CN108624493B - Integrated DNA Analyzer - Google Patents

Integrated DNA Analyzer Download PDF

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Publication number
CN108624493B
CN108624493B CN201810866116.1A CN201810866116A CN108624493B CN 108624493 B CN108624493 B CN 108624493B CN 201810866116 A CN201810866116 A CN 201810866116A CN 108624493 B CN108624493 B CN 108624493B
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capillary
assembly
pcr reaction
component
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CN108624493A (en
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曹健荣
王承
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Denogen Beijing Bio Sci&tech Co ltd
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Denogen Beijing Bio Sci&tech Co ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/686Polymerase chain reaction [PCR]

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  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention discloses an integrated DNA analyzer, which comprises a sample processing system and a capillary electrophoresis system; the sample processing system comprises a sample extraction area, a PCR reaction area and a liquid shifter, wherein the liquid shifter can move between the sample extraction area and the PCR reaction area to finish DNA extraction of a sample and PCR reaction after extraction, and an electrophoresis component is arranged in the PCR reaction area; the capillary electrophoresis system comprises a capillary component, the anode end of the capillary component is connected with a glue filling component, an optical detection component is arranged at a detection window, a motion platform component is arranged at the cathode end of the capillary component, and the motion platform component can connect the electrophoresis component in the PCR reaction zone with the cathode end of the capillary component. According to the invention, all steps of DNA detection and analysis are integrated on one miniaturized device, so that the operation is convenient, the detection is rapid, the efficiency of DNA detection is greatly improved on the premise of ensuring the accuracy, and meanwhile, the portability of movement is greatly improved by the integrated miniaturized device, and the range of applicable places is enlarged.

Description

Integrated DNA analyzer
Technical Field
The invention relates to the field of DNA analysis and detection, in particular to an integrated DNA analyzer.
Background
The DNA analysis technology has wide application fields. In the basic research field, DNA analysis is mainly applied to genome sequencing, gene expression profile analysis, gene mutation, polymorphism analysis and the like; in the clinical medicine field, the diagnosis of clinical diseases and drug research and development can be performed; in the judicial identification field, individual identification and parent identification can be performed; in the agricultural field, animal and plant crossbreeding research and transgenic food safety detection can be performed.
Taking the forensic field as an example, along with the development of technology, the forensic DNA detection technology has become an indispensable scientific tool for individual identification and crime attack in public security. For decades, forensic DNA detection techniques have undergone three technological innovations in multi-site DNA fingerprinting analysis techniques, amplified fragment length polymorphism analysis techniques, and mitochondrial DNA detection techniques. Currently, a technology system mainly comprising a fluorescence labeling multi-locus STR multiplex amplification detection technology, a mitochondrial DNA detection technology and a SNP analysis technology is developed.
The realization of the technologies is not separated from a corresponding detection platform, and the development of forensic DNA detection instruments determines the practical performance and development speed of various forensic DNA detection technologies. Therefore, such instruments are becoming a research hotspot in the forensic science field and the analytical instrument field. However, the existing equipment has defects of different degrees, such as higher requirements on the professional of operation, inapplicability to non-professional personnel, and difficulty in large-scale application and popularization in conventional forensic DNA detection equipment in a short period.
Disclosure of Invention
The invention aims to provide an integrated DNA analyzer with functions of integration, operation simplification, using dexterity, detection rapidness and mobile portability.
In order to achieve the above object, the specific technical scheme of the integrated DNA analyzer of the present invention is as follows:
an integrated DNA analyzer comprises an analyzer shell, wherein a sample processing system and a capillary electrophoresis system are arranged in the analyzer shell; the sample processing system comprises a sample extraction area, a PCR reaction area and a liquid shifter, wherein the liquid shifter can move between the sample extraction area and the PCR reaction area so as to finish DNA extraction of a sample in the sample extraction area and finish PCR reaction of the extracted DNA in the PCR reaction area, and an electrophoresis component is arranged in the PCR reaction area; the capillary electrophoresis system comprises a capillary component, wherein a motion platform component is arranged at the cathode end of the capillary component, the motion platform component can connect the electrophoresis component in the PCR reaction zone with the cathode end of the capillary component, the anode end of the capillary component is connected with a glue filling component, and an optical detection component is arranged at a detection window of the capillary component.
The integrated DNA analyzer of the invention has the following advantages:
1) All steps of DNA detection and analysis are integrated on one miniaturized device, so that the operation is convenient, the detection is quick, the efficiency of DNA detection is greatly improved on the premise of ensuring the accuracy, and meanwhile, the portability of movement is greatly improved by the integrated miniaturized device, and the range of applicable places is enlarged.
2) From sample to result, the user does not need to operate in a standard PCR laboratory, and the DNA extraction process, the PCR product mixing and capillary electrophoresis process, the signal detection process and the like can be automatically carried out, and the kit also has the short-term reagent preservation function and can be widely applied to the fields of public security, judicial and clinic.
Drawings
FIG. 1 is a front view of an integrated DNA analyzer of the present invention;
FIG. 2 is a rear view of the integrated DNA analyzer of the present invention;
FIG. 3 is a schematic diagram of the sample processing system of FIG. 1;
FIG. 4 is a top view of the processing device of FIG. 3;
FIG. 5 is a perspective view of the PCR reaction area of FIG. 4;
FIG. 6 is a split view of the PCR reaction assembly of FIG. 5;
FIG. 7 is an assembled perspective view of the metal reaction tank and the temperature control unit of FIG. 6;
FIG. 8 is a perspective view of the displacement assembly of FIG. 5;
FIG. 9 is a perspective view of the pipetting device of FIG. 3;
FIG. 10 is an enlarged view of a portion of the pipetting device of FIG. 9;
FIG. 11 is a perspective view of the pipette of FIG. 9;
FIG. 12 is a perspective view of another embodiment of the pipette of FIG. 9;
FIG. 13 is a perspective view of the magnetic pipette of FIG. 9;
FIG. 14 is a partially exploded view of the magnetic pipette of FIG. 13;
FIG. 15 is a perspective view of the magnetic assembly of FIG. 13;
FIG. 16 is a first operational state diagram of the magnetic pipette of FIG. 13;
FIG. 17 is a second operational state diagram of the magnetic pipette of FIG. 13;
FIG. 18 is a schematic diagram of the capillary electrophoresis system of FIG. 1;
FIG. 19 is a disassembled view of the capillary tube assembly of FIG. 18;
FIG. 20 is a perspective view of the motion platform assembly of FIG. 18;
FIG. 21 is a perspective view of the glue dispensing assembly of FIG. 18;
FIG. 22 is a perspective view of another embodiment of the glue dispensing assembly of FIG. 18;
FIG. 23 is a split view of the glue dispensing assembly of FIG. 22;
FIG. 24 is a front view of yet another embodiment of the glue dispensing assembly of FIG. 18;
FIG. 25 is a rear view of the glue dispensing assembly of FIG. 24;
FIG. 26 is a front view of the body portion of the glue dispensing assembly of FIG. 24;
FIG. 27 is a rear view of the body portion of the glue dispensing assembly of FIG. 24;
FIG. 28 is a perspective view of the support element of FIG. 26;
FIG. 29 is a perspective view of the storage element of FIG. 26;
FIG. 30 is a front view of the glue block element of FIG. 26;
FIG. 31 is a rear view of the glue block element of FIG. 26;
FIG. 32 is a longitudinal cross-sectional view of the slab element of FIG. 26;
FIG. 33 is a transverse cross-sectional view of the glue block element of FIG. 26;
FIG. 34 is a front view of the optical detection assembly of FIG. 18;
FIG. 35 is a rear view of the optical detection assembly of FIG. 18;
fig. 36 is an optical path diagram of the optical detection assembly of fig. 18.
