes a heater and a cooler, wherein the heater is configured to heat the detection chip, and the cooler is configured to cool the detection chip;
  • the signal detection section includes an optical sensor, wherein the optical sensor is configured to receive light from the detection chip and perform detection based on the light.
  • the transport unit includes:
  • a transport structure configured to carry the chip loading structure and at least partially drivable
  • a driver configured to drive the transport structure to reciprocate the chip loading structure between a first position, a second position and a third position
  • the first position allows the chip loading structure to be received in the transport structure
  • the second position allows the temperature control section to adjust the temperature of the detection chip
  • the third position allows the optical sensor of the signal detection section to receive the light from the detection chip.
  • the transport structure includes:
  • a movable platform configured to be connected to the drive to move under the drive of the drive
  • a bracket configured to connect the stage and the movable platform, thereby enabling the stage to be brought along when the movable platform is driven.
  • the loading portion adopts the chip loading structure provided in at least one embodiment of the present disclosure
  • a mounting groove for accommodating the loading plate is provided on the bearing surface of the carrier, and a mounting groove opening communicated with the mounting groove is provided on the first side of the carrier for supplying
  • the loading plate body is moved into or out of the installation slot, and the first side surface and the first moving direction of the stage moving into the analysis device are perpendicular to each other, and are backward in the first moving direction side;
  • the stage is also provided with the plug which protrudes from the side surface of the installation groove toward the direction close to the third axis of the installation groove; the third axis and the first The moving directions are parallel to each other.
  • the loading portion adopts the chip loading structure provided in at least one embodiment of the present disclosure
  • the heater comprises at least one contact electrode, at least one of the contact electrodes is configured to be in electrical contact with at least one of the heater electrodes of the detection chip in a one-to-one correspondence in use;
  • the heater is further configured to apply an electrical signal to the heating electrode of the detection chip through the contact electrode, so that the heating electrode heats the detection chip.
  • the contact electrode is fixed on the bearing surface of the stage, and is located on the side of the installation groove opposite to the opening of the installation groove, and one end of the contact electrode is opposite to the installation groove.
  • the sides of the grooves protrude in a direction opposite to the first direction of movement of the stage into the analysis device;
  • the contact electrode is provided with a contact portion for making electrical contact with the heater electrode, the contact portion protruding toward the heater electrode with respect to a surface of the contact electrode opposite to the heater electrode; and , the heater further comprises an elastic member, which is respectively connected with the contact electrode and the stage, so as to apply a pulling force toward the bearing surface of the stage to the contact electrode.
  • the elastic member includes a spring.
  • an electrode slot is provided on the bearing surface of the stage, the contact electrode is inserted in the electrode slot, and the contact electrode and the stage are fixed by fasteners. connect.
  • the signal detection unit further includes:
  • a light source configured to, in use, provide light to illuminate the detection chip
  • a light transmitting section configured to transmit, in use, the light provided by the light source to the detection chip and to transmit light emitted by the detection chip to the optical sensor;
  • the focus adjustment structure is configured to adjust the light transmission part and the detection chip The distance between the detection chips is located at the focal point of the light transmission part; and the focus adjustment structure has a focus adjustment knob and a knob extension part connected with the focus adjustment knob, the knob extension part Extend to the side close to the light transmission part for easy manual adjustment.
  • At least one embodiment of the present disclosure also provides an analysis system, including:
  • the detection chip the detection chip.
  • FIG. 1 is a schematic block diagram of a detection chip according to at least one embodiment of the present disclosure.
  • FIG. 2A is a front structural view of a chip loading structure according to at least one embodiment of the present disclosure.
  • 2B is a rear structural view of a chip loading structure according to at least one embodiment of the present disclosure.
  • 2C is a perspective structural view of a chip loading structure according to at least one embodiment of the present disclosure.
  • FIG. 2D is a perspective structural view of the chip loading structure when the detection chip is carried according to at least one embodiment of the present disclosure.
  • 2E is a front structural view of another chip loading structure according to at least one embodiment of the present disclosure.
  • 2F is a rear structural view of another chip loading structure according to at least one embodiment of the present disclosure.
  • FIG. 3 is a schematic block diagram of an analysis apparatus according to at least one embodiment of the present disclosure.
  • FIG. 4 is a schematic block diagram of a transport section according to at least one embodiment of the present disclosure.
  • 5A is a structural diagram of an exploded state of a transport structure according to at least one embodiment of the present disclosure.
  • 5B is a structural diagram of an assembled state of a transport structure according to at least one embodiment of the present disclosure.
  • 6A is a front structural view of a stage according to at least one embodiment of the present disclosure.
  • 6B is a rear structural view of a stage according to at least one embodiment of the present disclosure.
  • 6C is a perspective structural view of a stage according to at least one embodiment of the present disclosure.
  • 6D is a structural diagram of a contact electrode and a spring member according to at least one embodiment of the present disclosure.
  • FIG. 6E is a structural diagram of a stage when carrying a loading plate body according to at least one embodiment of the present disclosure.
  • FIG. 7A is a schematic structural diagram of a disassembled state of a temperature control portion according to at least one embodiment of the present disclosure.
  • 7B is a structural diagram of an assembled state of a temperature control portion according to at least one embodiment of the present disclosure.
  • FIG. 8 is a schematic block diagram of a signal detection section according to at least one embodiment of the present disclosure.
  • 9A is a side view of a signal detection section according to at least one embodiment of the present disclosure.
  • 9B is another side view of a signal detection portion according to at least one embodiment of the present disclosure.
  • FIG. 10 is an internal structural diagram of an analysis device according to at least one embodiment of the present disclosure.
  • FIG. 11A is an external overall structure diagram of an analysis device according to at least one embodiment of the present disclosure.
  • 11B is an external front view of an analysis device in accordance with at least one embodiment of the present disclosure.
  • 11C is an exterior rear view of an analytical device in accordance with at least one embodiment of the present disclosure.
  • 11D is an external side view of an analysis device in accordance with at least one embodiment of the present disclosure.
  • 11E is another external side view of an analysis device according to at least one embodiment of the present disclosure.
  • 11F is another external side view of an analytical device with a control valve open, according to at least one embodiment of the present disclosure.
  • 11G is an exterior bottom view of an analytical device in accordance with at least one embodiment of the present disclosure.
  • 12A is a state diagram of an analytical device with a loading valve open, according to at least one embodiment of the present disclosure.
  • 12B is a state diagram of the analysis device according to at least one embodiment of the present disclosure when the loading plate body is in the first position.
  • 12C is a state diagram of the analysis device according to at least one embodiment of the present disclosure when the loading plate body is in the second position.
  • 12D is a state diagram of the analysis device according to at least one embodiment of the present disclosure when the loading plate body is in a third position.
  • FIG. 13 is a schematic block diagram of an analysis system in accordance with at least one embodiment of the present disclosure.
  • FIG. 14 is a graph of temperature variation of a temperature control cycle according to at least one embodiment of the present disclosure.
  • FIG. 15 is a schematic outline view of a divided reaction chamber after expansion processing according to an embodiment of the present application.
  • FIG. 16 is a schematic diagram of the amplitude of the Fourier transform of the biochip image to the frequency domain according to the embodiment of the present application.
  • FIG. 17 is a schematic diagram of constructing a filter according to an embodiment of the present application.
  • Some dPCR products usually require multiple sets of ancillary equipment to obtain analytical results, which results in long testing times, high testing costs, multiple operating steps, and the risk of reagent contamination.
  • At least one embodiment of the present disclosure provides a chip loading structure, an analysis device, and an analysis system.
  • the analysis device of this embodiment integrates and integrates a loading part, a temperature control part, and a signal detection part, and realizes the detection of chips with a single device.
  • the detection method reduces the number of required supporting equipment, simplifies the operation steps, shortens the detection time, and reduces the risk of reagent contamination.
  • the detection chip can be protected and the process of putting the detection chip into the transport part can be reduced.
  • the risk of being damaged in the middle can be simplified, and the loading and unloading process of the detection chip installed on the transport part can be simplified, and the installation convenience of the detection chip can be improved.
  • FIG. 1 is a schematic block diagram of a detection chip according to at least one embodiment of the present disclosure.
  • the detection chip 1 has a reaction observation area 12 on one side.
  • the reaction observation area 12 is, for example, a microwell reaction chamber array. area.
  • the detection chip 1 further has a heating electrode 11, and the heating electrode 11 is, for example, in the shape of a rectangular plate.
  • components such as the heating electrode 11 or the resistance traces electrically connected thereto may generate heat to heat the detection chip 1 .
  • the detection chip 1 may also include electrodes for other purposes, such as electrodes for applying electrical signals to drive the sample to move in the detection chip 1 , etc.
  • electrodes for other purposes such as electrodes for applying electrical signals to drive the sample to move in the detection chip 1 , etc.
  • the embodiments of the present disclosure do not make any difference to the type and structure of the detection chip 1 . limit.
  • the detection chip 1 described in the various embodiments of the present disclosure may be any type of biological detection chip or chemical detection chip, such as various microfluidic chips, which are not limited by the embodiments of the present disclosure.
  • 2A is a front structural view of a chip loading structure according to at least one embodiment of the present disclosure.
  • 2B is a rear structural view of a chip loading structure according to at least one embodiment of the present disclosure.
  • 2C is a perspective structural view of a chip loading structure according to at least one embodiment of the present disclosure. Please refer to FIG. 2A to FIG. 2B together.
  • the chip loading structure 2 of the present disclosure it can be detachably connected to the transport part in the analysis device, which can protect the detection chip 1 , This reduces the risk of the detection chip 1 being damaged during the process of being placed in the transport portion, and also simplifies the loading and unloading process of the detection chip 1 installed on the transport portion, thereby improving the installation convenience of the detection chip 1 .
  • the chip loading structure 2 includes a loading plate body 21 , which is, for example, a rectangular plate body, and optionally, is made of a high temperature resistant material to ensure that the detection chip 1 will not be deformed when heated.
  • the loading plate 21 is a rectangular box as a whole, and its outline is generally the same as that of the detection chip 1 .
  • the loading board body 21 has an accommodating space for accommodating the detection chip 1 .
  • the detection chip 1 is located in the accommodating space at this time.
  • the first board surface 2 a of the loading board body 21 is provided with a first hollow area 23 and at least one second hollow area 24 penetrating into the accommodating space.
  • a first hollow area 23 is used to expose the reaction observation area 12 of the detection chip 1 ; each of the second hollow areas 24 is used to expose each reagent port (not shown in the figure) of the detection chip 1 .
  • a first recessed portion 231 may also be provided at the position where the first hollow area 23 is located.
  • the orthographic projection area on the board surface 2a is larger than the orthographic projection area of the first hollow region 23 on the first board surface 2a, and the orthographic projection of the first recessed portion 231 on the first board surface 2a completely covers the first hollow region 23 in the first board surface 2a. Orthographic projection on the first board surface 2a.
  • the arrangement of the first concave portion 231 can expand the observation field.
  • the orthographic projection shape of the first hollow area 23 on the first board surface 2a includes a square, a rectangle or a circle.
  • the orthographic projection shape of the first hollow area 23 on the first board surface 2a shown in FIG. 2A is a square.
  • the embodiment of the present disclosure further provides another chip loading structure 2 ′, in which a first hollow area 23 ′ is provided on the first board surface 2 a ′ of the loading board body 21 ′.
  • the orthographic projection shape of the first hollow area 23' on the first board surface 2a' is a circle. It should be noted that, in practical applications, different types and structures of detection chips 1 may be equipped with corresponding chip loading structures.
  • the direction of , and the first movement direction (ie, the X direction shown in FIG. 2A ) of the transport part moving into the analysis device are parallel to each other.
  • FIG. 2A and FIG. 2B show two second hollow regions 24 , which are spaced apart along the X direction and located on both sides of the first hollow region 23 , respectively.
  • the two second hollow regions 24 may also be located on the same side of the first hollow regions 23 .
  • a second concave portion 241 may be provided at the position of each second hollow area 24 .
  • the orthographic projection area of the two recessed portions 241 on the first board surface 2a is larger than the orthographic projection area of the second hollow region 24 on the first board surface 2a, and the orthographic projection of the second recessed portions 241 on the first board surface 2a is completely The orthographic projection of the second hollow area 24 on the first board surface 2a is covered.
  • the provision of the second concave portion 241 can prevent the reagent from leaking out when filling or discharging the reagent.
  • the rear in the first moving direction ie, the X direction shown in FIG. 2A
  • the orthographic projection area of the second concave portion 241 on the first plate surface 2a is larger than the orthographic projection area of the second concave portion 241 in the front in the first moving direction on the first plate surface 2a.
  • the reagent discharge port is generally located at the front position in the first moving direction (ie, the X direction shown in FIG. 2A ), and when the reagent is filled, the reagent filling port is more likely to leak than the reagent discharge port, so the Appropriately increasing the orthographic projection area of the second concave portion 241 corresponding to the reagent filling port on the first plate surface 2a can further prevent reagent leakage.
  • the orthographic projection of the second concave portion 241 at the rear in the first moving direction on the first board surface 2a is an oval; the second concave portion 241 at the front in the first moving direction is in the first
  • the orthographic projection on a board surface 2a is a circle.
  • the detection chip 1 also has a heating electrode 11.
  • a contact electrode (described in detail below) in the heater, as shown in FIG.
  • the board surface 2 a is provided with a third hollow area 22 penetrating into the above-mentioned accommodating space for exposing the heating electrode 11 .
  • the above-mentioned contact electrode can be in electrical contact with the heating electrode 11 from the side of the first board surface 2a of the loading board body 21 through the third hollow area 22 .
  • the third hollow area 22 extends to the first side of the loading board body 21 , and the first side is connected to the first board.
  • the first axes of the surface 2a are perpendicular to each other; the direction of the first axis when the loading plate body 21 is placed on the above-mentioned conveying part is parallel to the above-mentioned first moving direction (ie, the X direction shown in FIG. 2D ), and The first side is the front side in the first moving direction.
  • the embodiment of the present disclosure also provides another chip loading structure 2 ′, in which the first board surface 2 a ′ of the loading board body 21 ′ is also provided with a second hollow area 24 ′ and a third hollow
  • the area 22 ′ is the same as the arrangement of the second hollow area 24 and the third hollow area 22 , and will not be repeated here.
  • the number and position of the reagent ports of the detection chip 1 may also be different according to different types.
  • the quantity and position of the second hollow regions 24 in the embodiment of the present disclosure can be adaptively designed according to the quantity and position of the reagent ports of the detection chip 1 .
  • hollow regions with other functions may also be provided on the first board surface 2 a of the loading board body 21 , which is not limited in the embodiment of the present disclosure.
  • the above-mentioned accommodating space may have various structures.
  • FIG. 2B on the second board surface 2b of the loading board body 21 that is away from the first board surface 2a
  • An accommodating groove 25 is provided to form the above-mentioned accommodating space. Since the accommodating groove 25 is open on the second board surface 2b, the detection chip 1 can be moved into or out of the container from the side of the second board surface 2b. At the same time, the open accommodating groove 25 helps to improve the cooling efficiency of the detection chip 1, and at the same time, it can also prevent the temperature of the loading board 21 from being too high.
  • a protruding structure is provided on the inner side surface of the accommodating groove 25 to confine the detection chip 1 in the accommodating groove 25 .
  • the above-mentioned protruding structure can have various structures.
  • the protruding structure includes two groups of convex portions distributed on both sides of the above-mentioned first axis (parallel to the X direction) of the first plate surface 2a,
  • Each set of protruding portions includes a plurality of protruding portions 26 spaced along the first axis.
  • the side surfaces of the detection chips 1 in the accommodating grooves 25 abut against each other, so that the detection chips 1 can be fixed in the accommodating grooves 25 under the action of friction.
  • the orthographic projection shape of the convex portion 26 on the second plate surface 2b is designed to be an arc shape such as a semicircle or a semiellipse.
  • the accommodating groove 26 extends to the second side of the second board surface 2b; the second side is perpendicular to the first axis (parallel to the X direction), and the second side The side is the front side in the first moving direction.
  • the heating electrode 11 can correspond to the position of the contact electrode on the transportation part, so as to realize the contact between the two. connect.
  • the embodiment of the present disclosure also provides another chip loading structure 2', which is also provided with an accommodating groove 25' and a convex portion 26' on the second board surface 2b' of the loading board body 21'. , since it is the same as the arrangement of the accommodating groove 25 and the convex portion 26 described above, it will not be repeated here.
  • the loading plate body 21 is further provided with a connecting part 27 , and the connecting part 27 can be detachably connected with the analysis device for transporting the loading
  • the transport portion of the plate body 21 is connected. That is to say, the detection chip 1 is not directly mounted on the transport part, but is mounted on the transport part by means of the loading plate 21, so that it can protect the detection chip 1 and reduce the time when the detection chip 1 is placed in the transport part.
  • the risk of being damaged in the process of transporting the part can also simplify the loading and unloading process of the detection chip 1 installed on the transport part, and improve the installation convenience of the detection chip 1 .
  • the above-mentioned connecting portion 27 can be connected to the above-mentioned transporting portion, for example, by means of plugging.
  • Slot groups are respectively provided on the two side surfaces 2c, and each slot group includes one or a plurality of slots arranged at intervals along the first axis, and the slots are used as the above-mentioned connecting portion 27, for example, as shown in FIG.
  • the slot group provided on each side surface 2c includes two slots (ie, the connecting portion 27 ), and each slot corresponds to the connector in the above-mentioned transport portion (described below) in a one-to-one correspondence
  • the loading plate body 21 can be detachably fixed on the transport part by plugging, and this plugging method is very convenient, simplifies the loading and unloading process of the detection chip 1 installed on the transport part, and improves the installation efficiency.