Detailed Description
For a better understanding of the objects, structures and functions of the present invention, an integrated DNA analyzer according to the present invention will be described in further detail with reference to the accompanying drawings.
Compared with the traditional DNA analysis equipment, the integrated DNA analyzer integrates almost all steps in the DNA analysis process such as sample extraction, PCR reaction, electrophoresis separation, fluorescence detection and the like, so that the DNA analysis process can be completed in one whole equipment, the use scene of the equipment is greatly improved, and the integrated DNA analyzer can be widely applied to the fields of public security, judicial, clinic and the like.
As shown in fig. 1 and 2, the integrated DNA analyzer of the present invention includes a sample processing system 1 and a capillary electrophoresis system 2 according to the functional area division, and the sample processing system 1 and the capillary electrophoresis system 2 are disposed inside an analyzer housing (not shown in the drawings) to constitute a miniaturized DNA analyzer. The sample processing system 1 is used for carrying out DNA extraction and PCR reaction after the extraction on a sample; the capillary electrophoresis system 2 is used to perform capillary electrophoresis and detection analysis of reactants. In addition, it should be noted that the integrated DNA analyzer of the present invention is also provided with auxiliary structures such as a control system and a power supply system, so as to achieve automation of the operation of the apparatus.
Sample processing system 1
As shown in fig. 3 to 17, which are a preferred example of the sample processing system in the present invention. In this embodiment, the sample processing system 1 includes a processing device 100 and a pipetting device 200, where the processing device 100 includes a mounting plate 110, and a sample extraction area 120 and a PCR reaction area 130 are disposed on the mounting plate 110, where the sample extraction area 120 can extract DNA from a sample, and the PCR reaction area 130 can perform PCR reaction on the extracted DNA; the pipetting device 200 comprises a supporting frame 210, a moving device 220 and a pipetting device 230, wherein the supporting frame 210 is arranged above the processing device 100, the moving device 220 is arranged on the supporting frame 210, and the pipetting device 230 can be driven by the moving device 220 to move on the supporting frame 210 so as to realize sample extraction and transfer of samples, reagents and other substances in the processing device in the PCR reaction process. Therefore, the sample processing system can realize the integrated operation of sample processing through the cooperation of the processing device and the pipetting device.
Further, as shown in fig. 4 to 8, it is a preferable example of the processing apparatus in the present invention. In this embodiment, the processing apparatus 100 includes a mounting base plate 110, where the mounting base plate 110 is an integral component, a partition 150 is disposed on the mounting base plate 110, one side of the partition 150 is a sample extraction area 120, and the other side is a PCR reaction area 130, so that by disposing the partition 150 in the middle, the sample extraction area 120 and the PCR reaction area 130 are relatively independent, and occurrence of mutual pollution is reduced.
Further, the sample extraction region 120 is used to extract DNA from a sample, and includes a reagent storage assembly 121, a sample extraction assembly 122, a gun head storage assembly 123, and a waste storage assembly 124. The reagent storage component 121 can store various reagents at normal temperature, such as magnetic beads, lysate, binding solution, washing solution, rinsing solution, eluent, isopropanol, absolute ethanol, proteinase K, etc., and it should be noted that the number and types of the reagents contained in the reagent storage component may be different according to different requirements.
Further, the sample extraction assembly 122 includes one or more reaction wells to meet different flux requirements, and a temperature control module is disposed below the reaction wells, which can heat or cool the extraction reaction. The DNA extraction in the sample extraction assembly can be achieved by the following method: 1) The DNA is extracted by a magnetic bead method in cooperation with a magnetic pipette to be described later; 2) Is used in combination with a conventional pipette to be described later, and is provided with a magnetic device such as a movable magnetic rod, etc., and DNA is extracted by a magnetic bead method. It should be noted that the specific extraction method in the present invention is not limited to a great extent, as long as the extraction of DNA can be conveniently accomplished by using the apparatus of the present invention, and the above method is merely a preferred example.
Further, the gun head storage assembly 123 is used for placing gun heads of various specifications which may be used in the sample extraction process; the waste storage assembly 124 is used to store the used gun tips. When the sample is extracted, the target gun head can be directly taken from the gun head storage assembly by the liquid dispenser, and the gun head can be directly discarded into the waste storage assembly after liquid removal is finished, so that the operation is convenient, the control time is saved, and the automation degree of the sample processing system is improved.
It should be noted that, according to practical needs, the sample extracting component 122 in the sample extracting region 120 and the reagent storage component 121 may be combined, that is, the reaction reagent may be directly stored in the reaction well, and when the extracting reaction is performed, the sample may be directly added into the reaction well containing the reagent, so that the process of adding the reagent from the reagent storage component to the sample extracting component is omitted.
Further, as shown in fig. 4 and 5, the PCR reaction region 130 is used to perform a PCR reaction on the extracted DNA, and includes a PCR reaction assembly 131, a low temperature reagent storage assembly 132, a gun head storage assembly 133, and a waste storage assembly 134. The gun head storage assembly 133 and the waste storage assembly 134 are similar to the structure and functions of the sample extraction area 120 described above, and will not be described again.
Further, the PCR reaction assembly 131 includes a reaction tank unit and a temperature control unit, where the reaction tank unit is a carrying container for PCR reaction, and the temperature control unit is connected to the reaction tank unit and is used for controlling the PCR reaction temperature in the reaction tank unit. Specifically, as shown in fig. 6, the reaction tank unit includes a metal reaction tank 136 and a temperature control reaction cover 137 movably disposed above the metal reaction tank 136, wherein the metal reaction tank 136 is preferably made of metal with good thermal conductivity such as gold, silver, aluminum, etc., a plurality of reaction tube insertion holes are formed on the metal reaction tank 136, and PCR reaction tubes can be inserted into the reaction tube insertion holes to complete PCR reaction.
Further, as shown in fig. 6, the temperature-controlled reaction cover 137 is disposed above the metal reaction tank 136, wherein a motor and a rotating shaft are disposed on one side of the metal reaction tank 136, the motor can drive the rotating shaft to rotate, the temperature-controlled reaction cover 137 is connected with the rotating shaft, and the temperature-controlled reaction cover 137 can be opened and closed relative to the metal reaction tank 136 under the driving of the motor, so as to seal a PCR reaction tube inserted into the metal reaction tank 136 when the PCR reaction is performed, thereby ensuring the smooth performance of the PCR reaction. In addition, a heating component is further disposed in the temperature-controlled reaction cover 137, and during the PCR reaction, the metal reaction tank 136 is acted by the temperature-controlled unit to heat the reaction liquid in the PCR reaction tube, so as to avoid volatilizing the reaction liquid into the temperature-controlled reaction cover 137, and the heating component in the temperature-controlled reaction cover 137 can be started at the same time to ensure the normal operation of the PCR reaction.
Further, as shown in fig. 6 and 7, the temperature control unit includes TEC (Thermo Electric Cooler) a temperature control component 138, the metal reaction tank 136 is disposed above the TEC temperature control component 138, and the TEC temperature control component 138 can adjust the temperature of the metal reaction tank 136 to meet the temperature requirement of the PCR reaction. Preferably, since the cooling rate of the TEC temperature control assembly 138 cannot meet the cooling requirement of the PCR reaction, a radiator 139 is further disposed below the TEC temperature control assembly 138, wherein a heat transfer groove is formed at the bottom of the radiator 139, one end of a heat transfer sheet 140 is disposed in the heat transfer groove, and the other end is connected with a cooling fan 141. Therefore, when the metal reaction tank 136 needs to be cooled, the cooling fan 141 is started, and the cooling air flow blown out by the cooling fan 141 passes through the heat transfer sheet 140, so that the TEC temperature control assembly 138 is cooled in an auxiliary manner through the heat transfer sheet 140 and the radiator 139, and the cooling requirement of the PCR reaction is met. In addition, the cooling fan 141 may also direct the aerosol that may be generated in the device to be discharged, for example, to an aerosol treatment device outside the device, etc., so as to provide a good reaction environment.
Further, the low temperature reagent storage component 132 is used to store reagents required for a PCR reaction or a subsequent capillary electrophoresis reaction, such as PCR enzyme solution, PCR primers, PCR templates, PCR buffers, dNTPs, formamide, etc. The low-temperature reagent storage component 132 in this embodiment may have a similar structure to the PCR reaction component 131, i.e. may also include a storage tank unit and a temperature control unit, wherein the difference is that the temperature control reaction cover 137 of the reaction tank unit in the PCR reaction component 131 has a heating function, while the sealing heat preservation cover of the storage tank unit in the low-temperature reagent storage component 132 only has a heat preservation function, because the low-temperature reagent storage component 132 only needs to preserve the PCR reaction reagent or the capillary electrophoresis reaction reagent at a low temperature, and does not need to perform treatments such as heating.
Further, an electrophoresis assembly 135 is also provided in the PCR reaction zone 130 for use with a subsequent capillary electrophoresis system. The electrophoresis assembly 135 is disposed on the mounting base plate 110, and is mainly used for storing substances such as cathode buffer solution, water, sample and the like used in the capillary electrophoresis process, for example, the electrophoresis assembly can comprise a sample tube, a cleaning tube and a buffer tube, and the sample tube can be added with a sample as an analyte of the capillary electrophoresis; pure water can be added into the cleaning pipe for cleaning the capillary; buffer solution can be added into the buffer solution tube for electrophoresis reaction. It should be noted that the arrangement of the positions of the components on the mounting base plate in the reaction apparatus of the present invention is not fixed, and is merely a preferred example in the drawings, and the positions of the components such as the PCR reaction components and the reagent storage components can be flexibly adjusted according to different requirements.
Further, in order to conveniently perform sample extraction and PCR reaction, the reaction device of the present invention may be provided to be movable in the Y-axis direction to match the movement of the pipette in the X-axis direction in the pipetting device. As shown in fig. 8, the mounting base plate 110 of the reaction device may be disposed on a displacement assembly, the displacement assembly includes a Y-axis motor 161, a Y-axis slide rail 162, a Y-axis slide block 163, and a Y-axis bracket 164, the Y-axis slide rail 162 is fixedly disposed on a base or other form of base, the Y-axis slide block 163 is slidably disposed on the Y-axis slide rail 162, the Y-axis slide block 163 is fixedly connected with a motor shaft of the Y-axis motor 161, the motor shaft may drive the Y-axis slide block 163 to reciprocate along the Y-axis slide rail 162, the Y-axis bracket 164 is fixedly disposed on the Y-axis slide block 163, and the mounting base plate 110 of the reaction device is fixedly disposed on the Y-axis bracket 164. Thus, when the reaction device is required to be driven to move in the Y-axis direction, the motor shaft of the Y-axis motor 161 drives the Y-axis slider 163 to move along the Y-axis sliding rail 162, and the Y-axis slider 163 drives the mounting base plate 110 and the above components to move through the Y-axis bracket 164.
In addition, according to practical needs, the reaction device of the present invention may be configured to be movable in both the Y-axis and Z-axis directions to realize three-dimensional movement in cooperation with the movement of the pipette 230 in the X-axis direction in the pipetting device 200, and the movement structure in the Z-axis direction may be designed or adopted by referring to the movement structure in the Y-axis direction described above, and the present invention will not be described in detail.
Further, as shown in fig. 9 to 17, it is a preferable example of the pipetting device in the invention. In this embodiment, the pipetting device 200 includes a support frame 210, a movement device 220, and a pipettor 230. The supporting frame 210 is a portal frame structure, and includes two supporting columns vertically arranged, and a cross beam transversely arranged between the two supporting columns. It should be noted that the specific shape and size of the supporting frame 210 may be flexibly designed according to different arrangements of the mounting base plate 110, and is not limited to the one shown in the drawings.
Further, as shown in fig. 10, the moving device 220 includes a moving motor 221, a connecting piece 222, a sliding block 223 and a sliding rail 224, wherein the moving motor 221 is fixedly arranged on the supporting frame 210, in this embodiment, the moving motor 221 is specifically arranged at a connection position of a supporting column and a cross beam in the supporting frame 210, and a length extending direction of a motor shaft is parallel to a length extending direction of the cross beam; the connecting piece 222 is fixedly connected with the motor shaft and can reciprocate under the drive of the motor shaft; one side of the slider 223 is fixedly arranged on the connecting piece 222, the other side is in sliding connection with the sliding rail 224, the sliding rail 224 is fixedly arranged on a cross beam in the supporting frame 210, and the pipettor 230 is fixedly arranged on the slider 223. Therefore, when the pipettor 230 needs to be moved, the moving motor 221 is started, the connecting piece 222 is driven to move by the motor shaft, and the connecting piece 222 drives the sliding block 223 to move along the sliding rail 224 while moving, so that the pipettor 230 on the sliding block 223 is moved.
Further, in order to improve the pipetting efficiency, two pipettes 230 are provided in the present embodiment, as shown in fig. 9, corresponding to the two pipettes 230, two moving devices 220 are provided on the support frame 210, and the two moving devices 220 are respectively provided at two ends of the support frame 210, that is, at the connection positions of the two support columns and the cross beam. The two pipettes 230 are respectively disposed on the two moving devices 220, and one or both of the pipettes 230 can be selectively controlled according to actual needs, so as to efficiently complete pipetting.
Further, in order to control the movement range of the pipette 230 during the movement process, as shown in fig. 10, a limit switch 240 may be further provided, where, as the first limit component in the limit switch 240 is disposed at the position of the movement motor 221, and the second limit component is disposed on the connecting piece 222, when the motor shaft drives the connecting piece 222 to move toward the direction approaching the movement motor 221, the first limit component and the second limit component are also gradually approaching, and contact with each other when the pipette 230 reaches the limit position, so as to control the displacement stroke of the pipette 230, and avoid damage to the pipette 230 during the movement process.