  • the connecting portion 27 can also be connected with the above-mentioned transporting portion in any other detachable manner, such as snap connection, mechanical fixation, and the like.
  • a socket communicating with the above-mentioned slot is provided on the second board surface 2b of the loading board body 21 that is away from the first board surface 2a.
  • a socket communicating with the above-mentioned slot is provided on the second board surface 2b of the loading board body 21 that is away from the first board surface 2a.
  • the loading plate body 21 When the loading plate body 21 needs to be installed, as shown in FIG. 2C , firstly move the loading plate body 21 downward along the Y direction to move the connector into the slot through the socket along the Y direction, and then translate to the right along the Z direction Load the plate body 21 to move the connector to the left in the Z direction to the upper part of the limiting protrusion 271, that is, move to the spaced position between the limiting protrusion 271 and the bottom surface of the slot opposite to it. At this time, under the action of the cooperating of the limiting protrusion 271 with the plug-in connector, the loading plate 21 cannot move in the Y direction, that is, the loading plate 21 can be fixed on the above-mentioned transporting part.
  • the loading plate body 21 when the loading plate body 21 needs to be unloaded, firstly translate the loading plate body 21 to the left in the Z direction, so as to move the plug connector to the right in the Z direction to a position staggered from the limiting protrusion 271 and opposite to the socket. Then move the loading board body 21 upward along the Y direction to move the plug connector out of the slot through the socket along the Y direction. At this time, the loading board body 21 can move along the Y direction, that is, the loading board body 21 can be moved from the above-mentioned output. Unloading the shipping department.
  • the embodiment of the present disclosure also provides another chip loading structure 2', which is also provided with a connecting portion 27' on the second board surface 2b' of the loading board body 21'.
  • the setting method of the part 27 is the same, and will not be repeated here.
  • FIG. 3 is a schematic block diagram of an analysis apparatus according to at least one embodiment of the present disclosure.
  • the analysis device 100 may include at least a loading part 140 , a transporting part 110 , a temperature controlling part 120 and a signal detecting part 130 .
  • the transportation part 110 adopts the chip loading structure provided in at least one embodiment of the present disclosure, is used for carrying the detection chip 1 , and can be detachably connected with the transportation part 110 .
  • the transport section is configured to transport the chip loading structure
  • the transport section 110 is configured to receive and carry, in use, the loading plate body 21 (carrying the detection chip 1 ) in the chip loading structure described above, and to allow the loading plate body 21 to be moved to the The temperature control part 120 and the signal detection part 130 .
  • the temperature control unit 120 includes a heater 121 and a cooler 122 .
  • the heater 121 is configured to heat the detection chip 1 loaded into the analysis device (carried by the loading plate body 21 ), and the cooler 122 is configured to cool the detection chip 1 loaded into the analysis device, thereby achieving the temperature of the detection chip 1 control.
  • the signal detection unit 130 includes an optical sensor 131 .
  • the optical sensor 131 is configured to receive light from the detection chip 1 and perform detection according to the light of the detection chip 1 .
  • the transport portion 110 may include a transport structure 111 and a driver 112 .
  • the transport structure 111 is configured to carry the above-described chip loading structure (ie, the loading plate 21 ), and can be at least partially driven.
  • the driver 112 is configured to drive the transport structure 111, eg, operatively connected to the transport structure 111, to reciprocate the aforementioned chip loading structure (ie, the loading plate 21) between the first position, the second position and the third position move.
  • the first position allows the aforementioned chip loading structure (ie, loading plate 21 ) to be received in the transport structure 111 , ie, allows the user to place the loading plate 21 into the transport portion 110 , by
  • the loading plate body 21 carries the detection chip 1 loaded with the detection sample.
  • the second position allows the temperature control part 120 to adjust the temperature of the detection chip 1 .
  • the third position allows the optical sensor 131 of the signal detection section 130 to receive light from the detection chip 1 .
  • FIG. 12B an example of the first position in at least one embodiment of the present disclosure is shown in FIG. 12B, which will be described below.
  • An example of the second position in at least one embodiment of the present disclosure is shown, for example, in Figure 12C, which will be described below.
  • An example of a third position in at least one embodiment of the present disclosure is shown, for example, in Figure 12D, which will be described hereinafter.
  • the transport portion 110 may also not include the driver 112, so that the transport structure 111 can be manually moved (eg, pushed or pulled), which is not limited by the embodiments of the present disclosure.
  • FIG. 5A is a structural diagram of an exploded state of a transport structure according to at least one embodiment of the present disclosure
  • FIG. 5B is a structural diagram of an assembled state of the transport structure according to at least one embodiment of the present disclosure.
  • the transport structure 111 may include a stage 1111 , a movable platform 1112 and a bracket 1113 .
  • the stage 1111 is configured to carry the above-mentioned chip loading structure (ie, the loading plate body 21 ) in use, and in the example shown in FIGS. 6A to 6E , the stage 1111 is a rectangular plate, and can be movably mounted on bracket 1113 (as shown in Figure 5B).
  • 6A is a front structural view of a stage according to at least one embodiment of the present disclosure. As shown in FIG. 6A , the stage 1111 can be connected to the connecting portion 27 on the loading plate body 21 in the above-mentioned chip loading structure by plugging.
  • the mounting groove 31 of the loading plate 21 is accommodated, and the first side surface of the stage 1111 is provided with a mounting groove opening 31 a communicating with the mounting groove 31 for the loading plate 21 to move into or out of the mounting groove 31 , as shown in FIG. 6A , the first side surface and the first moving direction (ie, the X direction shown in FIG. 6A ) of the stage 1111 moving into the interior of the analysis device are perpendicular to each other, and are backward in the first moving direction. side.
  • the stage 1111 is also provided with a plug 32 protruding in a direction close to the third axis (parallel to the X direction) of the mounting groove 31 with respect to the side surface of the mounting groove 31 .
  • the protruding portion of the plug connector 32 relative to the side of the mounting slot 31 can be moved into or out of the slot (ie, the connecting portion 27) from the socket along the Y direction.
  • the loading plate 21 placed in the mounting slot 31 can be allowed to translate along the X direction by means of the installation slot opening 31a, so as to enable the plug connector 32 to translate rightward or leftward along the Z direction shown in FIG. 2C . Since the insertion method of the plug connector 32 and the above-mentioned slot has been described in detail above, it will not be repeated here.
  • the stage 1111 may be formed of a high temperature resistant material, and the high temperature resistant material may be, for example, metal, plastic, ceramic, rubber, resin, or the like.
  • the thermal deformation temperature of the high temperature resistant material forming the stage 1111 may be, for example, 100°C, 200°C, 300°C, 400°C, or 500°C or higher.
  • the stage 1111 may also be formed of a material that is resistant to high temperature and has poor thermal conductivity.
  • the stage 1111 may be formed of ceramic, thereby being both lightweight and able to withstand high temperatures.
  • FIG. 6B is a rear structural view of a stage according to at least one embodiment of the present disclosure.
  • the stage 1111 is provided with four through holes 36 penetrating from its back surface 1111b to the bearing surface 1111a, for connecting the stage 1111 and the bracket 1113 with fasteners (such as screws or bolts) Fixed connection.
  • fasteners such as screws or bolts
  • four compression springs can be used to connect the stage 1111 and the bracket 1113 to exert an elastic force toward the two to keep them away from each other.
  • the fasteners can be tightened or loosened, To adjust the distance between the stage 1111 and the bracket 1113, the levelness of the stage 1111 can be adjusted.
  • the above-mentioned four compression springs may be sleeved on the above-mentioned fasteners.
  • the levelness of the stage 1111 can also be adjusted by setting other leveling structures, which is not limited by the embodiments of the present disclosure.
  • the stage 1111 may further include a spirit level to detect whether the stage 1111 is level.
  • the spirit level may be adhered to the stage 1111 through an adhesive or the like, which is not limited by the embodiment of the present disclosure.
  • the level may be, for example, a bubble level, an inductive level, a capacitive level, etc., which are not limited in the embodiments of the present disclosure.
  • the stage 1111 may have a hollow area 34 so that when the loading board 21 is placed on the stage 1111 , the contact surface of the loading board 21 and the stage 1111 is at least partially exposed, for example Exposed to the cooler 122 of the temperature control part 120 .
  • the detection chip 1 carried by the loading board 21 can be exposed to the temperature control part 120 .
  • the cooler 122 can improve the cooling efficiency of the detection chip 1 .
  • the hollow area 34 can have any suitable shape, such as a circle, a triangle, a rectangle, a pentagon, a hexagon or other irregular shapes; for example, the hollow area 34 can have one or more openings, The embodiments of the present disclosure do not limit this.
  • the size of the projection of the loading plate 21 on the plane where the hollow area 34 is located is larger than the size of the hollow area 34 , so that the loading plate 21 will not be separated from the stage 1111 from the hollow area 34 .
  • the heater 121 may include at least one contact electrode 33 , and the contact electrode 33 may be formed of, for example, a high temperature resistant metal material.
  • the at least one contact electrode 33 is configured to be in electrical contact with the at least one heater electrode 11 of the detection chip 1 in a one-to-one correspondence in use.
  • the heater 121 is also configured to apply an electrical signal to the heating electrode 11 of the detection chip 1 through the contact electrode 33 , so that the heating electrode 11 heats the detection chip 1 .
  • the contact electrode 33 is fixed on the bearing surface 1111a of the stage 1111 on the side opposite to the mounting slot opening 31a, and one end of the contact electrode 33 is opposite to the mounting groove opening 31a.
  • the side surface of the mounting groove 31 protrudes in the opposite direction to the X direction, that is, the contact electrode 33 extends from one side of the mounting groove 31 to the inside of the mounting groove 31 to allow contact with the exposed heating electrode 11 of the detection chip 1 in use
  • Electrical contact is made to apply an electrical signal (eg, a DC voltage or an AC voltage) to the heating electrode 11 of the detection chip 1 .
  • an electrical signal eg, a DC voltage or an AC voltage
  • the contact electrode 33 When the detection chip 1 is placed on the stage 1111, the contact electrode 33 is in electrical contact with the heating electrode 11 of the detection chip 1, so that electrical signals can be transmitted.
  • the contact electrodes 33 may be electrically connected to a power source or a controller through wiring through the stage 1111 to receive control signals.
  • the contact electrode 33 is provided with a contact portion 331 for electrical contact with the heating electrode 11 , and the contact portion 331 protrudes toward the heating electrode 11 relative to the surface of the contact electrode 33 opposite to the heating electrode 11 .
  • the contact portion 331 is a convex portion formed by bending one end of the contact electrode 33 , and the convex portion preferably forms an acute angle with the contact electrode 33 to facilitate the insertion of the heating electrode 11 of the detection chip 1 to the inner side of the contact electrode 33 .
  • the heater 121 further includes an elastic member 35 , which is connected to the contact electrode 33 and the stage 1111 respectively, and is used to apply a force to the contact electrode 33 toward the bearing surface 1111 a of the stage 1111 . pull.
  • the elastic member 35 By means of the elastic member 35 , the elastic connection between the contact electrode 33 and the stage 1111 can be realized, and the contact electrode 33 can be reset when the loading plate 21 is moved out of the mounting groove 31 .
  • the above-mentioned elastic member 35 is a spring, such as a tension spring.
  • a limiting groove 333 may be provided on the contact electrode 33 to limit the position of the elastic member 35 on the contact electrode 33 .
  • an electrode slot 312 is provided on the bearing surface 1111 a of the stage 1111 , the contact electrode 33 is inserted in the electrode slot 312 , and the contact electrode 33 is connected to the stage. 1111 is fixedly connected by fasteners.
  • a mounting hole 332 can be provided at one end of the contact electrode 33 away from the contact portion 331, and fixed to the stage 1111 by fasteners (such as screws or bolts). connect.
  • limit steps 311 are further provided at the two corners of the side surface of the installation groove 31 opposite to the installation groove opening 31 a to limit the position of the loading plate 21 in the installation groove 31 .
  • a certain contact space can be reserved for the heating electrode 11 and the contact electrode 33 of the detection chip 1 carried by it.
  • the detection chip 1 may not have heating electrodes, and the heater 121 may be configured to provide heating infrared rays or airflow to the detection chip 1 to heat the detection chip 1 .
  • the heater 121 may be an infrared heater or a gas heater (for example, heating the air through resistance and driving the heated air to flow through a fan), etc., which is not limited by the embodiment of the present disclosure.
  • the movable platform 1112 is configured to be operably connected to the drive 112 for movement under the drive of the drive 112 .
  • the driver 112 can be, for example, a motor, and the movable platform 1112 is, for example, connected to a driving end of the motor.
  • the driver 112 may be a rotary motor, and the driving end of the rotary motor is connected with the lead screw S, so that the lead screw S can be rotated, and the movable platform 1112 is threaded through a nut engaged with the lead screw S.
  • the driver 112 can be a linear motor, and the mover of the linear motor can be connected with the movable platform 1112 to drive the movable platform 1112 to move.
  • the embodiment of the present disclosure does not limit how the driver 112 drives the movable platform 1112, for example, a rack and pinion combination can also be used to convert rotational motion into horizontal motion.
  • the movable platform 1112 may be formed of any rigid material, eg, metal, plastic, ceramic, rubber, resin, etc., which are not limited by embodiments of the present disclosure.
  • the shapes of the movable platform 1112 shown in FIGS. 5A and 5B are only exemplary, and the movable platform 1112 may have any suitable shape according to actual requirements.
  • the bracket 1113 is configured to connect the stage 1111 and the movable platform 1112, thereby enabling the stage 1111 to be brought along when the movable platform 1112 is driven.
  • the bracket 1113 may include a first portion 1113A and a second portion 1113B, as shown by the dashed box in FIG. 5A .
  • the first portion 1113A is configured to carry the stage 1111 in use.
  • the second portion 1113B is configured to be connected to the movable platform 1112 in use.
  • the first portion 1113A extends in a first direction
  • the second portion 1113B extends in a second direction
  • the first direction is perpendicular to the second direction. Forming the holder 1113 into an L-shape or a T-shape, thereby reducing the size in a single direction, helps to reduce the overall volume of the analysis device.
  • the first part 1113A of the bracket 1113 can be connected to the stage 1111 through springs, for example, for example, through four springs corresponding to the four corners of the stage 1111, so that the horizontal state of the stage 1111 can be adjusted by adjusting the corresponding springs .
  • the second part 1113B of the bracket 1113 can be detachably connected or fixedly connected with the movable platform 1112 by, for example, screws or the like, so as to allow the movable platform 1112 to drive the bracket 1113 to move together.
  • the second portion 1113B may be integrally formed with the movable platform 1112 .
  • the bracket 1113 may be formed of any rigid material, for example, metal, plastic, ceramic, rubber, resin, etc., which is not limited by the embodiments of the present disclosure.
  • the shape of the bracket 1113 shown in FIGS. 5A and 5B is only exemplary, and the bracket 1113 may have any suitable shape according to actual requirements.
  • the temperature control part 120 may include, for example, a temperature sensor 123 .
  • the temperature sensor 123 is configured to detect the temperature of the detection chip 1 .
  • the temperature sensor 123 may use a conventional temperature sensor, which will not be repeated in this embodiment of the present disclosure.
  • the temperature sensor 123 may include an infrared temperature sensor or a thermocouple temperature sensor. It should be understood that, in some embodiments of the present disclosure, if the detection chip 1 includes a temperature sensor, the temperature sensor 123 does not need to be disposed in the analysis device.
  • the temperature sensor 123 and the cooler 122 are configured to be spaced apart from each other to allow the detection chip 1 to be sandwiched between the temperature sensor 123 and the cooler 122 .
  • the temperature control part 120 may further include a temperature control bracket 124 to which the temperature sensor 123 and the cooler 122 are connected to be spaced apart from each other. It should be understood that the positions of the temperature sensor 123 and the cooler 122 in FIGS. 7A and 7B are only exemplary, and the embodiments of the present disclosure are not limited thereto.
  • the temperature sensor 123 may be above or below the detection chip 1 in use, and the cooler 122 may be on the side of the detection chip 1 in use.
  • the cooler 122 may include, but is not limited to, a fan or a semiconductor refrigeration chip, and the embodiment of the present disclosure does not limit the specific type of the cooler 122 .
  • the cooler 122 can be exemplified as a fan, which has a substantially circular shape and is fixed in the temperature control bracket 124 by four mounting posts 122 a provided at four corners.
  • the base of the temperature control bracket 124 is provided with four through holes 124 a for installing the four mounting posts 122 a on the base of the temperature control bracket 124 through screws in a one-to-one correspondence.
  • the temperature control bracket 124 is composed of a bottom plate and a vertical plate and a horizontal plate arranged on the bottom plate.
  • the horizontal plate is relatively arranged above the bottom plate and supported by the vertical plate.
  • the cooler 122 Supported by the bottom plate, the temperature sensor 123 is arranged on the horizontal plate and is relatively positioned above the cooler 122 .
  • the temperature sensor 123 can detect the temperature of the detection chip 1; the cooler 122 can cool the detection chip 1.
  • a rib 124b is further provided at the included angle between the horizontal plate and the vertical plate, so as to strengthen the connection stability of the horizontal plate and the vertical plate.
  • the rib 124b is perpendicular to the above-mentioned horizontal and vertical plates, and the two sides are at right angles, so as to fit with the above-mentioned horizontal and vertical plates respectively, and the rib 124b also has wavy sides for the cooler 122. Provide installation space.