Further, as shown in fig. 11, it is a preferable example of the pipette in the present invention. In this embodiment, the pipette 300 includes a base plate 310, and an injection motor 320, an injector 330, and a gun head assembly disposed on the base plate 310. The bottom plate 310 is a plate-shaped structure, and is a basic component of the pipette 300, each component of the pipette 300 is disposed on the bottom plate 310, the bottom plate 310 is fixedly disposed on a moving device of the pipetting device, and further the moving device realizes the reciprocating movement of the pipette.
Further, the injector 330 and the injection motor 320 are fixedly disposed on the bottom plate 310, respectively, the push rod of the injector 330 is connected with the motor shaft, the gun head is connected with the injector 330, preferably, the injector 330 comprises an injector body, one end of the injector body is provided with a first connecting piece, the first connecting piece is connected with the motor shaft of the injection motor 320, the other end of the injector body is provided with a second connecting piece, and the second connecting piece is connected with the gun head 350. Thus, when the target liquid needs to be sucked, the injection motor 320 is started, and the motor shaft drives the push rod of the injector 330 to move upwards, so as to provide suction force for the gun head 350 to suck the target liquid; when the target liquid in the gun head 350 needs to be discharged, the injection motor 320 is started, and the motor shaft drives the push rod of the injector 330 to move downwards so as to apply a thrust force to the target liquid in the gun head 350 and push the target liquid out of the gun head 350.
Further, the gun head unloading assembly comprises a supporting rod 341, a first baffle 342 and a second baffle 343 are fixedly arranged on the bottom plate 310, the supporting rod 341 is arranged between the first baffle 342 and the second baffle 343, one end of the supporting rod 341 is fixedly connected with the first baffle 342, the other end of the supporting rod is fixedly connected with the second baffle 343, the length extending direction of the supporting rod 341 is parallel to the length extending direction of the injector 330, the first baffle 342 is arranged close to the injection motor 320, the second baffle 343 is arranged close to the gun head 350, and preferably, the two supporting rods 341 are respectively arranged at two sides of the injector 330 so as to ensure the running stability of equipment.
Further, a gun head pressing frame is sleeved on one side, close to the second baffle 343, of the supporting rod 341, and the gun head pressing frame is of a frame structure and comprises a first pressing plate 344 and a second pressing plate 345, and a connecting rod 346 is arranged between the first pressing plate 344 and the second pressing plate 345. The first pressing plate 344 is sleeved on the supporting rod 341, and is located between the first baffle 342 and the second baffle 343, the connecting rod 346 passes through the second baffle 343, and the second pressing plate 345 is located between the second baffle 343 and the gun head 350, that is, the gun head pressing frame is movably disposed relative to the supporting rod 341 and can move up and down along the supporting rod 341.
Further, a transmission pressing plate 347 is arranged on a motor shaft, the transmission pressing plate 347 is connected with a push rod of the injector 330, and the motor shaft can drive the push rod of the injector 330 to move up and down through the transmission pressing plate 347. Wherein, the transmission pressing plate 347 is sleeved on the supporting rod 341 and can reciprocate relative to the supporting rod 341, the supporting rod 341 is further sleeved with a transmission sleeve 348, the transmission sleeve 348 is positioned between the transmission pressing plate 347 and the first pressing plate 344 on the gun head pressing frame, when the transmission pressing plate 347 descends along the supporting rod 341, the transmission sleeve 348 can be pushed to descend along the supporting rod 341 so as to push the first pressing plate 344 to descend along the supporting rod 341, and then the gun head pressing frame is wholly descended, so that the gun head 350 is detached from the injector 330.
Further, a limit switch 360 may be further disposed on the bottom plate 310, where, as shown in fig. 11, a first limit component in the limit switch 360 is disposed at a position on the bottom plate 310 corresponding to a limit position where the gun head 350 can be detached, and a second limit component is disposed on the transmission pressing plate 347, when the motor shaft drives the transmission pressing plate 347 to descend along the supporting rod 341, the first limit component and the second limit component are gradually close to each other and contact each other when reaching the limit position where the gun head 350 can be detached, so as to control a displacement stroke of the transmission pressing plate 347, and avoid damage to each component of the pipette 300 in the moving process.
Further, a return spring 349 is disposed between the first pressing plate 344 and the second baffle 343, preferably, the return spring 349 is sleeved on the connecting rod 346 between the first pressing plate 344 and the second pressing plate 345, one end of the return spring 349 is in contact with the first pressing plate 344, the other end is in contact with the second baffle 343, and the return spring 349 is supported between the first pressing plate 344 and the second baffle 343 to maintain the relative positional relationship between the gun head pressing frame and the supporting rod 341 as well as the second baffle 343. Thus, when the transmission pressing plate 347 pushes the transmission sleeve 348 to move down along the supporting rod 341, the transmission sleeve 348 pushes the first pressing plate 344 to move towards the direction close to the second baffle 343, that is, the gun head pressing frame integrally moves down, and at this time, the reset spring 349 is compressed; when the transmission pressing plate 347 moves up along the supporting rod 341 and is separated from the transmission sleeve 348, the return spring 349 returns to the original state, and at this time, the return spring 349 pushes the first pressing plate 344 to move away from the second baffle 343, that is, the gun head pressing frame moves up entirely.
The specific working principle of the pipette of the embodiment is as follows: 1) Installing a gun head, moving the liquid shifter to a gun head storage assembly under the drive of a moving device, selecting a target gun head and finishing installation; 2) Sucking target liquid (reagent or sample, etc.), starting an injection motor, and driving a push rod of the injector to move upwards by a motor shaft through a transmission pressing plate, so that the target liquid can be sucked into a gun head connected with the injector; 3) Pushing out target liquid, starting an injection motor, and driving a push rod of the injector to descend by a motor shaft through a transmission pressing plate, wherein the target liquid can be pushed out from a gun head; 4) The gun head is dismounted, the liquid shifter moves to the position of the waste storage component under the drive of the moving device, the motor shaft continuously pushes the transmission pressing plate to move downwards along the supporting rod, the transmission pressing plate is contacted with the transmission sleeve and pushes the transmission sleeve to move downwards along the supporting rod, the transmission sleeve pushes the gun head pressing frame to move downwards along the supporting rod, the reset spring between the first pressing plate and the second baffle in the gun head pressing frame is compressed, the second pressing plate in the gun head pressing frame is contacted with the gun head 4, the gun head is finally separated from the injector, and the gun head falls into the waste storage component; 5) The device resets, and the motor shaft drives the transmission clamp plate and goes up along the bracing piece, and transmission clamp plate and transmission sleeve pipe separation, the reset spring between first clamp plate and the second baffle resumes the original form to promote rifle head press frame and go up along the bracing piece.