  • the temperature control bracket 124 may be formed of any rigid material, for example, metal, plastic, ceramic, rubber, resin, etc., which is not limited by the embodiments of the present disclosure.
  • the shape of the temperature control bracket 124 shown in FIGS. 7A and 7B is only exemplary, and the temperature control bracket 124 may have any suitable shape according to actual requirements.
  • FIG. 8 is a schematic block diagram of a signal detection section according to at least one embodiment of the present disclosure.
  • the signal detection part 130 may further include a light source 132 and a light transmission part 133 .
  • the optical sensor 131 is, for example, an image sensor configured to acquire images of the detection chip (eg, biochip images) for analysis.
  • the optical sensor 131 may include a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS).
  • CCD charge coupled device
  • CMOS complementary metal oxide semiconductor
  • the optical sensor 131 may also be a photodiode, a photoresistor, an infrared sensor, an ultraviolet sensor, etc., which are not limited in the embodiments of the present disclosure.
  • the light source 132 may be configured to provide light, in use, to illuminate the detection chip.
  • the light transmission part 133 may be configured to transmit light provided by the light source 132 to the detection chip and light emitted by the detection chip to the optical sensor 131 in use.
  • the light source 132 can be of various types and can emit visible light, infrared light, etc., for example, including a laser or a fluorescent light source.
  • the wavelengths of the laser and the fluorescent light source can be selected according to actual needs, which are not limited by the embodiments of the present disclosure.
  • the light transmission part 133 may include a 90° turning prism system 1331 and a reflective light path system 1332 .
  • the 90° turning prism system 1331 may be configured to transfer light from the detection chip. The light is transmitted to the optical sensor 131 .
  • the reflective light path system 1332 may be configured to transmit light from the light source 132 to illuminate the detection chip, and the reflective light path system 1332 may further include a filter on the light path from the detection chip to the optical sensor 131 to illuminate the detection chip. The light transmitted on the optical path is filtered, and only the light of the set wavelength is allowed to pass through.
  • Both the 90° turning prism system 1331 and the reflection light path system 1332 can adopt conventional designs in the art, which will not be repeated in this disclosure.
  • the signal detection part 130 may further include an objective lens 134 .
  • the objective lens 134 is configured to collect light from the detection chip.
  • objective lens 134 may include a lens.
  • the signal detection part 130 may further include a bracket 135 .
  • the bracket 135 is used to fix and carry at least some components in the information detection part 130 , such as the light source 132 , the light transmission part 133 and the like.
  • the bracket 135 is further provided with a focal length adjusting structure, the focal length adjusting structure is configured to adjust the distance between the light transmission part 133 and the detection chip, so that the detection chip is at the focus of the light transmission part 133 .
  • the focus adjustment structure has a focus adjustment knob 136 and a knob extension portion 1361 connected to the focus adjustment knob 136 , and the knob extension portion 1361 extends to a side close to the light transmission portion 133 to facilitate manual adjustment .
  • the bracket 135 may adopt a conventional design in the art, which will not be repeated in this disclosure.
  • the signal detection part 130 may further include a level meter (not shown in the figure) to detect whether the signal detection part 130 is level.
  • a spirit level may be connected to the light transmission part 133, the optical sensor 131, the light source 132, and the like.
  • a spirit level may be connected to the 90° turning prism system 1331 .
  • the spirit level is connected to other components of the signal detection part 130 in any suitable manner, such as bonding, magnetic adsorption, screw connection, etc., which is not limited by the embodiment of the present disclosure.
  • the level may be, for example, a bubble level, an inductive level, a capacitive level, etc., which are not limited in the embodiments of the present disclosure.
  • the level can make the light transmitted from the light transmission part 133 to the detection chip perpendicular to the detection chip or the light from the detection chip to enter the light transmission part 133 vertically, so as to facilitate subsequent signal processing, for example, the image processing of the detection chip can be omitted. Steps for angle correction.
  • FIG. 10 is an internal structural diagram of an analysis device according to at least one embodiment of the present disclosure.
  • the analysis device may include a base 101 , and the transport part 110 , the temperature control part 120 and the signal detection part 130 are all arranged on the base 101 , for example, fixed on the base 101 by screws, clamps, adhesives, etc. .
  • the temperature control part 120 and the signal detection part 130 can be arranged along the moving path of the movable platform 1112 in the transport part 110 , so that the movement of the movable platform 1112 can drive the loading plate 21 carried on the object platform 1111 to move To the temperature control part 120 for temperature control and move to the signal detection part 130 to collect the light from the detection chip.
  • FIG. 10 is exemplary, and different arrangements may be adopted according to the different structures and shapes of the transport part 110 , the temperature control part 120 and the signal detection part 130 .
  • the example does not limit this.
  • the analytical device 100 further includes one or more controllers.
  • the one or more controllers can be configured to perform at least one of the following operations:
  • the above-mentioned controller can be implemented by, for example, a central processing unit (CPU), a digital signal processor (DSP), a single-chip microcomputer, a field programmable gate array (FPGA), a complex programmable logic device (CPLD), an application specific integrated circuit (ASIC), etc.,
  • CPU central processing unit
  • DSP digital signal processor
  • FPGA field programmable gate array
  • CPLD complex programmable logic device
  • ASIC application specific integrated circuit
  • the controller may be implemented as a plurality of sub-controllers, and the plurality of sub-controllers may respectively perform at least one of the above operations.
  • the plurality of sub-controllers can be separately provided or integrated in one controller, which is not limited by the embodiments of the present disclosure.
  • the analysis device 100 may further include a communication section.
  • the communication section is configured to form a signal connection with a mobile terminal, a server, and the like.
  • the signal connection may be a wired connection or a wireless connection, which is not limited by the embodiments of the present disclosure.
  • Exemplary wireless connections include Wireless Fidelity (Wi-Fi), Bluetooth, Wireless Direct, and Infrared.
  • Exemplary wired connections include Universal Serial Bus (USB), FireWire, Thunderbolt, or any connection that requires a physical cable.
  • the analyzing apparatus may further include a display screen 201 .
  • the display screen 201 is, for example, disposed on the front of the housing 200 and configured to display, for example, a liquid crystal display screen, an organic light emitting diode (OLED) display screen, a quantum dot light emitting diode (QLED) display screen, a micro light emitting diode display screen, An electronic ink screen, an electronic paper display screen, etc., are not limited in the embodiments of the present disclosure.
  • the display screen 201 may be a touch screen display to receive user input.
  • the analysis device may not include the display screen 201, but may be connected to a separately set display screen or output data such as analysis results in the form of digital files or physical files. This is not limited.
  • the front surface of the housing 200 may further be provided with a loading valve 202 , which, when opened, allows the stage 1111 to protrude therefrom to receive the loading plate 21 .
  • the analysis device may further include a power interface 203 .
  • the power interface 203 is, for example, disposed on the back of the housing 200 , and the analysis device is connected to the power source through the power interface 203 to obtain electric power.
  • the analysis device may not have the power interface 203, but has a built-in primary battery or a secondary battery, or a built-in solar battery, which is not limited by the embodiments of the present disclosure.
  • the analysis apparatus may further include a data transmission interface 204 .
  • the data transmission interface 204 is provided on the back of the housing 200, for example, and is configured to output data of the analysis device, such as analysis results, to an external device, or to transmit data from an external device to the analysis device.
  • the data transmission interface 204 may be, for example, a Universal Serial Bus (USB) interface, a Serial Advanced Technology Attachment (SATA) interface, or the like.
  • USB Universal Serial Bus
  • SATA Serial Advanced Technology Attachment
  • the data transmission interface and the power interface can be combined into one interface, such as a USB interface, which can be used for both data transmission and power transmission.
  • the analysis device according to at least one embodiment of the present disclosure may further include a key.
  • the key is configured to obtain an input instruction from the user, and may be, for example, a mechanical key, an optical key, or the like, which is not limited in the embodiments of the present disclosure.
  • the analysis device may further include a power switch 207 and an indicator light 208 , both of which are disposed on one side of the housing 200 , for example.
  • the analytical device may further include a control valve 209 , eg, disposed on one side of the housing 200 (which may be on a different side from the power switch 207 and indicator light 208 described above).
  • a control valve 209 eg, disposed on one side of the housing 200 (which may be on a different side from the power switch 207 and indicator light 208 described above).
  • FIG. 11F after the control valve 209 is removed, a magnetic patch 211 is disposed on the inner side thereof to fix the control valve 209 by magnetic adsorption.
  • the control valve 209 can also be detachably fixed on the casing 200 in other ways, or the control valve 209 can be movably connected to the casing 200 to open or close the control opening.
  • the filter wheel 212 is exposed from the control opening to enable manual selection of the fluorescence channel.
  • the knob extension 1361 can also be exposed for manual focus adjustment.
  • the focal length adjustment can also have two working modes: one is to use the knob extension part 1361 for manual adjustment, and the other is to use the built-in automatic control part to automatically adjust the focal length.
  • the analysis device may further include four supporting feet 213 , and the four supporting feet 213 are disposed on the bottom surface of the housing 200 .
  • the four supporting feet 213 have level adjustment structures (for example, including screws and elastic members), so as to be able to adjust the level of the whole analysis device.
  • the analysis device may further include a heat dissipation port 205 , a heat dissipation port 206 and a heat dissipation port 210 , which are respectively disposed on the back and both sides of the housing 200 , It can be used to release the heat of the controller or the temperature control part 120 .
  • These vents can be packaged in a dust-free package to prevent dust from entering the interior of the analytical unit.
  • the analysis device may further include a touch sensor.
  • the touch sensor is configured to receive and detect a user's touch operation, and convert the user's touch operation into an electrical signal to transmit to a controller or other control devices, such as a controller or an external server.
  • the touch sensor may be, for example, a capacitive touch sensor, a resistive touch sensor, etc., which are not limited in the embodiments of the present disclosure. It should be understood that when the display screen 201 is a touch display screen or the analysis device includes other forms of input devices (eg, keys, microphones, etc.), the analysis device may also not include a touch sensor.
  • FIG. 12A to 12D illustrate state diagrams of the analysis device according to at least one embodiment of the present disclosure when the loading plate body 21 is located at different positions.
  • the loading valve 202 of the analysis device is opened, and the stage 1111 protrudes from the chip loading port of the analysis device to receive the loading plate 21 .
  • the loading board 21 (carrying the detection chip) is at the first position where the loading board 21 is received and carried on the stage 1111 .
  • FIG. 12A illustrates state diagrams of the analysis device according to at least one embodiment of the present disclosure when the loading plate body 21 is located at different positions.
  • the loading valve 202 of the analysis device is opened, and the stage 1111 protrudes from the chip loading port of the analysis device to receive the loading plate 21 .
  • the loading board 21 (carrying the detection chip) is at the first position where the loading board 21 is received and carried on the stage 1111 .
  • the loading board 21 is in the second position, and the loading board 21 is located between the temperature sensor 123 on the temperature measuring bracket 124 and the cooler 122, and the temperature sensor 123 can detect the temperature of the detection chip; cooling The device 122 can cool the detection chip.
  • the second position allows the temperature control unit 130 to adjust the temperature of the detection chip.
  • the loading plate 21 is at the third position, and the loading plate 21 is located below the objective lens 134 at this time, so that the objective lens 134 can collect the light from the detection chip.
  • At least one embodiment of the present disclosure also provides an analysis system.
  • 13 is a schematic block diagram of an analysis system in accordance with at least one embodiment of the present disclosure.
  • the analysis system 300 includes an analysis device 310 and a detection chip 320 .
  • a combination of the analysis device 310 and an unused detection chip 320 can be provided to a user for use by the user.
  • the analysis device 310 may be any of the analysis devices described above.
  • the detection chip 320 may be any of the above-mentioned detection chips.
  • the analysis system 300 may further include more components or components, which are not limited by the embodiments of the present disclosure.
  • the analysis device 310 and the detection chip 320 reference may be made to the description of the reaction device above, which will not be repeated here.
  • At least one embodiment of the present disclosure also provides a method of operating an analytical device.
  • the method is applicable to the analysis device according to any embodiment of the present disclosure.
  • a method of operating an analysis device according to at least one embodiment of the present disclosure may include the steps of:
  • Step 1 move the transporting part carrying the loading part (ie, the loading plate body carrying the detection chip in the chip loading structure) to the temperature control part.
  • step 1 the above-mentioned transport part can be manually moved to the temperature control part.
  • the transport includes a transport structure configured to carry the loading plate and at least partially drivable and a drive configured to drive the transport structure
  • step 1 may comprise driving the transport carrying the loading plate by the drive This structure is used to move the loading plate body to the temperature control part.
  • FIG. 12A to 12D illustrate state diagrams of the analysis device according to at least one embodiment of the present disclosure when the loading plate body 21 is located at different positions.
  • the loading valve 202 of the analysis device is opened, and the stage 1111 protrudes from the chip loading port of the analysis device to receive the loading plate 21 .
  • the loading board 21 (carrying the detection chip) is at the first position where the loading board 21 is received and carried on the stage 1111 .
  • FIG. 12A illustrates state diagrams of the analysis device according to at least one embodiment of the present disclosure when the loading plate body 21 is located at different positions.
  • the loading valve 202 of the analysis device is opened, and the stage 1111 protrudes from the chip loading port of the analysis device to receive the loading plate 21 .
  • the loading board 21 (carrying the detection chip) is at the first position where the loading board 21 is received and carried on the stage 1111 .
  • the loading board 21 is in the second position, and the loading board 21 is located between the temperature sensor 123 on the temperature measuring bracket 124 and the cooler 122, and the temperature sensor 123 can detect the temperature of the detection chip; cooling The device 122 can cool the detection chip.
  • the second position allows the temperature control unit 130 to adjust the temperature of the detection chip.
  • Step 2 adjust the temperature of the detection chip through a heater and a cooler.
  • step 2 may include applying an electrical signal to the heating electrode of the detection chip through the contact electrode, so that the heating electrode heats the detection chip.
  • step 2 further includes: cyclically maintaining the detection chip at at least two temperatures through a heater and a cooler.
  • the detection chip is heated by a heater and cooled by a cooler, and multiple temperature control cycles, such as 30 temperature control cycles, are performed on the detection chip, so that the detection chip performs PCR thermal cycle amplification.
  • Each temperature control cycle includes: maintaining the detection chip at 95° C. for 10 seconds; maintaining the detection chip at 50° C. for 10 seconds; maintaining the detection chip at 72° C. for 10 seconds.
  • 14 is a graph of temperature variation of a temperature control cycle according to at least one embodiment of the present disclosure. In Fig. 14, the horizontal axis represents time in minutes, and the vertical axis represents temperature in degrees Celsius.
  • Step 3 Move the transport part to the signal detection part, and obtain the light from the detection chip through the optical sensor.
  • step 3 the above-mentioned transporting part can be manually moved to the signal detecting part.
  • the transport portion described above comprises a transport structure configured to carry the loading plate and at least partially drivable and a driver configured to drive the transport structure
  • step 3 may include driving the transport portion by the driver to drive the transport structure
  • the detection chip moves to the signal detection unit.
  • the loading plate 21 is at the third position, and the loading plate 21 is located below the objective lens 134 at this time, so that the objective lens 134 can collect the light from the detection chip.
  • Step 3 may further include: irradiating the detection chip with light, and receiving the light emitted by the detection chip as the light from the detection chip through the optical sensor.
  • step 3 may include obtaining an image of the detection chip through the image sensor.
  • step 3 may include: providing light through the light source; transmitting the light provided by the light source through the light transmission part to illuminate the detection chip; and sending out the detection chip through the light transmission part The light is transmitted to the optical sensor (or the image sensor included in the optical sensor) as light from the detection chip.
  • Step 4 analyze the light from the detection chip to obtain an analysis result.
  • one or more steps and at least part of the sub-steps in the above-mentioned method may be executed by software or firmware, for example, by a mobile terminal, a server, etc. that are signally connected to the analysis device, which is not limited by the embodiments of the present disclosure. .
  • step 4 may adopt the following method of the image of the biochip The analysis method recognizes the matrix biochip fluorescence image of high-throughput and low signal-to-noise ratio, and realizes the automatic analysis of chamber location positioning and sample negative and positive judgment.
  • the analysis method of the biochip image includes:
  • Step 41 obtaining a biochip image and preprocessing to obtain a preprocessed image
  • Step 42 performing angular deflection correction on the preprocessed image to obtain a deflection corrected image
  • Step 43 performing enhancement processing on the deflection corrected image, and identifying the negative and positive of the region of interest in the preprocessed image according to the enhanced image.
  • the above step 41 includes:
  • Step 411 obtain the original image, the camera intrinsic parameter matrix and the distortion coefficient
  • Step 412 Correct the original image according to the camera internal parameter matrix and the distortion coefficient to obtain a biochip image.
  • the distortion generated in the original image collected by the camera can be corrected by acquiring the camera internal parameter matrix and the distortion coefficient, so that the corrected biochip image can more truly display the characteristics of the biochip. In this way, it can be beneficial to ensure the validity and accuracy of the biochip analysis.
  • the biochip may be quadrilateral, and a plurality of reaction chambers are arranged in an array on the biochip. It should be noted that, in the embodiments of the present application, the region where the reaction chamber is located in the biochip image is used as the region of interest for description.
  • the method for analyzing the biochip image includes: using a calibration plate to calibrate the camera used for shooting by using a traditional calibration method, so as to obtain the camera's internal parameter matrix and distortion coefficient.