Further, as shown in fig. 12, it is another preferable example of the pipette of the present invention. In this embodiment, the pipette 400 includes a housing case 410, a first motor 420, a syringe 430, and a gun head assembly. Wherein the syringe 430 is disposed inside the accommodating case 410; the first motor 420 is disposed at the outside of the accommodating case 410, and the motor shaft is extended into the accommodating case 410 and connected with the push rod of the syringe body to control the upward and downward movement of the push rod of the syringe 430; the gun head 450 is positioned outside the receiving housing 410 and may be connected to the syringe 430 by a gun head connector.
Further, the gun head unloading assembly comprises a second motor 441 and a gun head pressing plate 442, the second motor 441 is arranged inside the accommodating shell 410, the gun head pressing plate 442 is arranged outside the accommodating shell 410, a motor shaft extends out of the accommodating shell 410 and is connected with the gun head pressing plate 442, the gun head pressing plate 442 is positioned between the gun head 450 and the gun head connector, and the motor shaft can push the gun head pressing plate 442 to move towards the direction close to the gun head 450 and finally separate the gun head 450 from the injector 430.
The specific working principle of the pipette of the embodiment is as follows: 1) Installing a gun head, moving the liquid shifter to a gun head storage assembly under the drive of a moving device, selecting a target gun head and finishing installation; 2) Sucking target liquid, starting a first motor, and driving a push rod of the injector to move upwards by a motor shaft, wherein the target liquid can be sucked into a gun head connected with the injector; 3) Pushing out target liquid, starting the first motor, and driving the push rod of the injector to descend by the motor shaft, wherein the target liquid can be pushed out from the gun head; 4) The gun head is dismounted, the liquid shifter moves to the waste storage component under the drive of the moving device, the second motor is started, the motor shaft pushes the gun head pressing plate to move towards the direction close to the gun head, the gun head pressing plate is in contact with the gun head, the gun head is finally separated from the injector, and the gun head falls into the waste storage component; 5) The device resets, starts the second motor, and the motor shaft drives the rifle head clamp plate to move towards the direction of keeping away from the rifle head.
Further, as shown in fig. 13 to 17, it is a preferable example of the magnetic pipette in the present invention. In this embodiment, the magnetic pipette 500 is additionally provided with a magnetic component 520 on the basis of the above-mentioned common pipette, specifically, the magnetic component 520 is disposed on the accommodating housing 510 of the pipette at a position corresponding to the gun head 550, and includes a magnetic motor 521, a connecting rod 522 and a magnet 523, and the magnetic component 520 can be used in cooperation with the gun head 550 on the pipette to complete the DNA extraction operation.
Further, a fixing member 524 is provided on the housing case 510 of the pipette, a motor mounting hole and a motor shaft accommodating hole are provided on the fixing member 524, a motor connecting hole is provided on the magnetic motor 521, and the motor mounting hole on the fixing member 524 and the motor connecting hole on the magnetic motor 521 are connected by a screw, so that the magnetic motor 521 is fixedly provided on the fixing member 524, and a motor shaft is provided through the motor shaft accommodating hole on the fixing member 524 and can rotate in the motor shaft accommodating hole.
Further, one end of the connecting rod 522 is provided with a motor shaft connecting hole, the other end is provided with a magnet accommodating groove, the motor shaft passes through the motor shaft accommodating hole on the fixing piece 524 and is fixedly connected with the motor shaft connecting hole on the connecting rod 522, the motor shaft can drive the connecting rod 522 to rotate, and the magnet 523 is fixedly arranged in the magnet accommodating groove and can rotate along with the connecting rod 522 so as to be close to or far away from the gun head 550 on the pipette 400.
Thus, as shown in fig. 16 and 17, the magnetic pipette of the present embodiment operates on the principle that (taking a blood sample as an example): 1) Adding a blood sample into the lysis solution hole, and repeatedly sucking and discharging by using a magnetic suction pipette; 2) After heating the lysate well for a period of time, the cells will be destroyed by the lysate, releasing DNA; 3) Sucking the solution in the cracking solution hole by using a magnetic pipette, discharging the solution to a magnetic bead mixed solution hole, and repeatedly sucking and discharging by using the magnetic pipette; 4) After standing for a period of time, the DNA can be specifically combined with the magnetic beads; 5) Sucking the solution in the magnetic bead mixed solution hole by using a magnetic pipette, wherein the solution is positioned in a gun head on a pipetting assembly; 6) Starting a magnetic attraction motor to drive the connecting rod to rotate so that a magnet on the connecting rod is close to a gun head on the pipetting assembly and adsorbs magnetic beads in the gun head; 7) Discharging the solution in the gun head on the pipetting assembly to a magnetic bead mixed solution hole, wherein the magnetic beads containing DNA are attracted to the vicinity of the magnet on the magnetic attraction assembly; 8) Moving the magnetic pipette to a washing liquid hole, starting a magnetic motor to drive a connecting rod to rotate so that a magnet on the connecting rod is far away from a gun head on a pipetting assembly, and removing the adsorption of magnetic beads in the gun head; 9) Repeatedly sucking and discharging by using a magnetic sucking pipettor to wash the magnetic beads; 10 Starting the magnetic attraction motor to drive the connecting rod to rotate so that the magnet on the connecting rod is close to the gun head on the pipetting assembly and the magnetic beads in the gun head are adsorbed again; 11 Discharging the solution in the gun head on the pipetting assembly to a wash port where the magnetic beads containing DNA are re-attracted near the magnet on the magnetic assembly; 12 Moving the magnetic pipette to the eluent hole, starting the magnetic motor to drive the connecting rod to rotate so that the magnet on the connecting rod is far away from the gun head on the pipetting assembly, and removing the adsorption of the magnetic beads in the gun head again; 13 Repeatedly sucking and discharging the solution in the eluent hole by using a magnetic suction pipette, so that the magnetic beads containing DNA enter the eluent hole; 14 Heating the eluent hole to separate the magnetic beads from the DNA; 15 Sucking the solution in the eluent hole by using a magnetic suction pipettor, starting a magnetic suction motor to drive a connecting rod to rotate so that a magnet on the connecting rod is close to a gun head on a pipetting assembly, and re-adsorbing magnetic beads in the gun head; 16 The solution in the tip of the pipette assembly is discharged to the DNA sample well to obtain a DNA solution.
Capillary electrophoresis system
As shown in fig. 18 to 36, which are a preferred example of the capillary electrophoresis system in the present invention. In this embodiment, the capillary electrophoresis system 2 comprises a mounting bracket, on which the capillary assembly 600 is disposed, wherein a motion platform assembly 700 is disposed on the mounting bracket at a position corresponding to the cathode end of the capillary assembly 600, and the motion platform assembly 700 can connect the electrophoresis assembly 135 in the PCR reaction zone 130 with the cathode end of the capillary assembly 600, so as to contact the cathode buffer, water or sample with the cathode end of the capillary as required; a glue filling assembly 800 is arranged on the mounting bracket at a position corresponding to the anode end of the capillary tube assembly 600, the glue filling assembly 800 is connected with the anode end of the capillary tube assembly 600, and anode buffer can be contacted with the anode end of the capillary tube according to requirements to fill gel into the capillary tube; an optical detection assembly 900 is arranged on the mounting bracket at a position corresponding to the detection window of the capillary assembly 600, and the optical detection assembly 900 is connected with the detection window of the capillary assembly 600 for realizing detection analysis of capillary electrophoresis.