  • the calibration plate when the camera parameters are calibrated by the calibration plate, the calibration plate may have a predetermined pattern, such as a grid pattern or a black and white square pattern, etc., and the camera captures an image of the calibration plate at a certain shooting distance. The image is compared with the pattern of the calibration plate. According to the offset of the corresponding feature points in the image of the calibration plate and the pattern of the calibration plate, combined with the shooting distance, the camera internal parameter matrix and distortion parameters related to the camera shooting are obtained.
  • a predetermined pattern such as a grid pattern or a black and white square pattern, etc.
  • the camera internal parameter matrix and distortion coefficient may be pre-calibrated and pre-stored in the analysis device of the camera or biochip image.
  • the analysis device may obtain the corresponding camera internal parameter matrix and distortion from the camera. coefficient, or determine the camera's intrinsic parameter matrix and distortion coefficient according to the camera's serial number or model.
  • the analysis device may also detect the camera internal parameter matrix and distortion coefficient corresponding to the corresponding camera before each acquisition of an image of the biochip. In this way, the validity of the camera internal parameter matrix and distortion coefficient can be ensured.
  • the original image is a fluorescent image of the biochip in which the biochemical reaction has occurred.
  • the fluorescence image of the corresponding biochip can be collected by using a specific device. It can be understood that, in the fluorescence image, the color and brightness displayed by different reaction chambers may be the same or different.
  • the preprocessed image includes a high-frequency component image
  • the above step 41 includes:
  • Step 413 performing Gaussian filtering on the biochip image to obtain a low-frequency component image
  • Step 414 subtract the low-frequency component image from the biochip image to obtain the high-frequency component image.
  • Gaussian filtering is used to obtain a low-frequency component image, and then the low-frequency component in the biochip image is subtracted to obtain a high-frequency component image, so as to achieve high-frequency filtering and solve the problem of uneven fluorescence illumination of the microchip.
  • the preprocessed images may not be limited to the high-frequency component images discussed above, and grayscale images, low-frequency component images, edge detection images, etc. may be obtained according to actual requirements.
  • the grayscale image can be obtained according to the grayscale processing of the image
  • the low-frequency component image can be obtained by the low-frequency component extraction process
  • the edge detection image can be obtained by the image edge extraction process.
  • the preprocessed image can also be obtained by processing one or more of the above processing methods in a preset order, which is not specifically limited here.
  • the above step 42 includes:
  • Step 421 selecting a preset number of detection areas in the preprocessed image
  • Step 422 using the Hough circle transform to detect the center and radius of the region of interest within the detection region.
  • Step 423 making a circle according to the center and radius of the region of interest to determine the region of interest and segment the region of interest.
  • the region of interest as the region where the reaction chambers are located in the image as an example, when detecting the arrangement of the reaction chambers, it is necessary to determine the positions of the reaction chambers in the detection area. Since the reaction chambers are generally circular, so, through Hough The transformation can realize the detection of the center and radius of the chamber, and further, after the position of the reaction chamber is determined according to the center and radius of the chamber, the segmentation of the reaction chamber can be realized.
  • the above step 421 includes: selecting a corresponding detection area within a predetermined area of the preprocessed image.
  • the preset area may be set by the user according to experience, or automatically selected according to an algorithm.
  • the detection area can also be an area randomly selected in the preprocessed image, which is not specifically limited here.
  • the detection area is a rectangular area, and the detection area includes part of the region of interest in at least two rows or at least two columns.
  • the deflection angle of the high frequency component image needs to be determined. Because the reaction chambers on the biochip are generally arranged in an array, that is, the regions of interest are generally arranged in an array, so the detection of the image deflection angle can be realized by the arrangement direction of the chambers, and the use of a rectangular area is conducive to determining the long side direction of the selected detection area. The relative deflection angle to the alignment direction of the reaction chambers.
  • the detection area includes at least two rows or at least two columns of part of the region of interest, which can ensure the detection of the arrangement direction of the reaction chambers.
  • the size of the detection area can be flexibly configured according to the area spacing of the area of interest and the radius of the area of interest, etc., which is not specifically limited here.
  • the shape of the detection area may not be limited to the rectangle discussed above, and other suitable shapes such as square, triangle, circle, parallelogram, etc. may be selected according to actual needs, which are not specifically limited here.
  • the preset number of detection areas selected each time may be multiple, and the directions of the multiple detection areas may be different, thereby improving the efficiency and accuracy of image deflection angle detection.
  • the preset number of detection regions selected each time may be nine.
  • the above step 42 includes:
  • Step 424 performing dilation processing on the segmented image to connect adjacent regions of interest in a preset direction
  • Step 425 taking the largest contour in the detection area after the expansion process and performing principal component analysis to obtain the contour direction
  • Step 426 Determine the deflection angle of the image according to the contour direction to correct the preprocessed image to obtain a deflection corrected image.
  • the segmented region of interest may be expanded in a preset direction, so that the contour of the region of interest extends along the preset direction, so that the contours of adjacent regions of interest are connected to each other.
  • the preset direction may be the long side direction of the rectangular detection area.
  • Fig. 15 shows a schematic diagram of the outline obtained by expanding the regions of interest in the nine chambers in a preset direction when there are nine detection regions.
  • the largest contour in the detection region is selected for PCA principal component analysis to obtain the contour direction.
  • the obtained contour direction can be used as the arrangement direction of the reaction chambers. In particular, when there are multiple detection areas, you can perform PCA principal component analysis on the largest contour in the multiple detection areas to obtain the contour direction.
  • step 425 can determine the image deflection angle of the biochip image and the preprocessing image according to the contour direction, and perform deflection angle correction on the biochip image and/or the preprocessing quantity image to obtain a deflection corrected image.
  • the present application can solve the problem of deflection angle detection by adjoining the same-direction region of interest to form the largest contour and then using the PCA principal component analysis method.
  • the above step 42 includes:
  • Step 427 re-selecting a preset number of detection areas randomly in the preprocessed image by increasing the selection area with a preset ratio
  • Step 428 iteratively detect the deflection angle of the image until the deflection angle of the image is smaller than a preset angle threshold to obtain a deflection corrected image.
  • the image deflection angle is repeatedly and iteratively detected through detection regions of different sizes, thereby ensuring the accuracy of the image deflection angle.
  • the preset angle threshold value range can be determined by the following conditional formula:
  • is the preset angle threshold
  • dist is the area distance of the area of interest
  • rad is the area radius of the area of interest
  • m is the number of rows of the area of interest in the detection area
  • n is the number of columns of the area of interest in the detection area.
  • the biochip image can be accurately aligned with the help of hardware equipment during shooting, so that the deflection correction image can be directly determined according to the biochip image shot after accurate alignment. In this case, it can be omitted.