Further, as shown in fig. 19, the capillary tube assembly 600 includes a shielding member, a temperature control member and a capillary tube 630, the temperature control member and the capillary tube 630 being disposed inside the shielding member, the temperature control member and the capillary tube 630 being attached together. The capillary 630 may be manufactured by using commercially available products, such as elastic fused silica capillary manufactured by Polymicro Technologies (PT), which is typically manufactured by drawing artificial fused silica semi-finished products, and similar products may be manufactured by using natural quartz, borosilicate glass, various plastics or synthetic materials of fused silica materials, which mainly depend on practical application requirements.
Further, the capillary 630 is preferably curved and disposed inside the protecting element as a carrier for electrophoresis separation, so as to form a smooth arc for electrophoresis separation, and of course, the capillary 630 may be disposed inside the protecting element in other manners, such as directly disposing a linear capillary inside the protecting element. In addition, in the present embodiment, only one capillary tube is provided in one capillary tube assembly, but according to actual needs, for example, in order to improve the analysis throughput or the analysis efficiency, a plurality of capillary tubes may be arranged in parallel in a capillary tube bundle, for example, 4, 8, 16, 24 or 32 capillary tubes are provided in an array in the capillary tube assembly, which is not particularly limited in the present invention.
Further, the protection element mainly plays a role of protecting the capillary 630, and includes a first housing 611 and a second housing 612, the first housing 611 and the second housing 612 are connected to each other to form a closed chamber, and the capillary 630 is directly placed in the closed chamber, so that the protection element and the capillary 630 form a whole, thereby not only protecting the capillary from damage, but also effectively improving the replacement mode of the capillary. Preferably, one ends of the first housing 611 and the second housing 612 are hinged to each other, and the other ends thereof are openable and lockable in a locking manner, so as to facilitate maintenance and replacement of the capillary tube.
Further, the temperature control element includes a heating sheet 621, a heat conducting sheet 622 and an insulating sheet 623 connected in sequence, in this embodiment, as shown in fig. 19, the heating sheet 621, the heat conducting sheet 622 and the insulating sheet 623 are sequentially disposed between the capillary tube 630 and the second housing 612, the heating sheet 621 is close to the second housing 612, and the insulating sheet 623 is close to the capillary tube 630, wherein the heating sheet 621 can ensure the temperature of the capillary tube 630 during electrophoresis, and preferably, a temperature sensor is disposed at the heating sheet 621 to feed back the temperature of the heating sheet 621 in real time; the heat conductive sheet 622 can uniformly and sufficiently conduct the temperature of the heating sheet 621 to the entire capillary 630; the insulating sheet 623 can conduct heat and has an insulating effect during high voltage electrophoresis, preventing the occurrence of discharge phenomena such as arcing. In addition, a temperature sensor is preferably also provided at the capillary 630 to feed back the temperature of the capillary 630 in real time.
Optionally, the temperature control element may also be heated by adopting a hot air circulation mode, specifically, the capillary tube is assembled in the heat insulation shell, the heat insulation shell is provided with an air inlet and an air outlet, hot air is generated by a heating plate and a fan in the heating furnace, the hot air enters the internal cavity of the heat insulation shell from the air inlet, heats the capillary tube in the heat insulation shell, is discharged from the air outlet, and reenters the heating furnace, preferably, the temperature can be fed back and regulated by detecting the temperature of the heating plate, the air inlet and the air outlet.
Further, as shown in fig. 20, the motion stage assembly 700 is provided on the mounting bracket at a position corresponding to the cathode end of the capillary assembly 600, and includes a driving motor 710, a slider 720, a sliding rail 730, and a carrying stage 740. Wherein, the driving motor 710 is fixedly arranged on the mounting bracket, the motor shaft of the driving motor 710 is connected with the sliding block 720, the sliding block 720 is slidably arranged on the sliding rail 730, the sliding rail 730 is fixedly arranged on the mounting bracket, the sliding block 720 is connected with the bearing platform 740, the electrophoresis component 135 in the PCR reaction zone 130 can be arranged on the bearing platform 740, and cathode buffer solution (conductive medium during electrophoresis), water (medium for discharging waste rubber during glue filling) or a sample and the like can be added into the electrophoresis component 135 according to the requirement.
Therefore, the driving motor 710 can drive the slider 720 to move upwards along the sliding rail 730, so as to drive the carrying platform 740 on the slider 720 to approach the cathode end of the capillary assembly 600, and further make the cathode end of the capillary contact with the reagent in the electrophoresis assembly 135 on the carrying platform 740; the driving motor 710 can drive the slider 720 to move downward along the sliding rail 730, so as to drive the carrying platform 740 on the slider 720 to be far away from the cathode end of the capillary assembly 600, and further separate the electrophoresis assembly 135 on the carrying platform 740 from the cathode end of the capillary assembly 600, so as to facilitate replacement of the electrophoresis assembly 135.
In addition, according to actual needs, the devices such as a motor and a sliding rail can be added to the motion platform assembly to be changed into a two-dimensional or three-dimensional motion platform, so that the degree of automation is increased. For example, after the two-dimensional motion platform is formed, the reagent tube can be replaced manually, so that the operation is reduced; after the sample is formed into a three-dimensional motion platform, a plurality of reagent tubes, or 8-row or 96-well plates and the like can be arranged so as to realize the purpose of continuous sample loading.
Further, as shown in fig. 21, a glue dispensing assembly 800 is provided on the mounting bracket at a location corresponding to the anode end of the capillary tube assembly 600, including a glue dispensing motor 801, a slider 802, a slide rail 803, a syringe 804, a glue block element 805, and an anode buffer bottle 806. Wherein, glue-pouring motor 801 is fixed to be set up on the installing support, and glue-pouring motor 801's motor shaft links to each other with slider 802, and slider 802 slides and sets up on slide rail 803, and slide rail 803 is fixed to be set up on the installing support, and slider 802 links to each other with the push rod on the syringe 804, and syringe 804 is used for temporarily storing the gel and realizes the capillary glue-pouring.
Further, the glue block element 805 is fixedly disposed on the mounting bracket, three first channels, second channels and third channels which are mutually communicated are disposed in the glue block element 805, wherein the first channels are communicated with the injector 804, the second channels are communicated with the anode buffer solution bottle 806, the third channels are communicated with the capillary 630, an on-off valve 807 is disposed between the second channels and the anode buffer solution bottle 806 to control the second channels to be communicated with or disconnected from the anode buffer solution bottle 806, the anode buffer solution bottle 806 is used for temporarily storing anode buffer solution, and the anode buffer solution is a conductive medium during electrophoresis.
Therefore, when the glue is required to be filled, the on-off valve 807 between the second channel in the glue block element 805 and the anode buffer solution bottle 806 is closed, so that the second channel and the anode buffer solution bottle 806 are in an off state, the glue filling motor 801 drives the sliding block 802 to move downwards along the sliding rail 803, so that the pushing rod in the injector 804 is pushed to move downwards by the sliding block 802, the gel in the injector 804 enters the first channel in the glue block element 805, and the capillary 630 is injected through the third channel, so that the glue filling operation is completed.