  • a marker bit may also be set on the biochip entity. After the biochip image is acquired, a relative coordinate system can be constructed by identifying the marker bit on the biochip, and the deflection angle of the chip relative to the camera can be obtained, and then the deflection correction can be obtained by correction. image.
  • angle deflection correction may not be limited to the embodiments discussed above, and an appropriate correction method may be selected according to the actual situation, so that the analysis device can determine that the region of interest on the chip satisfies the horizontal or vertical arrangement relative position according to the deflection correction image. Make specific restrictions.
  • the above step 42 includes:
  • Step 427' increase the selection area with a preset ratio and randomly select a preset number of detection areas in the preprocessed image.
  • Step 428' repeating iteratively detecting the deflection angle of the image for a preset number of times to obtain a deflection corrected image.
  • the preset number of times may be preset by the system or set by a user according to actual conditions, for example, the preset number of times may be 6 times.
  • the above step 43 includes:
  • Step 431 build a notch filter
  • Step 432 filtering the deflection corrected image by using a notch filter to obtain a periodic pattern enhanced image.
  • a notch filter can make the time and space complexity of the algorithm of the biochip image analysis method of the embodiment of the present application lower, and the performance requirements of the hardware device are more relaxed, thereby reducing the cost and improving the operation while ensuring the effect. efficiency.
  • the above step 433 includes:
  • Step 4331 using a box filter to perform smooth filtering processing on the periodic pattern enhanced image
  • Step 4332 Integrate the pixel values in the horizontal direction and the vertical direction on the smoothed image to obtain the first integration curve in the horizontal direction and the second integration curve in the vertical direction, and take the poles of the first integration curve and the second integration curve. set of small value points to determine grid interval lines; and
  • Step 4333 Divide grid regions according to grid spacing lines.
  • box filter smoothing can help to reduce other noise in the image interfering with the image, and then divide the grid area.
  • the length and width of the operator of the box filter satisfy the following conditional expressions:
  • b is the length and width of the box filter operator
  • dist is the region spacing of the region of interest
  • rad is the region radius of the region of interest.
  • the above step 43 includes:
  • Step 434 using the Hough circle transform to detect the region of interest in the deflection corrected image.
  • Step 435 draw a circle according to the detected region of interest to make an approximation to divide it into a grid region.
  • the Hough original transform can also be used to detect the area of interest in the deflection correction image, and then draw a circle according to the detected area of interest to approximate the grid area, so as to achieve Grid area division.
  • division of the grid area may not be limited to the above-discussed embodiments, and other division methods may be used for division as required, which is not specifically limited here.
  • the above step 44 includes:
  • Step 441 traverse the grid area, and obtain the pixel value mean square error for each grid area corresponding to the preprocessed image;
  • Step 442 when the mean square error is greater than the variance threshold, mark the corresponding region of interest sample as positive;
  • Step 443 when the mean square error is not greater than the variance threshold, mark the sample corresponding to the region of interest as negative.
  • the mean square error of the pixel values of each grid is compared with the variance threshold, thereby realizing the division of positive and negative.
  • the method for analyzing the biochip image includes: outputting the positive and negative identification results of the reaction chamber.
  • the method for analyzing biochip images in the embodiments of the present application can realize effective identification of matrix biochip fluorescence images with high throughput and low signal-to-noise ratio.
  • the problem of uneven fluorescence illumination of microchips is solved by high-frequency filtering.
  • the problem of deflection angle detection is solved by the PCA principal component analysis method of the maximum contour of the adjacent same-direction chamber; the periodic pattern prior of the matrix biochip is used, and the surface contamination and sample injection are minimized by constructing a notch filter.
  • the noise caused by the process and the reaction process has successfully realized the automatic analysis of the location of the chamber and the determination of positive and negative samples.

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Abstract

一种芯片装载结构(2)、分析装置(100)及分析系统(300),该芯片装载结构(2)包括装载板体(21),装载板体(21)的内部具有用于容纳检测芯片(1)的容置空间;装载板体(21)的第一板面(2a)上设置有贯通至容置空间的第一镂空区(23)和至少一个第二镂空区(24),其中,第一镂空区(23)用于暴露检测芯片(1)的反应观测区(12);至少一个第二镂空区(24)用于暴露检测芯片(1)的至少一个试剂端口;装载板体(21)上还设置有连接部(27),连接部(27)能够采用可拆卸地方式与分析装置(100)中的用于运送装载板体(21)的输运部(110)连接。

Description

芯片装载结构、分析装置及分析系统 技术领域
本公开的实施例涉及芯片装载结构、分析装置及分析系统。
背景技术
数字聚合酶链式反应芯片技术(dPCR)是将核酸样本充分稀释,使每个反应腔的样本模版数少于或者等于1个,从而实现对单分子DNA的绝对定量。由于其灵敏度高、特异性强、检测通量较高、定量准确等优点而被广泛应用于临床诊断、基因不稳定分析、单细胞基因表达、环境微生物检测和产前诊断等方面。
发明内容
本公开至少一个实施例提供了一种芯片装载结构,其中,包括装载板体,所述装载板体具有用于容纳检测芯片的容置空间;
所述装载板体的第一板面上设置有贯通至所述容置空间的第一镂空区和至少一个第二镂空区,其中,所述第一镂空区用于暴露所述检测芯片的反应观测区;至少一个所述第二镂空区用于暴露所述检测芯片的至少一个试剂端口;
所述装载板体上还设置有连接部,所述连接部能够采用可拆卸地方式与分析装置中的用于运送所述装载板体的输运部连接。
可选的,在所述第一板面上,且位于所述第一镂空区所在位置处设置有第一凹陷部,所述第一凹陷部在所述第一板面上的正投影面积大于所述第一镂空区在所述第一板面上的正投影面积,且所述第一凹陷部在所述第一板面上的正投影完全覆盖所述第一镂空区在所述第一板面上的正投影。
可选的,所述第一镂空区在所述第一板面上的正投影形状包括正方形、矩形或者圆形。
可选的,所述第二镂空区为多个,且沿所述第一板面的第一轴线间隔设置,所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
可选的,在所述第一板面上,且位于每个所述第二镂空区所在位置处均设置有第二凹陷部,所述第二凹陷部在所述第一板面上的正投影面积大于所述第二镂空区在所述第一板面上的正投影面积,且所述第二凹陷部在所述第一板面上的正投影完全覆盖所述第二镂空区在所述第一板面上的正投影。
可选的,在所述装载板体置于所述输运部上时,在所述第一移动方向上靠后的所述第二凹陷部在所述第一板面上的正投影面积大于在所述第一移动方向上靠前的所述第二凹陷部在所述第一板面上的正投影面积;
在所述第一移动方向上靠后的所述第二凹陷部在所述第一板面上的正投影为长圆孔;在所述第一移动方向上靠前的所述第二凹陷部在所述第一板面上的正投影为圆孔。
可选的,所述检测芯片还具有加热电极;所述第一板面上设置有贯通至所述容置空间的第三镂空区,用于暴露所述加热电极。
可选的,所述第三镂空区延伸至所述第一板面的第一侧边;
所述第一侧边与所述第一板面的第一轴线相互垂直;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行,且所述第一侧边为在所述第一移动方向上靠前的侧边。
可选的,在所述装载板体的与所述第一板面相背离的第二板面上设置有容置槽,用以构成所述容置空间,且在所述容置槽的内侧面设置有凸出结构,用以将所述检测芯片限定在所述容置槽中。
可选的,所述凸出结构包括分布在所述第一板面的第一轴线两侧的两组凸部组,每组所述凸部组均包括沿所述第一轴线间隔分布的多个凸部,每个所述凸部自所述容置槽的内侧面朝靠近所述第一轴线的方向凸出,用以与置于所述容置槽中的所述检测芯片的侧面相抵;
所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
可选的,所述凸部在所述第二板面上的正投影形状包括圆弧形。
可选的,所述容置槽延伸至所述第二板面的第二侧边;
所述第二侧边与所述第一板面的第一轴线相互垂直;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行,且所述第二侧边为在所述第一移动方向上靠前的侧边。
可选的,在所述装载本体的位于在所述第一板面的第一轴线两侧的两个侧面上分别设置有插槽组,每组所述插槽组均包括一个或沿所述第一轴线间隔设置的多个插槽,所述插槽用作所述连接部一一对应地与所述输运部中的插接件插接;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
可选的,在所述装载板体的与所述第一板面相背离的第二板面上设置有与所述插槽连通的插口,用以供对应的所述插接件移入或移出所述插槽;并且,在所述插槽的位于其第二轴线一侧的侧面上设置有相对于该侧面朝靠近所述第二轴线的方向凸出的限位凸部,用以在所述插接件移动至所述限位凸部和与之相对的所述插槽的底面之间的间隔位置处时,将所述插接件限定在所述插槽中;所述插槽的第二轴线与所述插接件移入或移出所述插槽的移动方向相互平行。
本公开至少一个实施例还提供了一种分析装置,包括:装载部、输运部、 控温部和信号检测部,其中,
所述装载部采用本公开至少一个实施例提供的上述芯片装载结构,用于承载检测芯片,且能够与所述输运部可拆卸地连接;
所述输运部配置为运送所述芯片装载结构;
所述控温部包括加热器以及冷却器,其中,所述加热器配置为加热所述检测芯片,所述冷却器配置为对所述检测芯片降温;以及
所述信号检测部包括光学传感器,其中,所述光学传感器配置为接收来自所述检测芯片的光并根据所述光进行检测。
可选的,所述输运部包括:
输运结构,配置为承载所述芯片装载结构且可至少部分被驱动;以及
驱动器,配置为能够驱动所述输运结构,以将所述芯片装载结构在第一位置、第二位置和第三位置之间往复移动,
其中,所述第一位置允许将所述芯片装载结构接纳在所述输运结构中;
所述第二位置允许所述控温部调节所述检测芯片的温度;以及
所述第三位置允许所述信号检测部的所述光学传感器接收来自所述检测芯片的所述光。
可选的,所述输运结构包括:
载物台,配置为在使用中承载所述芯片装载结构;
可移动平台,配置为与所述驱动器连接,以在所述驱动器的驱动下进行移动;以及
支架,配置为连接所述载物台和所述可移动平台,由此使得当可移动平台被驱动时可以带动载物台。
可选的,所述装载部采用本公开至少一个实施例提供的上述芯片装载结构;
在所述载物台的承载面上设置有用于容纳所述装载板体的安装槽,且在 所述载物台的第一侧面设置有与所述安装槽连通的安装槽开口,用以供所述装载板体移入或移出所述安装槽,所述第一侧面与所述载物台移入所述分析装置内部的第一移动方向相互垂直,且为在所述第一移动方向上朝后的侧面;
并且,在所述载物台上还设置有自所述安装槽的侧面朝靠近所述安装槽的第三轴线的方向凸出的所述插接件;所述第三轴线与所述第一移动方向相互平行。
可选的,所述装载部采用本公开至少一个实施例提供的上述芯片装载结构;
所述加热器包括至少一个接触电极,至少一个所述接触电极配置为在使用中一一对应地与所述检测芯片的至少一个所述加热电极电接触;
所述加热器还配置为通过所述接触电极向所述检测芯片的所述加热电极施加电信号,以使所述加热电极加热所述检测芯片。
可选的,所述接触电极固定在所述载物台的承载面上,且位于所述安装槽的与所述安装槽开口相对的一侧,并且所述接触电极的一端相对于所述安装槽的侧面沿与所述载物台移入所述分析装置内的第一移动方向相反的方向凸出;
所述接触电极设置有用于与所述加热电极电接触的接触部,所述接触部相对于所述接触电极的与所述加热电极相对的表面,朝靠近所述加热电极的方向凸出;并且,所述加热器还包括弹性件,所述弹性件分别与所述接触电极和所述载物台连接,用以向所述接触电极施加朝向所述载物台的承载面的拉力。
可选的,所述弹性件包括弹簧。
可选的,在所述载物台的承载面上设置有电极插槽,所述接触电极插设在所述电极插槽中,并且所述接触电极与所述载物台通过紧固件固定连接。
可选的,所述信号检测部还包括:
光源,配置为在使用中提供光以照射所述检测芯片;
光传输部,配置为在使用中将所述光源提供的所述光传输至所述检测芯片以及将由所述检测芯片发出的光传输至所述光学传感器;以及
托架,用于固定和承载所述光源和所述光传输部,且在所述托架上还设置有焦距调节结构,所述焦距调节结构配置为调节所述光传输部与所述检测芯片之间的距离,以使所述检测芯片位于所述光传输部的焦点处;并且,所述焦距调节结构具有焦距调节旋钮以及与所述焦距调节旋钮连接的旋钮延长部,所述旋钮延长部延伸至靠近所述光传输部的一侧,以便于人工调节。
本公开至少一个实施例还提供了一种分析系统,包括:
本公开至少一个实施例提供的上述分析装置;以及
所述检测芯片。
附图说明
为了更清楚地说明本公开实施例的技术方案,下面将对实施例的附图作简单地介绍,显而易见地,下面描述中的附图仅仅涉及本公开的一些实施例,而非对本公开的限制。
图1是根据本公开至少一个实施例的检测芯片的示意性框图。
图2A是根据本公开至少一个实施例的芯片装载结构的正面结构图。
图2B是根据本公开至少一个实施例的芯片装载结构的背面结构图。
图2C是根据本公开至少一个实施例的芯片装载结构的立体结构图。
图2D是根据本公开至少一个实施例的芯片装载结构在承载检测芯片时的立体结构图。
图2E是根据本公开至少一个实施例的另一种芯片装载结构的正面结构图。
图2F是根据本公开至少一个实施例的另一种芯片装载结构的背面结构图。
图3是根据本公开至少一个实施例的分析装置的示意性框图。
图4是根据本公开至少一个实施例的输运部的示意性框图。
图5A是根据本公开至少一个实施例的输运结构的分解状态的结构图。
图5B是根据本公开至少一个实施例的输运结构的组装状态的结构图。
图6A是根据本公开至少一个实施例的载物台的正面结构图。
图6B是根据本公开至少一个实施例的载物台的背面结构图。
图6C是根据本公开至少一个实施例的载物台的立体结构图。
图6D是根据本公开至少一个实施例的接触电极和弹簧件的结构图。
图6E是根据本公开至少一个实施例的载物台在承载装载板体时的结构图。
图7A是根据本公开至少一个实施例的控温部的分解状态的结构示意图。
图7B是根据本公开至少一个实施例的控温部的组装状态的结构图。
图8是根据本公开至少一个实施例的信号检测部的示意性框图。
图9A是根据本公开至少一个实施例的信号检测部的一侧视图。
图9B是根据本公开至少一个实施例的信号检测部的另一侧视图。
图10是根据本公开至少一个实施例的分析装置的内部整机结构图。
图11A是根据本公开至少一个实施例的分析装置的外部整机结构图。
图11B是根据本公开至少一个实施例的分析装置的外部正面视图。
图11C是根据本公开至少一个实施例的分析装置的外部背面视图。
图11D是根据本公开至少一个实施例的分析装置的一外部侧面视图。
图11E是根据本公开至少一个实施例的分析装置的另一外部侧面视图。
图11F是根据本公开至少一个实施例的分析装置在控制阀门开启时的另一外部侧面视图。
图11G是根据本公开至少一个实施例的分析装置的外部底面视图。
图12A是根据本公开至少一个实施例的分析装置在装载阀门开启时的状态图。
图12B是根据本公开至少一个实施例的分析装置在装载板体位于第一位置时的状态图。
图12C是根据本公开至少一个实施例的分析装置在装载板体位于第二位置时的状态图。
图12D是根据本公开至少一个实施例的分析装置在装载板体位于第三位置时的状态图。
图13是根据本公开至少一个实施例的分析系统的示意性框图。
图14是根据本公开至少一个实施例的控温循环的温度变化图。
图15是本申请实施方式的对分割的反应腔室进行膨胀处理后的轮廓示意图。
图16是本申请实施方式的生物芯片图像傅里叶变换到频域的幅值示意图。
图17是本申请实施方式的构建滤波器的示意图。
具体实施方式
为了使得本公开实施例的目的、技术方案和优点更加清楚,下面将结合本公开实施例的附图,对本公开实施例的技术方案进行清楚、完整地描述。显然,所描述的实施例是本公开的一部分实施例,而不是全部的实施例。基于所描述的本公开的实施例,本领域普通技术人员在无需创造性劳动的前提下所获得的所有其他实施例,都属于本公开保护的范围。
除非另外定义,本公开使用的技术术语或者科学术语应当为本公开所属领域内具有一般技能的人士所理解的通常意义。本公开中使用的“第一”、“第二”以及类似的词语并不表示任何顺序、数量或者重要性,而只是用来区分不同的组成部分。“包括”或者“包含”等类似的词语意指出现该词前面的元件或者物件涵盖出现在该词后面列举的元件或者物件及其等同,而不排除其他元件或者物件。“连接”或者“相连”等类似的词语并非限定于物理的或者机械的连接,而是可以包括电性的连接,不管是直接的还是间接的。“上”、“下”、“左”、“右”等仅用于表示相对位置关系,当被描述对象的绝对位置改变后,则该相对位置关系也可能相应地改变。
为了保持本公开实施例的以下说明清楚且简明,本公开省略了已知功能和已知部件的详细说明。
一些dPCR产品通常需要多台配套设备,以得出分析结果,这导致 检测时间长、检测成本高、操作步骤多以及存在试剂污染的风险。
本公开的至少一个实施例提供了一种芯片装载结构、分析装置及分析系统,该实施例的分析装置整合、集成了装载部、控温部和信号检测部,以单台设备实现对于检测芯片的检测,减少了所需的配套设备的数量、简化了操作步骤、缩短了检测时间、并且减小了试剂污染的风险。此外,通过借助上述芯片装载结构承载检测芯片,并能够采用可拆卸地方式与分析装置中的输运部连接,既可以起到保护检测芯片的作用,减少检测芯片在放入输运部的过程中被损坏的风险,又可以简化检测芯片安装在输运部上的装卸载过程,提高检测芯片的安装便捷性。
图1是根据本公开至少一个实施例的检测芯片的示意性框图。如图1所示,检测芯片1的一面具有反应观测区12,例如,对于数字聚合酶链式反应芯片(dPCR)等的微流控芯片,该反应观测区12例如为微孔反应腔室阵列区域。并且,检测芯片1还具有加热电极11,该加热电极11例如呈矩形板状。在接收到电信号的情况下,加热电极11或与其电连接的电阻走线等的部件可产生热量,以加热检测芯片1。当然,在实际应用中,根据类型的不同,也有不设置加热电极的检测芯片1。另外,检测芯片1还可以包括其他用途的电极,例如用于施加电信号以驱动样品在检测芯片1中移动的电极等;如上所述,本公开的实施例对于检测芯片1的类型、结构等不作限制。
应理解,本公开的各实施例中描述的检测芯片1可以是任何类型的生物检测芯片或化学检测芯片,例如各种微流控芯片,本公开的实施例对此不作限制。
图2A是根据本公开至少一个实施例的芯片装载结构的正面结构图。图2B是根据本公开至少一个实施例的芯片装载结构的背面结构图。 图2C是根据本公开至少一个实施例的芯片装载结构的立体结构图。请一并参阅图2A至图2B,根据本公开至少一个示例的芯片装载结构2,其能够采用可拆卸地方式与分析装置中的输运部连接,既可以起到保护检测芯片1的作用,减少检测芯片1在放入输运部的过程中被损坏的风险,又可以简化检测芯片1安装在输运部上的装卸载过程,提高检测芯片1的安装便捷性。
具体地,芯片装载结构2包括装载板体21,其例如采用矩形板体,且可选的,采用耐高温材料制作,以保证在对检测芯片1进行加热时不会发生变形。该装载板体21在整体上为一矩形盒体,其轮廓通常与检测芯片1的外形基本相同。并且,装载板体21具有用于容纳检测芯片1的容置空间,例如,如图2D所示,此时检测芯片1位于上述容置空间中。
并且,如图2A所示,装载板体21的第一板面2a上设置有贯通至上述容置空间的第一镂空区23和至少一个第二镂空区24,例如,图2A和图2B中示出了两个第二镂空区24。其中,第一镂空区23用于暴露检测芯片1的反应观测区12;各个第二镂空区24用于暴露检测芯片1的各个试剂端口(图中未示出)。可选的,如图2C所示,在装载板体21的第一板面2a上还可以在上述第一镂空区23所在位置处设置第一凹陷部231,该第一凹陷部231在第一板面2a上的正投影面积大于第一镂空区23在第一板面2a上的正投影面积,且第一凹陷部231在第一板面2a上的正投影完全覆盖第一镂空区23在第一板面2a上的正投影。第一凹陷部231的设置,可以扩大观测视野。
在一些实施例中,可选的,第一镂空区23在第一板面2a上的正投影形状包括正方形、矩形或者圆形。例如,图2A示出的第一镂空区23 在第一板面2a上的正投影形状为正方形。又如,如图2E所示,本公开的实施例还提供了另一种芯片装载结构2’,其装载板体21’的第一板面2a’上设置有第一镂空区23’,该第一镂空区23’在第一板面2a’上的正投影形状为圆形。需要说明的是,在实际应用中,可以为不同类型、结构的检测芯片1配备相应的芯片装载结构。
在一些实施例中,可选的,第二镂空区24为多个,且沿第一板面2a的第一轴线间隔设置,该第一轴线在装载板体21置于上述输运部上时的方向,与该输运部移入上述分析装置内部的第一移动方向(即,图2A示出的X方向)相互平行。例如,图2A和图2B中示出了两个第二镂空区24,二者沿X方向间隔设置,且分别位于第一镂空区23的两侧。当然,在实际应用中,两个第二镂空区24也可以位于第一镂空区23的同一侧。
在一些实施例中,可选的,如图2C所示,在装载板体21的第一板面2a上还可以在每个第二镂空区24所在位置处设置第二凹陷部241,该第二凹陷部241在第一板面2a上的正投影面积大于第二镂空区24在第一板面2a上的正投影面积,且第二凹陷部241在第一板面2a上的正投影完全覆盖第二镂空区24在第一板面2a上的正投影。第二凹陷部241的设置可以在填充或排出试剂时避免试剂漏出。
在一些实施例中,可选的,如图2A所示,在装载板体21置于上述输运部上时,在第一移动方向(即,图2A示出的X方向)上靠后的第二凹陷部241在第一板面2a上的正投影面积大于在上述第一移动方向上靠前的第二凹陷部241在第一板面2a上的正投影面积,这样设置是因为:对于某些检测芯片,例如图1示出的检测芯片1,其多个试剂端口中的试剂填充口一般位于在第一移动方向(即,图2A示出的X方向) 上靠后的位置处,而试剂排出口一般位于在第一移动方向(即,图2A示出的X方向)上靠前的位置处,并且在填充试剂时,试剂填充口相较于试剂排出口更容易泄漏,故而通过适当增大将与试剂填充口对应的第二凹陷部241在第一板面2a上的正投影面积,可以进一步避免试剂漏出。可选的,在上述第一移动方向上靠后的第二凹陷部241在第一板面2a上的正投影为长圆形;在第一移动方向上靠前的第二凹陷部241在第一板面2a上的正投影为圆形。
在本公开的实施例中,检测芯片1还具有加热电极11,为了能够使之与加热器中的接触电极(在下文中具体描述)电接触,如图2D所示,装载板体21的第一板面2a上设置有贯通至上述容置空间的第三镂空区22,用于暴露加热电极11。这样,上述接触电极可以自装载板体21的第一板面2a一侧通过第三镂空区22与加热电极11电接触。可选的,如图2D所示,为了便于第三镂空区22与加热电极11电接触,第三镂空区22延伸至装载板体21的第一侧边,该第一侧边与第一板面2a的第一轴线相互垂直;该第一轴线在装载板体21置于上述输运部上时的方向,与上述第一移动方向(即,图2D示出的X方向)相互平行,且该第一侧边为在上述第一移动方向上靠前的侧边。
需要说明的是,本公开的实施例还提供了另一种芯片装载结构2’,其在装载板体21’的第一板面2a’上同样设置有第二镂空区24’和第三镂空区22’,由于其与上述第二镂空区24和第三镂空区22的设置方式相同,在此不再赘述。
还需要说明的是,在实际应用中,根据类型的不同,检测芯片1的试剂端口的数量和位置也可能不同。本公开的实施例中的第二镂空区24的数量和位置可以根据检测芯片1的试剂端口的数量和位置作适应性设 计。另外,根据不同类型的检测芯片1,在装载板体21的第一板面2a上还可以设置其他功能的镂空区,本公开的实施例对此没有限制。
在本公开的一些实施例中,上述容置空间的构成结构可以有多种,例如,如图2B所示,在装载板体21的与第一板面2a相背离的第二板面2b上设置有容置槽25,用以构成上述容置空间,由于该容置槽25在第二板面2b上是敞开的,以使检测芯片1能够从第二板面2b一侧移入或移出容置槽25,同时,敞开的容置槽25有助于提高对检测芯片1的冷却效率,同时还可以避免装载板体21的温度过高。并且,在容置槽25的内侧面设置有凸出结构,用以将检测芯片1限定在容置槽25中。
上述凸出结构可以有多种结构,例如,如图2B所示,该凸出结构包括分布在第一板面2a的上述第一轴线(平行于X方向)两侧的两组凸部组,每组凸部组均包括沿上述第一轴线间隔分布的多个凸部26,每个凸部26自容置槽25的内侧面朝靠近上述第一轴线的方向凸出,用以与置于容置槽25中的检测芯片1的侧面相抵,从而可以在摩擦力的作用下将检测芯片1固定在容置槽25中。这种凸出结构不仅可以减少与检测芯片1的接触面积,以便于检测芯片1的安装,而且由于两组凸部组是在检测芯片1的两侧夹持固定检测芯片1,这可以保证固定的稳固性。可选的,为了避免检测芯片1与凸部26发生剐蹭和磨损,将凸部26在第二板面2b上的正投影形状设计为诸如半圆形或者半椭圆形等的圆弧形。
在一些实施例中,可选的,容置槽26延伸至第二板面2b的第二侧边;该第二侧边与上述第一轴线(平行于X方向)相互垂直,且该第二侧边为在上述第一移动方向上靠前的侧边。这样,对于设置有加热电极11的检测芯片1,在装载板体21置于上述输运部上时,加热电极11能 够与输运部上的接触电极的位置相对应,以实现二者的接触连接。
需要说明的是,本公开的实施例还提供了另一种芯片装载结构2’,其在装载板体21’的第二板面2b’上同样设置有容置槽25’和凸部26’,由于其与上述容置槽25和凸部26的设置方式相同,在此不再赘述。
在本公开的一些实施例中,,如图2B和图2C所示,装载板体21上还设置有连接部27,该连接部27能够采用可拆卸地方式与分析装置中的用于运送装载板体21的输运部连接。也就是说,检测芯片1不是直接安装在输运部上,而是借助装载板体21安装在输运部上,这样,既可以起到保护检测芯片1的作用,减少检测芯片1在放入输运部的过程中被损坏的风险,又可以简化检测芯片1安装在输运部上的装卸载过程,提高检测芯片1的安装便捷性。
上述连接部27例如可以采用插接的方式与上述输运部连接,具体地,如图2B和图2C所示,在装载板体21的位于上述第一轴线(即,平行于X方向)的两个侧面2c上分别设置有插槽组,每组插槽组均包括一个或沿第一轴线间隔设置的多个插槽,该插槽用作上述连接部27,例如,如图2C所示,设置在每个侧面2c上的插槽组中均包括两个插槽(即,连接部27),且各个插槽一一对应地与上述输运部中的插接件(在下文中描述)插接,从而实现将装载板体21可拆卸地固定在输运部上,同时这种插接方式非常便捷,简化了检测芯片1安装在输运部上的装卸载过程,提高了安装效率。当然,在实际应用中,还可以采用诸如卡接、机械固定等其他任意可拆卸地方式将连接部27与上述输运部连接。
在本公开的一些实施例中,可选的,如图2B所示,在装载板体21的与第一板面2a相背离的第二板面2b上设置有与上述插槽连通的插口,用以供对应的上述插接件移入或移出该插槽,例如,如图2C所示, 上述插槽的插口朝下,插接件可以沿Y方向经过该插口移入或移出插槽。并且,在上述插槽的位于其第二轴线(平行于上述Y方向)一侧的侧面上设置有相对于该侧面朝靠近该第二轴线的方向凸出的限位凸部271,用以在位于插槽中的插接件相对于装载板体21移动至与限位凸部271和与之相对的插槽的底面之间的间隔位置处时,将插接件限定在插槽中。
在需要安装装载板体21时,如图2C所示,首先沿Y方向向下移动装载板体21,以将插接件沿Y方向经过该插口移入插槽中,然后沿Z方向向右平移装载板体21,以将插接件沿Z方向向左平移至限位凸部271的上方,即移动至限位凸部271和与之相对的插槽的底面之间的间隔位置处,此时在限位凸部271与插接件相配合的作用下,装载板体21无法沿Y方向移动,即实现将装载板体21固定在上述输运部上。反之,在需要卸载装载板体21时,首先沿Z方向向左平移装载板体21,以将插接件沿Z方向向右平移至与限位凸部271相互错开,并与插口相对的位置处;然后沿Y方向向上移动装载板体21,以将插接件沿Y方向经过该插口移出插槽,此时装载板体21可以沿Y方向移动,即实现将装载板体21自上述输运部卸载。
需要说明的是,本公开的实施例还提供了另一种芯片装载结构2’,其在装载板体21’的第二板面2b’上同样设置有连接部27’,由于其与上述连接部27的设置方式相同,在此不再赘述。
本公开至少一个实施例还提供了一种分析装置,图3是根据本公开至少一个实施例的分析装置的示意性框图。如图3所示,根据本公开至少一个示例的分析装置100至少可包括装载部140、输运部110、控温部120和信号检测部130。
输运部110采用本公开至少一个实施例提供的上述芯片装载结构,用于承载检测芯片1,且能够与输运部110可拆卸地连接。
输运部配置为运送所述芯片装载结构输运部110配置为在使用中接收并承载上述芯片装载结构中的装载板体21(承载有检测芯片1),并允许将装载板体21移动至控温部120和信号检测部130。
控温部120包括加热器121以及冷却器122。加热器121配置为加热装载到分析装置中的检测芯片1(由装载板体21承载),冷却器122配置为对装载到分析装置中的检测芯片1降温,由此实现对于检测芯片1的温度的控制。
信号检测部130包括光学传感器131。光学传感器131配置为接收来自检测芯片1的光,并根据检测芯片1的光进行检测。
图4是根据本公开至少一个实施例的输运部的示意性框图。输运部110可包括输运结构111和驱动器112。
输运结构111配置为承载上述芯片装载结构(即,装载板体21),且可至少部分被驱动。驱动器112配置为能够驱动输运结构111,例如可操作地与输运结构111连接,将上述芯片装载结构(即,装载板体21)在第一位置、第二位置和第三位置之间往复移动。在至少一个实施例中,第一位置允许将上述芯片装载结构(即,装载板体21)接纳在输运结构111中,即允许用户将装载板体21放入至输运部110中,由该装载板体21承载加载了检测样本的检测芯片1。第二位置允许控温部120调节检测芯片1的温度。第三位置允许信号检测部130的光学传感器131接收来自检测芯片1的光。例如,在下文中将描述的图12B中示出了本公开至少一个实施例中的第一位置的示例。例如,在下文中将描述的图12C中示出了本公开至少一个实施例中的第二位置的示例。例如,在下文中 将描述的图12D中示出了本公开至少一个实施例中的第三位置的示例。
然而,应理解,在一些实施例中,输运部110也可不包括驱动器112,从而可手动地移动(例如推动或拉动)输运结构111,本公开的实施例对此不作限制。
图5A是根据本公开至少一个实施例的输运结构的分解状态的结构图,以及图5B是根据本公开至少一个实施例的输运结构的组装状态的结构图。如图5A和图5B所示,输运结构111可包括载物台1111、可移动平台1112和支架1113。
载物台1111配置为在使用中承载上述芯片装载结构(即,装载板体21),在图6A至图6E所示的示例中,载物台1111为矩形的板状,能够可移动地安装在支架1113上(如图5B所示)。图6A是根据本公开至少一个实施例的载物台的正面结构图。如图6A所示,载物台1111可以采用插接的方式与上述芯片装载结构中的装载板体21上的连接部27连接,具体地,在载物台1111的承载面1111a上设置有用于容纳上述装载板体21的安装槽31,且在该载物台1111的第一侧面设置有与该安装槽31连通的安装槽开口31a,用以供装载板体21移入或移出安装槽31中,如图6A所示,该第一侧面与载物台1111移入分析装置内部的第一移动方向(即,图6A示出的X方向)相互垂直,且为在上述第一移动方向上朝后的侧面。
并且,在载物台1111上还设置有相对于该安装槽31的侧面朝靠近安装槽31的第三轴线(与X方向平行)的方向凸出的插接件32。结合图2C和图6E所示,插接件32相对于安装槽31的侧面凸出的部分能够从插口沿Y方向移入或移出插槽(即,连接部27)。应理解,借助安装槽开口31a,可以允许置于安装槽31中的装载板体21沿X方向平移, 以能够使插接件32沿图2C所示的Z方向向右或向左平移。由于插接件32与上述插槽的插接方式在上文中已有了详细描述,在此不再赘述。
在本公开的一些实施例中,可选的,载物台1111可通过耐高温材料形成,该耐高温材料例如可以是金属、塑料、陶瓷、橡胶、树脂等。形成载物台1111的耐高温材料的热变形温度例如可在100℃、200℃、300℃、400℃、500℃以上。载物台1111还可通过耐高温且导热性差的材料形成。例如,在一个具体实施例中,载物台1111可通过陶瓷形成,从而既具有较轻的重量,又能够耐高温。
在本公开的一些实施例中,图6B是根据本公开至少一个实施例的载物台的背面结构图。如图6B所示,在载物台1111中设置有自其背面1111b贯通至承载面1111a的四个通孔36,用于利用紧固件(例如螺钉或螺栓)将载物台1111与支架1113固定连接。可选的,在载物台1111与支架1113之间可通过四个压缩弹簧连接,用以朝向二者施加使彼此远离的弹力,利用压缩弹簧的弹性作用,可以通过旋紧或旋松紧固件,来调节载物台1111与支架1113之间的间距,从而可以调节载物台1111的水平度。可选的,上述四个压缩弹簧可以套设在上述紧固件上。当然,在实际应用中,还可以通过设置其他调平结构对载物台1111的水平度进行调节,本公开的实施例对此不作限制。
可选的,载物台1111还可包括水平仪,以检测载物台1111是否水平。水平仪可通过粘合剂等粘附至载物台1111,本公开的实施例对此不作限制。水平仪例如可以是气泡水平仪、电感式水平仪、电容式水平仪等,本公开的实施例对此不作限制。通过水平仪,可以检测载物台1111是否水平,并根据检测结果利用上述调平结构对载物台1111的水平度进行调节,从而可以提高调平的准确度,使得承载在载物台1111上检 测芯片1(由装载板体21承载)保持水平,从而有助于光学传感器131接收来自检测芯片1的光。
如图6A所示,载物台1111可具有镂空区34,使得在装载板体21置于载物台1111上时,将装载板体21与载物台1111的接触面至少部分地暴露,例如暴露给控温部120的冷却器122。可选的,如图2B所示,由于装载板体21上的容置槽25在第二板面2b上是敞开的,故而使装载板体21承载的检测芯片1可以暴露给控温部120的冷却器122,从而可以提高对检测芯片1的冷却效率。根据实际要求,镂空区34可具有任何合适的形状,例如圆形、三角形、矩形、五边形、六边形或其他不规则形状等;又例如,镂空区34可以具有一个或多个开口,本公开的实施例对此不作限制。装载板体21在镂空区34所在平面上的投影的大小大于镂空区34的大小,以使得装载板体21不会自镂空区34脱离载物台1111。
在本公开的一些实施例中,如图6D所示,加热器121可包括至少一个接触电极33,该接触电极33例如可通过耐高温金属材料形成。至少一个接触电极33配置为在使用中一一对应地与检测芯片1的至少一个加热电极11电接触。加热器121还配置为通过接触电极33向检测芯片1的加热电极11施加电信号,以使加热电极11加热检测芯片1。