Further, as shown in fig. 22 and 23, another embodiment of the glue dispensing assembly 800 of the present invention is illustrated. The difference from the previous embodiment is that in this embodiment, the outside of the syringe 804 is provided with a refrigerating element 810 to enable the gel to be preserved for a long time. Specifically, the refrigeration element 810 includes a first fixing member 811 and a second fixing member 812, the first fixing member 811 is connected with the second fixing member 812 to form a closed chamber, the syringe 804 is located in the closed chamber, the heat conducting member 813 is arranged on the outer side of the syringe 804 in a coating mode, the heat conducting member 813 is connected with the TEC refrigeration piece 814, the heat insulating member 815 is arranged on the outer side of the heat conducting member 813 in a coating mode, and therefore the temperature in the syringe 804 can be adjusted through the TEC refrigeration piece 814 and the heat conducting member 813, heat dissipation can be reduced through the heat insulating member 815, and temperature adjustment efficiency is improved.
In addition, in order to increase the heat dissipation rate, it is preferable that openings are formed at positions of the heat preservation member 815 and the first fixing member 811 corresponding to the TEC cooling fins 814, the TEC cooling fins 814 can be connected with the heat dissipation fins 816 through the openings, and the heat dissipation fins 816 are connected with the heat dissipation fans 817, so that the TEC cooling fins 814 can be assisted to be cooled through the heat dissipation fans 817 and the heat dissipation fins 816, and further, the temperature adjustment efficiency is improved.
Further, as shown in fig. 24 to 33, another embodiment of the glue-pouring assembly according to the present invention is shown. Compared with the above embodiment, in this embodiment, the glue storage mode, the glue block structure, the glue filling mode, and the like are all optimized for more integration and automation.
Specifically, in the present embodiment, the glue dispensing assembly includes a support member 820, a storage member 830, and a glue block member 840, wherein the support member 820 is a base assembly for providing frame support for the entire glue dispensing assembly; the storage element 830 is disposed on the support element 820, and includes a gel storage cavity 831 and a buffer storage cavity 832, wherein gel required for capillary electrophoresis is stored in the gel storage cavity 831, and anode buffer required for capillary electrophoresis is stored in the buffer storage cavity 832; the gel block 840 has a plurality of connection channels connected to the buffer storage chamber 832, the gel storage chamber 831, the capillary tube, and the filling driving element 850, respectively, to allow gel filling in the capillary tube 630 through the gel block 840.
Further, as shown in fig. 28, the support member 820 includes a post 821, a carrying table 822 is slidably disposed on the post 821, and the storage member 830 is disposed on the carrying table 822, wherein the carrying table 822 includes a first carrying portion 823 and a second carrying portion 824, the first carrying portion 823 is used for carrying a buffer solution storage chamber 832 in the storage member 830, and the second carrying portion 824 is used for carrying a gel storage chamber 831 in the storage member 830. In addition, the carrying platform 822 is connected to the driving unit 825, and the driving unit 825 can drive the carrying platform 822 to move up and down along the upright post 821, so as to facilitate the replacement of the storage element 830, and in this embodiment, the driving unit 825 can employ a motor.
Further, as shown in fig. 29, the storage element 830 is in an integral structure, that is, the gel storage chamber 831 and the buffer storage chamber 832 are connected to each other to form a whole, so that when the storage element 830 needs to be replaced, the carrying table 822 in the motor-driven support element 820 descends, and the replacement can be completed by removing the integral storage element 830 from the carrying table 822, which is convenient and trouble-free. Of course, according to practical needs, the storage element 830 may be made into a split structure, that is, the gel storage chamber 831 and the buffer storage chamber 832 are two independent structures, so that flexibility of use can be increased.
Further, as shown in fig. 26 and 27, the gel storage chamber 831 is connected to the refrigerating element 860, and the refrigerating element 860 can control the temperature in the gel storage chamber 831 to ensure the low temperature storage of the gel, in this embodiment, the refrigerating element 860 is disposed on the second bearing part 824 of the support member 820, and the gel storage chamber 831 can be in contact with the refrigerating element 860 when placed on the second bearing part 824. Meanwhile, the heat preservation element 870 is further arranged outside the gel storage cavity 831, the heat preservation element 870 and the refrigerating element 860 are matched for use, so that the gel can be stored for a long time, frequent replacement and filling of the gel are avoided, the process cost is saved, meanwhile, the filling of the gel can be realized only by replacing the storage element 830, and the complexity of operation is reduced. It should be noted that the refrigeration element 860 and the thermal insulation element 870 may be made of refrigeration structures and thermal insulation materials commonly used in the art, which are not particularly limited in the present invention.
Further, as shown in fig. 30 to 33, the adhesive block member 840 has a block structure, in which a first connection channel 841, a second connection channel 842, a third connection channel 843, and a fourth connection channel 844 are provided in the adhesive block member 840, and the four connection channels are connected to each other, preferably, as shown in fig. 32 and 33, the first connection channel 841, the second connection channel 842, the third connection channel 843, and the fourth connection channel 844 have one common communication convergence point 845, through which the communication with each other is achieved.
Further, the first connection channel 841 communicates with the gel storage chamber 831, the second connection channel 842 communicates with the buffer storage chamber 832, the third connection channel 843 communicates with the capillary tube, and the fourth connection channel 844 communicates with the priming drive member 850. Among them, it is preferable that a check valve (not shown) is provided between the first connection passage 841 and the gel storage chamber 831, the check valve allowing only the gel to flow from the gel storage chamber 831 into the first connection passage 841; an on-off valve 846 is arranged between the second connection channel 842 and the buffer storage cavity 832, and the on-off valve 846 can control the connection and disconnection between the second connection channel 842 and the buffer storage cavity 832; the infusion drive unit 850 is a syringe as is commonly used in the art, as shown in fig. 25, to power the infusion of the gel.
Thus, when gel is to be poured into the capillary tube, the on-off valve 846 between the second connection channel 842 and the buffer storage cavity 832 is closed to disconnect the second connection channel 842 from the buffer storage cavity 832, the syringe is driven to provide suction, and the gel in the gel storage cavity 831 flows into the first connection channel 841 through the check valve and then flows into the fourth connection channel 844 and the syringe 804 through the communication collection point 845; by driving the syringe 804 to provide the pushing force, the gel in the fourth connecting channel 844 and the syringe 804 flows into the second connecting channel 842 and the third connecting channel 843 through the communication manifold 845, and the gel is poured into the channel between the buffer storage chamber 832 and the capillary.
Further, as shown in fig. 34 to 36, it is a preferable example of the optical detection element. In this embodiment, the optical detection assembly 900 is disposed on the mounting bracket at a position corresponding to the detection window of the capillary assembly 600, and includes a mounting plate 901, the mounting plate 901 being of a rectangular structure, the laser 902, the first mirror 903, the second mirror 904, the focusing lens 905, the capillary unit 906, the detection objective 907, and the third mirror 908 being disposed at edge positions of the mounting plate 901, and the filter 909, the sleeve lens 910, and the spectrometer 911 being located at intermediate positions of the mounting plate 901. Thus, the excitation light beam in the optical detection assembly 900 propagates between the assemblies located at the edge positions of the mounting base plate, and irradiates the capillaries in the capillary unit 906 to generate fluorescence, which propagates between the assemblies located at the intermediate positions of the mounting base plate, and finally enters the spectrometer to complete detection analysis.