在本公开的一些实施例中,如图6C所示,接触电极33固定在载物台1111的承载面1111a上,且位于与安装槽开口31a相对的一侧,并且接触电极33的一端相对于安装槽31的侧面沿与X方向相反的方向凸出,即,接触电极33自安装槽31的一侧延伸至安装槽31的内部,以允许在使用中与检测芯片1的暴露的加热电极11电接触,从而向检测芯片1的加热电极11施加电信号(例如直流电压或交流电压)。当检测 芯片1放置在载物台1111上后,接触电极33与检测芯片1的加热电极11电接触,从而可以传输电信号。接触电极33可通过穿过载物台1111的线路与电源或控制器电连接,以接收控制信号。
可选的,接触电极33上设置有用于与加热电极11电接触的接触部331,该接触部331相对于接触电极33的与加热电极11相对的表面,朝靠近该加热电极11的方向凸出,例如,如图6D所示,该接触部331为由接触电极33的一端弯折形成的凸部,该凸部优选与接触电极33之间呈锐角,以便于检测芯片1的加热电极11插入至接触电极33的内侧。通过使接触部331相对于接触电极33的与加热电极11相对的表面凸出,可以在装载板体21放置在载物台1111上后,使接触电极33因受到装载板体21的挤压而产生一定程度的弹性变形,从而可以使接触电极33与加热电极11保持紧密接触,以实现良好的电接触。并且,如图6D所示,加热器121还包括弹性件35,该弹性件35分别与接触电极33和载物台1111连接,用以向接触电极33施加朝向载物台1111的承载面1111a的拉力。借助弹性件35,既可以实现接触电极33与载物台1111的弹性连接,又可以在装载板体21移出安装槽31时,使接触电极33复位。可选的,上述弹性件35为弹簧,例如为拉伸弹簧。进一步的,可以在接触电极33上设置限位槽333,用以限定弹性件35在接触电极33上的位置。
此外,可选的,如图6C所示,在载物台1111的承载面1111a上设置有电极插槽312,接触电极33插设在该电极插槽312中,并且接触电极33与载物台1111通过紧固件固定连接,例如,如图6D所示,可以在接触电极33的远离接触部331的一端设置安装孔332,并通过紧固件(例如螺钉或螺栓)与载物台1111固定连接。
可选的,如图6A所示,在安装槽31的与安装槽开口31a相对的侧面的两个边角处还设置有限位台阶311,用以限定装载板体21在安装槽31中的位置,同时能够为其承载的检测芯片1的加热电极11以及接触电极33预留一定的接触空间。
在另一些实施例中,检测芯片1可不具有加热电极,并且加热器121可配置为向检测芯片1提供加热用红外线或气流,以加热检测芯片1。例如加热器121可以是红外线加热器或气体加热器(例如通过电阻加热空气以及通过风扇驱动加热后的空气流动)等,本公开的实施例对此不作限制。
可移动平台1112配置为与驱动器112可操作地连接,以在驱动器112的驱动下进行移动。驱动器112例如可以是电机,可移动平台1112例如与电机的驱动端连接。例如,如图5A和图5B所示,驱动器112可以是旋转电机,该旋转电机的驱动端与丝杠S连接,从而可以转动丝杠S,可移动平台1112通过与丝杠S螺纹啮合的螺母与丝杠S连接,从而可以将丝杠S的转动转化为水平移动,使得可移动平台1112可通过驱动器112的驱动而移动。此外,还可设置有平行于丝杠S的导引杆G。可移动平台1112可移动地连接至导引杆G。导引杆G起到约束可移动平台1112的作用。应理解,图5A和图5B中示出的导引杆G和丝杠S的数量均是示例性的,本公开的实施例对此不作限制。例如,驱动器112可以是直线电机,该直线电机的动子可与可移动平台1112连接,从而驱动可移动平台1112移动。本公开的实施例对于驱动器112如何驱动可移动平台1112不作限制,例如,还可以通过齿轮齿条组合以将旋转运动转化为水平移动。
可移动平台1112可通过任何刚性材料形成,例如,金属、塑料、 陶瓷、橡胶、树脂等,本公开的实施例对此不作限制。此外,应理解,图5A和图5B中示出的可移动平台1112的形状也仅是示例性的,根据实际要求,可移动平台1112可具有任何合适的形状。
支架1113配置为连接载物台1111和可移动平台1112,由此使得当可移动平台1112被驱动时可以带动载物台1111。
如图5A中的虚线框所示,支架1113可包括第一部分1113A和第二部分1113B。第一部分1113A配置为在使用中承载载物台1111。第二部分1113B配置为在使用中连接至可移动平台1112。第一部分1113A沿第一方向延伸,第二部分1113B沿第二方向延伸,并且第一方向与第二方向垂直。将支架1113形成为L形或T形,从而减小在单一方向上的尺寸,有助于减小分析装置的整体体积。
支架1113的第一部分1113A例如可通过弹簧等与载物台1111连接,例如通过与载物台1111的四个角落对应的四个弹簧,从而通过调节相应的弹簧可调节载物台1111的水平状态。
支架1113的第二部分1113B例如可通过螺丝等与可移动平台1112可拆卸地连接或固定连接,以允许可移动平台1112带动支架1113一起移动。或者,第二部分1113B可以与可移动平台1112一体形成。
支架1113可通过任何刚性材料形成,例如,金属、塑料、陶瓷、橡胶、树脂等,本公开的实施例对此不作限制。此外,应理解,图5A和图5B中示出的支架1113的形状也仅是示例性的,根据实际要求,支架1113可具有任何合适的形状。
图7A是根据本公开至少一个实施例的控温部的分解状态的结构示意图。图7B是根据本公开至少一个实施例的控温部的组装状态的结构图。如图7A和图7B所示,控温部120例如可包括温度传感器123。温 度传感器123配置为检测检测芯片1的温度。温度传感器123可采用常规的温度传感器,本公开的实施例对此将不再赘述。例如,温度传感器123可包括红外温度传感器或热电偶温度传感器。应理解,在本公开的一些实施例中,若检测芯片1包括温度传感器,则分析装置中无需再设置温度传感器123。
如图7B所示,温度传感器123和冷却器122配置为彼此间隔,以允许将检测芯片1夹设在温度传感器123与冷却器122之间。如图7A和图7B所示,控温部120还可包括控温支架124,温度传感器123和冷却器122与控温支架124连接,以彼此间隔开。应理解,图7A和图7B中温度传感器123和冷却器122的位置仅是示例性的,本公开的实施例对此不作限制。例如,在另一些实施例中,温度传感器123在使用中可在检测芯片1的上方或下方,而冷却器122在使用中可在检测芯片1的侧部。
例如,冷却器122可包括但不限于风扇或半导体制冷片,本公开的实施例对冷却器122的具体类型不作限制。如图7B所示,冷却器122可示例性地为风扇,该风扇外形大致为圆形并且通过设置在四个角上的四个安装柱122a固定在控温支架124中。具体地,如图7A所示,在控温支架124的底座上设置有四个通孔124a,用以通过螺钉一一对应地使四个安装柱122a安装在控温支架124的底座上。
如图7A和图7B所示,控温支架124由底板和设置在该底板上的竖直板和水平板组成,该水平板相对设置在底板的上方,并由竖直板支撑,冷却器122由底板支撑,温度传感器123设置在水平板上,并相对位于冷却器122的上方。当检测芯片1在使用中位于温度传感器123和冷却器122之间时,温度传感器123能够检测检测芯片1的温度;冷却 器122能够对检测芯片1降温。
可选的,如图7A所示,在上述水平板和竖直板的夹角处还设置有肋板124b,用以加强水平板和竖直板的连接稳定性。该肋板124b垂直于上述水平板和竖直板,且两个侧面呈直角,以能够分别与上述水平板和竖直板贴合,并且肋板124b还具有波浪状侧面,用以为冷却器122提供安装空间。
控温支架124可通过任何刚性材料形成,例如,金属、塑料、陶瓷、橡胶、树脂等,本公开的实施例对此不作限制。此外,应理解,图7A和图7B中示出的控温支架124的形状也仅是示例性的,根据实际要求,控温支架124可具有任何合适的形状。
图8是根据本公开至少一个实施例的信号检测部的示意性框图。如图8所示,在本公开的至少一个实施例中,除光学传感器131之外,信号检测部130还可包括光源132和光传输部133。
光学传感器131例如为图像传感器,以配置为采集检测芯片的图像(例如生物芯片图像)以用于分析。例如光学传感器131可以包括电荷耦合器件(CCD)或互补金属氧化物半导体(CMOS)。然而,应理解,在其他实施例中,光学传感器131还可以是光电二极管、光敏电阻、红外线传感器、紫外线传感器等,本公开的实施例对此不作限制。
光源132可配置为在使用中提供光以照射检测芯片。光传输部133可配置为在使用中将光源132提供的光传输至检测芯片以及将由检测芯片发出的光传输至光学传感器131。
例如,光源132可为多种类型可以发射可见光、红外线等,例如包括激光器或荧光光源,激光器和荧光光源的波长可根据实际需要进行选择,本公开的实施例对此不作限制。
图9A是根据本公开至少一个实施例的信号检测部的一侧视图。图9B是根据本公开至少一个实施例的信号检测部的另一侧视图。如图9A和图9B所示,在本公开的一些实施例中,光传输部133可包括90°转向棱镜系统1331和反射光路系统1332。90°转向棱镜系统1331可配置为将来自检测芯片的光传输至光学传感器131。反射光路系统1332可配置为传输来自光源132的光,以照射检测芯片,并且反射光路系统1332还可包括滤光片,该滤光片在从检测芯片到光学传感器131的光路上,以对该光路上传输的光进行过滤,仅允许设定波长的光透过。90°转向棱镜系统1331和反射光路系统1332均可采用本领域中的常规设计,本公开对此将不再赘述。
如图9A和图9B所示,在一些实施例中,信号检测部130还可包括物镜134。物镜134配置为采集来自检测芯片的光。例如,物镜134可包括透镜。
如图9A和图9B所示,在一些实施例中,信号检测部130还可包括托架135。托架135用于固定和承载信息检测部130中的至少部分部件,如光源132、光传输部133等。在一些实施例中,托架135上还设置有焦距调节结构,该焦距调节结构配置为调节光传输部133与检测芯片之间的距离,以使得检测芯片处于光传输部133的焦点处。并且,如图9B所示,焦距调节结构具有焦距调节旋钮136以及与该焦距调节旋钮136连接的旋钮延长部1361,该旋钮延长部1361延伸至靠近光传输部133的一侧,以便于人工调节。托架135可采用本领域中的常规设计,本公开对此将不再赘述。
在一些实施例中,信号检测部130还可包括水平仪(图中未示出),以检测信号检测部130是否水平。例如,水平仪可连接至光传输部133、 光学传感器131、光源132等。作为示例,水平仪可连接至90°转向棱镜系统1331。然而,应理解,本公开的实施例并不限于此。水平仪通过任何适合方式连接至信号检测部130的其他部件,例如粘接、磁性吸附、螺纹连接等,本公开的实施例对此不作限制。水平仪例如可以是气泡水平仪、电感式水平仪、电容式水平仪等,本公开的实施例对此不作限制。通过水平仪例如可使得从光传输部133传输至检测芯片的光垂直于检测芯片或者来自检测芯片的光垂直地进入光传输部133,从而便于后续的信号处理,例如可省略对检测芯片的图像进行角度校正的步骤。
图10是根据本公开至少一个实施例的分析装置的内部整机结构图。如图10所示,分析装置可包括底座101,并且输运部110、控温部120和信号检测部130均设置在底座101上,例如通过螺钉、夹具、粘合剂等固定在底座101上。控温部120和信号检测部130可沿输运部110中的可移动平台1112的移动路径设置,以使得通过可移动平台1112的移动可带动承载在载物台1111上的装载板体21移动至控温部120处进行温度控制和移动至信号检测部130处以采集来自检测芯片的光。
然而,应理解,图10所示的布置方式进行示例性的,根据输运部110、控温部120和信号检测部130的结构和形状的不同,可采用不同的布置方式,本公开的实施例对此不作限制。
在本公开的一些实施例中,分析装置100还包括一个或多个控制器。该一个或多个控制器可配置为执行以下操作中至少之一:
与输运部110信号连接,以控制输运部110进行移动;
与加热器121信号连接,以控制加热器121加热检测芯片;
与冷却器122信号连接,以控制冷却器122使检测芯片冷却;以及
与光学传感器131信号连接,以对来自检测芯片的光进行分析。
上述控制器例如可通过中央处理器(CPU)、数字信号处理器(DSP)、单片机、现场可编程门阵列(FPGA)、复杂可编程逻辑器件(CPLD)、专用集成电路(ASIC)等实施,本公开的实施例对此不作限制。
应理解,在本公开的一些实施例中,控制器可实现为多个子控制器,该多个子控制器可分别执行上述操作中至少之一。该多个子控制器可分离地设置或集成在一个控制器中,本公开的实施例对此不作限制。
在本公开的一些实施例中,分析装置100还可包括通信部。该通信部配置为与移动终端、服务器等形成信号连接。该信号连接可以是有线连接,也可以是无线连接,本公开的实施例对此不作限制。示例性无线连接包括无线保真(Wi-Fi)、蓝牙、无线直接(Wireless Direct)和红外线。示例性有线连接包括通用串行总线(USB)、火线(FireWire)、雷雳(Thunderbolt)或需要物理电缆的任何连接。
图11A至图11G分别是根据本公开至少一个实施例的分析装置的外壳200的立体图和六面视图(除了顶面之外)。如图11B所示,根据本公开至少一个实施例的分析装置还可包括显示屏201。该显示屏201例如设置在外壳200的正面,且配置为进行显示,例如可以为液晶显示屏、有机发光二极管(OLED)显示屏、量子点发光二极管(QLED)显示屏、微发光二极管显示屏、电子墨水屏、电子纸显示屏等,本公开的实施例对此不作限制。例如,显示屏201可以是触控显示屏,以接收用户的输入。然而,应理解,在一些实施例中,分析装置也可不包括显示屏201,而与单独设置的显示屏连接或将数据例如分析结果以数字文件或物理文件的形式输出,本公开的实施例对此不作限制。
可选的,外壳200的正面还可设置有装载阀门202,其在开启时允许载物台1111从其中伸出,以接纳装载板体21。
如图11C所示,根据本公开至少一个实施例的分析装置还可包括电源接口203。该电源接口203例如设置在外壳200的背面,分析装置通过电源接口203连接至电源以获得电能。然而,应理解,在一些实施例中,分析装置也可不具有电源接口203,而内置有一次电池或二次电池,或内置太阳能电池,本公开的实施例对此不作限制。
如图11C所示,根据本公开至少一个实施例的分析装置还可包括数据传输接口204。数据传输接口204例如设置在外壳200的背面,且配置为将分析装置的数据例如分析结果输出给外部设备,或将来自外部设备的数据传输至分析装置中。数据传输接口204如可以是通用串行总线(USB)接口、串行高级技术附件(SATA)接口等。在至少一个实施例中,数据传输接口和电源接口可以合并为一个接口,例如为USB接口,既可以用于传输数据也可以用于传输电能。根据本公开至少一个实施例的分析装置还可包括按键。按键配置为获取用户的输入指令,例如可以为机械式按键、光学式按键等,本公开的实施例对此不作限制。
如图11D所示,根据本公开至少一个实施例的分析装置还可包括电源开关207和指示灯208,二者例如设置在外壳200的一侧。
如图11E所示,根据本公开至少一个实施例的分析装置还可包括控制阀门209,其例如设置在外壳200的一侧(可与上述电源开关207和指示灯208位于不同侧)。如图11F所示,在取下控制阀门209之后,其内侧设置有磁性贴片211,用以采用磁性吸附的方式固定控制阀门209。当然,在实际应用中,还可以采用其他方式可拆卸地将控制阀门209固定在外壳200上,或者,也可以使控制阀门209与外壳200活动连接,以开启或关闭控制用开口。而且,在取下控制阀门209之后,滤光片转盘212自该控制用开口暴露出来,以能够手动选取荧光通道。并 且,还可以暴露旋钮延长部1361,以进行手动调节焦距。
需要说明的是,荧光通道的选取可以有两种工作模式:一是可以通过上述方式进行人工调节,二是采用内置自动化控制部自动选取荧光通道。类似的,焦距调节也可以有两种工作模式:一是可以采用旋钮延长部1361进行人工调节,二是采用内置自动化控制部自动调节焦距。
如图11G所示,根据本公开至少一个实施例的分析装置还可包括四个支撑地脚213,四个支撑地脚213设置在外壳200的底面上。可选的,四个支撑地脚213具有水平度调节结构(例如包括螺钉和弹性件),以能够对分析装置的整机的水平度进行调节。
如图11C、图11D和图11E所示,根据本公开至少一个实施例的分析装置还可包括散热口205、散热口206和散热口210,三者分别设置在外壳200的背面和两侧,可用于释放控制器或控温部120的热量。这些散热口可采用无尘封装,以避免尘土进入分析装置内部。
根据本公开至少一个实施例的分析装置还可包括触控传感器。触控传感器配置为接收和检测用户的触摸操作,并将用户的触摸操作转换为电信号,以传输至控制器或其他控制设备,例如控制器或外部的服务器等。触控传感器例如可以是电容式触控传感器、电阻式触控传感器等,本公开的实施例对此不作限制。应理解,在显示屏201为触控显示屏或分析装置包括其他形式的输入设备(例如按键、麦克风等)时的情况下,分析装置也可不包括触控传感器。
图12A至图12D示出了根据本公开至少一个实施例的分析装置在装载板体21位于不同位置时的状态图。如图12A所示,根据本公开至少一个实施例分析装置的装载阀门202开启,载物台1111从分析装置的芯片装载口伸出,以接纳装载板体21。如图12B所示,装载板体21 (承载有检测芯片)处于第一位置处,在该第一位置处装载板体21被接纳并承载在载物台1111上。如图12C所示,装载板体21处于第二位置处,此时装载板体21位于测温支架124上的温度传感器123和冷却器122之间,温度传感器123能够检测检测芯片的温度;冷却器122能够对检测芯片降温。该第二位置允许控温部130调节检测芯片的温度。如图12D所示,装载板体21处于第三位置处,此时装载板体21位于物镜134的下方,以使物镜134能够采集来自检测芯片的光。
本公开至少一个实施例还提供了一种分析系统。图13是根据本公开至少一个实施例的分析系统的示意性框图。如图13所示,分析系统300包括分析装置310和检测芯片320,例如,可以将分析装置310以及尚未使用的检测芯片320组合提供给用户,以供用户使用。分析装置310可以是上述的任一分析装置。检测芯片320可以是上述的任一检测芯片。
应理解,本公开的一些实施例中,分析系统300还可以包括更多的组件或部件,本公开的实施例对此不作限制。关于该分析装置310和检测芯片320的详细说明和技术效果可参见上文中关于反应装置的描述,此处不再赘述。
本公开至少一个实施例还提供了一种操作分析装置的方法。该方法适用于根据本公开任一实施例的分析装置。根据本公开至少一个实施例的操作分析装置的方法可包括如下步骤:
步骤1,将承载有装载部(即,芯片装载结构中承载有检测芯片的装载板体)的输运部移动至控温部。
在步骤1中,可手动地将上述输运部移动至控温部。在输运部包括配置为承载装载板体且可至少部分地被驱动的输运结构和配置为能够 驱动输运结构的驱动器的情况下,步骤1可包括通过驱动器驱动承载有装载板体的输运结构,以将装载板体移动至控温部。
图12A至图12D示出了根据本公开至少一个实施例的分析装置在装载板体21位于不同位置时的状态图。如图12A所示,根据本公开至少一个实施例分析装置的装载阀门202开启,载物台1111从分析装置的芯片装载口伸出,以接纳装载板体21。如图12B所示,装载板体21(承载有检测芯片)处于第一位置处,在该第一位置处装载板体21被接纳并承载在载物台1111上。如图12C所示,装载板体21处于第二位置处,此时装载板体21位于测温支架124上的温度传感器123和冷却器122之间,温度传感器123能够检测检测芯片的温度;冷却器122能够对检测芯片降温。该第二位置允许控温部130调节检测芯片的温度。
根据本公开至少一个实施例的操作分析装置的方法还可包括:
步骤2,通过加热器和冷却器调节检测芯片的温度。
在检测芯片具有加热电极并且加热器包括接触电极的情况下,步骤2可包括通过接触电极向检测芯片的加热电极施加电信号,以使加热电极加热检测芯片。
在一些实施例中,步骤2还包括:通过加热器和冷却器循环地将检测芯片维持在至少两个温度。例如,通过加热器加热检测芯片和通过冷却器给检测芯片降温,对检测芯片实施多个控温循环,例如30个控温循环,以使得检测芯片执行PCR热循环扩增。每个控温循环包括:将检测芯片维持在95℃,10秒;将检测芯片维持在50℃,10秒;将检测芯片维持在72℃,10秒。应理解,上述的控温循环仅是示例性的,本公开的实施例对此不作限制。图14是根据本公开至少一个实施例的控温循环的温度变化图。在图14中,横轴表示时间,单位为分钟,纵轴 表示温度,单位为摄氏度。
根据本公开至少一个实施例的操作分析装置的方法还可包括:
步骤3,将上述输运部移动至信号检测部,并通过光学传感器获得来自检测芯片的光。
在步骤3中,可手动地将上述输运部移动至信号检测部。在上述输运部包括配置为承载装载板体且可至少部分地被驱动的输运结构和配置为能够驱动输运结构的驱动器的情况下,步骤3可包括通过驱动器驱动输运部,以将检测芯片移动至信号检测部。
如图12D所示,装载板体21处于第三位置处,此时装载板体21位于物镜134的下方,以使物镜134能够采集来自检测芯片的光。
步骤3还可包括:使用光照射检测芯片,并通过光学传感器接收检测芯片发出的光作为来自检测芯片的光。
在光学传感器包括图像传感器的情况下,步骤3可包括通过图像传感器获得检测芯片的图像。此外,在信号检测部还包括光源和光传输部的情况下,步骤3可包括:通过光源提供光;通过光传输部传输光源提供的光,以照射检测芯片;以及通过光传输部将检测芯片发出的光作为来自检测芯片的光传输至光学传感器(或光学传感器所包括的图像传感器)。
根据本公开至少一个实施例的操作分析装置的方法还可包括:
步骤4,对来自检测芯片的光进行分析,以得到分析结果。
应理解,上述的方法中的一个或多个步骤及至少部分子步骤例如可通过软件或固件执行,例如通过与分析装置信号连接的移动终端、服务器等执行,本公开的实施例对此不作限制。
在一些实施例中,在通过光学传感器获得来自检测芯片的光包括通 过图像传感器获得检测芯片的光学图像的情况下,以光学图像为生物芯片图像为例,步骤4可采用下述生物芯片图像的分析方法,对高通量低信噪比的矩阵型生物芯片荧光图像进行识别,实现腔室位置定位、样本阴阳性判定的自动化分析。
在一些实施例中,生物芯片图像的分析方法包括:
步骤41,获取生物芯片图像并进行预处理以得到预处理图像;
步骤42,对预处理图像进行角度偏转校正以得到偏转校正图像;
步骤43,对偏转校正图像进行增强处理并根据增强处理后的图像对预处理图像中兴趣区域的阴阳性进行识别。
在一些实施例中,上述步骤41包括:
步骤411,获取原始图像、相机内参矩阵和畸变系数;和
步骤412,根据相机内参矩阵和畸变系数对原始图像进行校正以得到生物芯片图像。
可以理解,通过获取相机内参矩阵以及畸变系数可以校正相机采集的原始图像中产生的畸变,从而使得校正后的生物芯片图像可以更真实地显示出生物芯片的特性。如此,可以有利于保证生物芯片分析的有效性和准确性。
在一些例子中,生物芯片可以为四边形,生物芯片上呈阵列排布有多个反应腔室。需要说明的是,在本申请实施方式中以生物芯片图像中反应腔室所在的区域为兴趣区域进行说明。
在某些实施方式中,生物芯片图像的分析方法包括:利用标定板,采用传统标定法标定拍摄用的相机,以获得相机内参矩阵和畸变系数。
其中,通过标定板对相机参数进行标定时,标定板可以具有预定的图案,例如网格图案或黑白方块图案等,相机在一定的拍摄距离下拍摄 标定板的图像,如此,可以将标定板的图像与标定板的图案进行对比,根据标定板图像和标定板的图案中对应特征点的偏移,结合拍摄距离得到相机拍摄相关的相机内参矩阵和畸变参数。
需要说明的是,在一些实施例中,相机内参矩阵和畸变系数可以是预先标定好并预存在相机或生物芯片图像的分析装置中,如此,分析装置可以从相机获取对应的相机内参矩阵和畸变系数,或者根据相机的编号或型号确定相机内参矩阵和畸变系数。当然,在其他实施例中,分析装置还可以是每次获取生物芯片的图像之前,均检测相应相机对应的相机内参矩阵和畸变系数,如此,可以保证相机内参矩阵和畸变系数的有效性。
在某些实施方式中,原始图像为发生了生物化学反应的生物芯片的荧光图像。
其中,当待检测的生物样本被加载到生物芯片上,并发生了生物化学反应后,利用特定的设备,可以采集到对应的生物芯片的荧光图像。可以理解,荧光图像中,通常不同的反应腔室显示的色彩、亮度可以相同或不相同。
在一些实施例中,预处理图像包括高频分量图像,上述步骤41包括:
步骤413,对生物芯片图像进行高斯滤波处理以得到低频分量图像;和
步骤414,利用生物芯片图像减去低频分量图像以得到高频分量图像。
如此,利用高斯滤波得到低频分量图像,然后将生物芯片图像中的低频分量减去得到高频分量图像,从而实现高频滤波,从而解决微观芯 片的荧光光照不均问题。
当然,在其他实施方式中,预处理图像可以不限于上述讨论的高频分量图像,而可以根据实际需求获取灰度图像、低频分量图像和边缘检测图像等。其中灰度图像可以根据图像灰度化处理得到,低频分量图像可以通过低频分量提取处理得到,边缘检测图像可以通过图像边缘提取处理得到。此外,预处理图像还可以上述处理方法中的一种或多种处理方法按预设顺序处理得到,在此不做具体限定。
在一些实施例中,上述步骤42包括:
步骤421,在预处理图像中选择预设数量的检测区域;
步骤422,利用霍夫圆变换检测检测区域内的兴趣区域的中心和半径;和
步骤423,根据兴趣区域的中心和半径做圆以确定兴趣区域并对兴趣区域进行分割。
以兴趣区域为图像中反应腔室所在的区域为例,在检测反应腔室的排列时,需要确定检测区域内的反应腔室的位置,由于反应腔室一般为圆形,如此,通过霍夫变换可以实现腔室中心和半径的检测,进一步地,根据腔室中心和半径确定反应腔室的位置后,可以实现对反应腔室的分割。
在某些实施方式中,上述步骤421包括:在预处理图像的预定区域内选择相应的检测区域。
其中,预设区域可以是用户根据经验进行设定的,或根据算法自动选择的。当然,检测区域还可以是在预处理图像中随机选取的区域,在此不做具体限定
在一些实施例中,检测区域为长方形区域,检测区域中包括至少两 行或至少两列的部分兴趣区域。
可以理解,对高频分量图像进行偏转校正得到偏转校正图像时,需要确定高频分量图像的偏转角度。由于生物芯片上的反应腔室一般呈阵列设置,即兴趣区域一般呈阵列设置,如此,通过腔室的排列方向可实现图像偏转角度的检测,采用长方形区域有利于确定选择的检测区域长边方向与反应腔室排列方向的相对偏转角度。
其中,检测区域中包括至少两行或至少两列的部分兴趣区域可以保证反应腔室排列方向的检测。
需要说明的是,检测区域的尺寸可以根据兴趣区域的区域间距以及兴趣区域的半径等灵活配置,在此不做具体限定。
当然,在其他实施方式中,检测区域的形状可以不限于上述讨论的长方形,而可以根据实际需要选择正方形、三角形、圆形、平行四边形等其他合适的形状,在此不做具体限定。
在某些实施方式中,每次选取的检测区域的预设数量可以是多个,多个检测区域的方向可以不同,从而提高图像偏转角度检测的效率和准确性。例如,每次选取的检测区域的预设数量可以是9个。
在一些实施例中,上述步骤42包括:
步骤424,对分割的图像进行膨胀处理以在预设方向上连通相邻的兴趣区域;
步骤425,取膨胀处理后检测区域内的最大轮廓进行主成分分析以得到轮廓方向;和
步骤426,根据轮廓方向确定图像偏转角度以对预处理图像进行校正得到偏转校正图像。
在步骤424中,可以将分割后的兴趣区域按预设方向进行膨胀处理, 使得兴趣区域的轮廓沿预设方向延伸,从而相邻的兴趣区域的轮廓相互连通。在一个例子中,预设方向可以是长方形的检测区域的长边方向。图15示出了检测区域为9个时,对9个腔室内的兴趣区域按预设方向进行膨胀处理后得到的轮廓示意图。
兴趣区域的轮廓相连通后,步骤425中选择检测区域内的最大轮廓进行PCA主成分分析以得到轮廓方向。可以理解,由于最大轮廓一般为相邻的多个兴趣区域连通形成,在一个例子中,得到的轮廓方向即可以作为反应腔室的排列方向。特别地,有多个检测区域时,可以去多个检测区域中的最大轮廓进行PCA主成分分析以得到轮廓方向。
从而步骤425可以根据轮廓方向确定生物芯片图像和预处理图像的图像偏转角度,以及对生物芯片图像和/或预处理量图像进行偏转角度校正得到偏转校正图像。
如此,本申请可以通过邻接同向兴趣区域形成最大轮廓然后利用PCA主成分分析法解决偏转角度检测的问题。
在一些实施例中,上述步骤42包括:
步骤427,以预设比例增大选择区域重新在预处理图像中随机选择预设数量的检测区域;和
步骤428,重复迭代检测图像偏转角度直至图像偏转角度小于预设角度阈值以得到偏转校正图像。
如此,通过不同大小的检测区域重复迭代检测图像偏转角度,从而保证图像偏转角度的准确性。
在某些实施方式中,预设角度阈值取值范围可以通过下列条件式确定:
Figure PCTCN2021090878-appb-000001
其中,θ为预设角度阈值,dist为兴趣区域的区域间距,rad为兴趣区域的区域半径,m为检测区域内兴趣区域的行数,n为检测区域内兴趣区域的列数。
需要说明的是,在一些实施例中,生物芯片图像可以在拍摄时借助硬件仪器设备进行精确对准,从而可以根据精确对准后拍摄的生物芯片图像直接确定偏转校正图像,此时,可省略检测图像偏转角度的过程。在另一些实施例中,生物芯片实体上还可以设置标志位,获取生物芯片图像后,可以通过识别生物芯片上的标志位来构建相对坐标系,获取芯片相对摄像头偏转角度,进而校正得到偏转校正图像。
当然,角度偏转校正可以不限于上述讨论的实施方式,而可以根据实际情况选择合适的校正方法,使得分析装置可以根据偏转校正图像确定芯片上的兴趣区域满足横向或纵向排列相对位置,在此不做具体限定。
在一些实施例中,上述步骤42包括:
步骤427’,以预设比例增大选择区域重新在预处理图像中随机选择预设数量的检测区域;和
步骤428’,重复迭代检测图像偏转角度预设次数以得到偏转校正图像。
如此,通过不同大小的检测区域重复迭代检测图像偏转角度预设次数,同样可以保证图像偏转角度的准确性。在一个例子中,预设次数可以由系统预设或有用户根据实际情况进行设置,例如,预设次数可以是6次。
在一些实施例中,上述步骤43包括:
步骤431,构建陷波滤波器;和
步骤432,利用陷波滤波器对偏转校正图像进行滤波处理得到周期性图式增强图像。
如此,利用矩阵型生物芯片的周期性图式先验,通过构建陷波滤波器,最大程度减弱了表面污渍、进样过程、反应过程造成的噪声。
在一个例子中,如图16所示的生物芯片图像傅立叶变换到频域得到的幅值图中,大部分图像信息集中于低频部分,因而通过滤除中央部分的图像信息能够去除大部分图像噪声,同时,位于中央竖直和中央水平方向的信息是最易滤出的周期性图式信息,如此,步骤431中构建陷波滤波器可以如图17所示,以用于去除非周期性图式的图像噪声。
采用陷波滤波器可以使得本申请实施方式的生物芯片图像的分析方法的算法的时间、空间复杂度更低,对硬件设备的性能要求更宽松,从而在保证效果的同时降低了成本、提高运行效率。
在一些实施例中,上述步骤433包括:
步骤4331,采用盒式滤波器对周期性图式增强图像进行平滑滤波处理;
步骤4332,对平滑后的图像进行水平方向和竖直方向的像素值积分以获得水平方向的第一积分曲线和竖直方向的第二积分曲线,取第一积分曲线和第二积分曲线的极小值点集以确定网格间隔线;和
步骤4333,根据网格间隔线划分网格区域。
如此,采用盒式滤波器平滑可以有利于减弱图像中存在的其他噪声干扰影像,进而划分网格区域。
在某些实施方式中,盒式滤波器的算子的长宽满足下列条件式:
Figure PCTCN2021090878-appb-000002
其中,b为盒式滤波器的算子的长宽,dist为兴趣区域的区域间距,rad为兴趣区域的区域半径。
在一些实施例中,上述步骤43包括:
步骤434,利用霍夫圆变换检测偏转校正图像中的兴趣区域;和
步骤435,根据检测到的兴趣区域画圆做近似以划分得到网格区域。
也即是说,对于网格区域的划分,还可以采用霍夫原变换的方式检测偏转校正图像中的兴趣区域,然后根据检测到的兴趣区域室画圆做近似以得到网格区域,从而实现网格区域的划分。
当然,对于网格区域的划分,可以不限于上述讨论的实施方式,而可以根据需要采用其他的划分方法进行划分,在此不做具体限定。
在一些实施例中,上述步骤44包括:
步骤441,遍历网格区域,对预处理图像对应的每个网格区域求取像素值均方差;
步骤442,在均方差大于方差阈值时,标记对应的兴趣区域样本为阳性;和
步骤443,在均方差不大于方差阈值时,标记对应的兴趣区域样本为阴性。
如此,根据各个网格的像素值均方差与方差阈值进行比较,从而实现阴阳性的划分。
在某些实施方式中,生物芯片图像的分析方法包括:输出反应腔室的阴阳性识别结果。
本申请实施方式的生物芯片图像的分析方法,能够实现对高通量低 信噪比的矩阵型生物芯片荧光图像的有效识别,具体的,通过高频滤波解决了微观芯片的荧光光照不均问题;通过邻接同向腔室最大轮廓PCA主成分分析法解决了偏转角度检测的问题;利用矩阵型生物芯片的周期性图式先验,通过构建陷波滤波器最大程度减弱了表面污渍、进样过程、反应过程造成的噪声,成功实现腔室位置定位、样本阴阳性判定的自动化分析。
有以下几点需要说明:
(1)本公开实施例附图只涉及到本公开实施例涉及到的结构,其他结构可参考通常设计。
(2)在不冲突的情况下,本公开的实施例及实施例中的特征可以相互组合以得到新的实施例。
以上所述,仅为本公开的具体实施方式,但本公开的保护范围并不局限于此,本公开的保护范围应以所述权利要求的保护范围为准。

Claims (24)

  1. 一种芯片装载结构,其中,包括装载板体,所述装载板体具有用于容纳检测芯片的容置空间;
    所述装载板体的第一板面上设置有贯通至所述容置空间的第一镂空区和至少一个第二镂空区,其中,所述第一镂空区用于暴露所述检测芯片的反应观测区;至少一个所述第二镂空区用于暴露所述检测芯片的至少一个试剂端口;
    所述装载板体上还设置有连接部,所述连接部能够采用可拆卸地方式与分析装置中的用于运送所述装载板体的输运部连接。
  2. 根据权利要求1所述的芯片装载结构,其中,在所述第一板面上,且位于所述第一镂空区所在位置处设置有第一凹陷部,所述第一凹陷部在所述第一板面上的正投影面积大于所述第一镂空区在所述第一板面上的正投影面积,且所述第一凹陷部在所述第一板面上的正投影完全覆盖所述第一镂空区在所述第一板面上的正投影。
  3. 根据权利要求1所述的芯片装载结构,其中,所述第一镂空区在所述第一板面上的正投影形状包括正方形、矩形或者圆形。
  4. 根据权利要求1所述的芯片装载结构,其中,所述第二镂空区为多个,且沿所述第一板面的第一轴线间隔设置,所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
  5. 根据权利要求4所述的芯片装载结构,其中,在所述第一板面上,且位于每个所述第二镂空区所在位置处均设置有第二凹陷部,所述第二凹陷部在所述第一板面上的正投影面积大于所述第二镂空区在所述第一板面上的正投影面积,且所述第二凹陷部在所述第一板面上的正投影完全覆盖所述第二镂空区在所述第一板面上的正投影。
  6. 根据权利要求5所述的芯片装载结构,其中,在所述装载板体置于 所述输运部上时,在所述第一移动方向上靠后的所述第二凹陷部在所述第一板面上的正投影面积大于在所述第一移动方向上靠前的所述第二凹陷部在所述第一板面上的正投影面积;
    在所述第一移动方向上靠后的所述第二凹陷部在所述第一板面上的正投影为长圆形;在所述第一移动方向上靠前的所述第二凹陷部在所述第一板面上的正投影为圆形。
  7. 根据权利要求1所述的芯片装载结构,其中,所述检测芯片还具有加热电极;所述第一板面上设置有贯通至所述容置空间的第三镂空区,用于暴露所述加热电极。
  8. 根据权利要求7所述的芯片装载结构,其中,所述第三镂空区延伸至所述第一板面的第一侧边;
    所述第一侧边与所述第一板面的第一轴线相互垂直;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行,且所述第一侧边为在所述第一移动方向上靠前的侧边。
  9. 根据权利要求1所述的芯片装载结构,其中,在所述装载板体的与所述第一板面相背离的第二板面上设置有容置槽,用以构成所述容置空间,且在所述容置槽的内侧面设置有凸出结构,用以将所述检测芯片限定在所述容置槽中。
  10. 根据权利要求9所述的芯片装载结构,其中,所述凸出结构包括分布在所述第一板面的第一轴线两侧的两组凸部组,每组所述凸部组均包括沿所述第一轴线间隔分布的多个凸部,每个所述凸部自所述容置槽的内侧面朝靠近所述第一轴线的方向凸出,用以与置于所述容置槽中的所述检测芯片的侧面相抵;
    所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
  11. 根据权利要求10所述的芯片装载结构,其中,所述凸部在所述第二板面上的正投影形状包括圆弧形。
  12. 根据权利要求9所述的芯片装载结构,其中,所述容置槽延伸至所述第二板面的第二侧边;
    所述第二侧边与所述第一板面的第一轴线相互垂直;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行,且所述第二侧边为在所述第一移动方向上靠前的侧边。
  13. 根据权利要求1所述的芯片装载结构,其中,在所述装载本体的位于在所述第一板面的第一轴线两侧的两个侧面上分别设置有插槽组,每组所述插槽组均包括一个或沿所述第一轴线间隔设置的多个插槽,所述插槽用作所述连接部一一对应地与所述输运部中的插接件插接;所述第一轴线在所述装载板体置于所述输运部上时的方向,与所述输运部移入所述分析装置内部的第一移动方向相互平行。
  14. 根据权利要求13所述的芯片装载结构,其中,在所述装载板体的与所述第一板面相背离的第二板面上设置有与所述插槽连通的插口,用以供对应的所述插接件移入或移出所述插槽;并且,在所述插槽的位于其第二轴线一侧的侧面上设置有相对于该侧面朝靠近所述第二轴线的方向凸出的限位凸部,用以在所述插接件移动至所述限位凸部和与之相对的所述插槽的底面之间的间隔位置处时,将所述插接件限定在所述插槽中;所述插槽的第二轴线与所述插接件移入或移出所述插槽的移动方向相互平行。
  15. 一种分析装置,包括:装载部、输运部、控温部和信号检测部,其中,
    所述装载部采用权利要求1-14中任意一项所述的芯片装载结构,用于承载检测芯片,且能够与所述输运部可拆卸地连接;
    所述输运部配置为运送所述芯片装载结构;
    所述控温部包括加热器以及冷却器,其中,所述加热器配置为加热所述检测芯片,所述冷却器配置为对所述检测芯片降温;以及
    所述信号检测部包括光学传感器,其中,所述光学传感器配置为接收来自所述检测芯片的光并根据所述光进行检测。
  16. 根据权利要求15所述的分析装置,其中,所述输运部包括:
    输运结构,配置为承载所述芯片装载结构且可至少部分被驱动;以及
    驱动器,配置为能够驱动所述输运结构,以将所述芯片装载结构在第一位置、第二位置和第三位置之间往复移动,
    其中,所述第一位置允许将所述芯片装载结构接纳在所述输运结构中;
    所述第二位置允许所述控温部调节所述检测芯片的温度;以及
    所述第三位置允许所述信号检测部的所述光学传感器接收来自所述检测芯片的所述光。
  17. 根据权利要求16所述的分析装置,其中,所述输运结构包括:
    载物台,配置为在使用中承载所述芯片装载结构;
    可移动平台,配置为与所述驱动器连接,以在所述驱动器的驱动下进行移动;以及
    支架,配置为连接所述载物台和所述可移动平台,由此使得当可移动平台被驱动时可以带动载物台。
  18. 根据权利要求17所述的分析装置,其中,所述装载部采用权利要求13或14所述的芯片装载结构;
    在所述载物台的承载面上设置有用于容纳所述装载板体的安装槽,且在所述载物台的第一侧面设置有与所述安装槽连通的安装槽开口,用以供所述装载板体移入或移出所述安装槽,所述第一侧面与所述载物台移入所述分析装置内部的第一移动方向相互垂直,且为在所述第一移动方向上朝后的侧面;
    并且,在所述载物台上还设置有自所述安装槽的侧面朝靠近所述安装槽 的第三轴线的方向凸出的所述插接件;所述第三轴线与所述第一移动方向相互平行。
  19. 根据权利要求17所述的分析装置,其中,所述装载部采用权利要求7所述的芯片装载结构;
    所述加热器包括至少一个接触电极,至少一个所述接触电极配置为在使用中一一对应地与所述检测芯片的至少一个所述加热电极电接触;
    所述加热器还配置为通过所述接触电极向所述检测芯片的所述加热电极施加电信号,以使所述加热电极加热所述检测芯片。
  20. 根据权利要求19所述的分析装置,其中,所述接触电极固定在所述载物台的承载面上,且位于所述安装槽的与所述安装槽开口相对的一侧,并且所述接触电极的一端相对于所述安装槽的侧面沿与所述载物台移入所述分析装置内的第一移动方向相反的方向凸出;
    所述接触电极设置有用于与所述加热电极电接触的接触部,所述接触部相对于所述接触电极的与所述加热电极相对的表面,朝靠近所述加热电极的方向凸出;并且,所述加热器还包括弹性件,所述弹性件分别与所述接触电极和所述载物台连接,用以向所述接触电极施加朝向所述载物台的承载面的拉力。
  21. 根据权利要求20所述的分析装置,其中,所述弹性件包括弹簧。
  22. 根据权利要求19所述的分析装置,其中,在所述载物台的承载面上设置有电极插槽,所述接触电极插设在所述电极插槽中,并且所述接触电极与所述载物台通过紧固件固定连接。
  23. 根据权利要求15所述的分析装置,其中,所述信号检测部还包括:
    光源,配置为在使用中提供光以照射所述检测芯片;
    光传输部,配置为在使用中将所述光源提供的所述光传输至所述检测芯片以及将由所述检测芯片发出的光传输至所述光学传感器;以及
    托架,用于固定和承载所述光源和所述光传输部,且在所述托架上还设 置有焦距调节结构,所述焦距调节结构配置为调节所述光传输部与所述检测芯片之间的距离,以使所述检测芯片位于所述光传输部的焦点处;并且,所述焦距调节结构具有焦距调节旋钮以及与所述焦距调节旋钮连接的旋钮延长部,所述旋钮延长部延伸至靠近所述光传输部的一侧,以便于人工调节。
  24. 一种分析系统,包括:
    如权利要求15至23中任一项所述的分析装置;以及
    所述检测芯片。
PCT/CN2021/090878 2021-04-29 2021-04-29 芯片装载结构、分析装置及分析系统 WO2022226868A1 (zh)

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