Further, as shown in fig. 34 and 35, the laser 902 is disposed at one side edge of the mounting plate 901, and preferably the laser 902 is disposed extending along a first long side 912 of the mounting plate 901, wherein the laser 902 is configured to provide an excitation light beam 916, and the excitation light beam 916 propagates along the first long side 912 of the mounting plate 901, and the excitation light may interact with a fluorescent agent in the capillary tube to generate fluorescence, thereby implementing optical detection of capillary electrophoresis.
Further, a first reflecting mirror 903 is disposed on the mounting base 901 at a position near the emitting end of the laser 902, where a first reflecting angle is formed between the reflecting surface of the first reflecting mirror 903 and the excitation light beam 916 emitted by the laser 902, and the first reflecting angle can make the excitation light beam 916 reflect to the subsequent second reflecting mirror 904 through the first reflecting mirror 903, and preferably, the first reflecting angle is 45 ° so that the excitation light beam 916 is reflected at a right angle at the first reflecting mirror 903. Specifically, as shown in fig. 34 and 36, the first reflecting mirror 903 is disposed at a first corner of the mounting board 901, that is, at the boundary between the first long side 912 and the first short side 913, whereby the excitation light beam 916 emitted by the laser 902 along the first long side 912 of the mounting board 901 can be reflected by the first reflecting mirror 903 to become a primary reflected light beam 917 propagating along the first short side 913 of the mounting board 901.
Further, as shown in fig. 35 and 36, the second reflecting mirror 904 is disposed at a second corner of the mounting board 901, that is, at the boundary between the first short side 913 and the second long side 914, and a second reflection angle is formed between the primary reflected light beam 917 reflected by the first reflecting mirror 903 and the reflecting surface of the second reflecting mirror 904, and the second reflection angle may enable the primary reflected light beam 917 to be reflected onto the subsequent focusing lens 905 by the second reflecting mirror 904, preferably, the second reflection angle is also 45 ° so that the primary reflected light beam 917 is also reflected at a right angle at the second reflecting mirror 904.
Further, as shown in fig. 35 and 36, a focusing lens 905 and a capillary unit 906 are disposed on the second long side 914 of the mounting board 901, wherein the focusing lens 905 is disposed between the second mirror 904 and the capillary unit 906, and is capable of receiving the secondary reflected light beam 918 reflected by the second mirror 904, forming a focused light beam 919, and then irradiating the focused light beam onto a capillary in the capillary unit 906, specifically, an optical detection window on the capillary, so as to generate fluorescence. In particular, the capillary unit 906 may be located at a third corner of the mounting base 901, i.e., at the intersection of the second long side 914 and the second short side 915.
Further, a detection objective 907 is provided with the capillary unit 906, specifically, the detection objective 907 is disposed opposite to an optical detection window on the capillary to collect the fluorescent light beam 920 emitted at the optical detection window. In addition, the third reflecting mirror 908 is disposed at the light exit of the detection objective 907, wherein a third reflecting angle is formed between the reflecting surface of the third reflecting mirror 908 and the fluorescent light beam 920 emitted from the detection objective 907, and the third reflecting angle may enable the fluorescent light beam 920 to be reflected onto the subsequent optical filter 909 and sleeve lens 910 through the third reflecting mirror 908, preferably, the third reflecting angle is 45 °, so that the fluorescent light beam 920 is reflected at a right angle at the third reflecting mirror 908.
Further, a light filter 909 is disposed at a light inlet of the sleeve lens 910, and a light outlet is connected to the spectrometer 911, where the light filter 909 is used to filter out an impurity light beam (such as an excitation light beam) in the tertiary reflection light beam 921 entering the sleeve lens 910, so as to form a detection light beam, so as to ensure accuracy of detection analysis; the sleeve lens 910 is used to refocus the detection beam and transmit it to the spectrometer 911; the spectrometer 911 is used to perform spectral analysis on the focused detection beam.
Thus, as shown in fig. 36, the optical detection assembly 900 of the present invention operates as follows: 1) The laser 902 emits an excitation beam 916; 2) The excitation light beam 916 is reflected by the first mirror 903 to form a primary reflected light beam 917; 3) Primary reflected beam 917 impinges on second mirror 904 forming secondary reflected beam 918; 4) The secondary reflected beam 918 impinges on a focusing lens 905 to form a focused beam 919; 5) The focused beam 919 impinges on the capillaries in the capillary unit 906, producing fluorescence; 6) The detection objective 907 collects the fluorescent light beam 920 generated in the capillary; 7) The fluorescent light beam 920 is irradiated onto the third mirror 908, forming a tertiary reflected light beam 921; 8) The tertiary reflected light beam 921 is irradiated onto the filter 909, forming a detection light beam; 9) The detection beam is focused by the sleeve lens 910 and then transmitted to the spectrometer 911 for detection and analysis.
Further, it is preferable that at least one of the first mirror 903 and the third mirror 908 is disposed on an adjustable lens stage, that is, the angles of the first mirror 903 and the third mirror 908 can be adjusted by the adjustable lens stage, so that adjustment is convenient, assembly accuracy is reduced, for example, when the angle of the second mirror 904 is 45.5 degrees due to assembly error, the optical path of the second mirror 904 can be made to enter the lens by adjusting the angle of the first mirror by 0.5 degrees. The adjustable lens table may adopt an angle fine adjustment structure commonly known in the art, and the invention is not limited thereto.
According to the invention, all steps of DNA detection and analysis are integrated on one miniaturized device, so that the operation is convenient, the detection is rapid, the efficiency of DNA detection is greatly improved on the premise of ensuring the accuracy, and meanwhile, the portability of movement is greatly improved by the integrated miniaturized device, and the range of applicable places is enlarged.
The invention has been further described with reference to specific embodiments, but it should be understood that the detailed description is not to be construed as limiting the spirit and scope of the invention, but rather as providing those skilled in the art with the benefit of this disclosure with the benefit of their various modifications to the described embodiments.

Claims (14)

1. An integrated DNA analyzer is characterized by comprising an analyzer shell, wherein a sample processing system and a capillary electrophoresis system are arranged in the analyzer shell;
the sample processing system comprises a sample extraction area, a PCR reaction area and a liquid shifter, wherein the liquid shifter can move between the sample extraction area and the PCR reaction area so as to finish DNA extraction of a sample in the sample extraction area and finish PCR reaction of the extracted DNA in the PCR reaction area, and an electrophoresis component is arranged in the PCR reaction area;
The capillary electrophoresis system comprises a capillary component, wherein a motion platform component is arranged at the cathode end of the capillary component, the motion platform component can connect the electrophoresis component in the PCR reaction zone with the cathode end of the capillary component, the anode end of the capillary component is connected with a glue filling component, and an optical detection component is arranged at a detection window of the capillary component;
the liquid transfer device comprises a bottom plate, an injection motor and an injector, wherein the injection motor and the injector are arranged on the bottom plate, a transmission pressing plate is arranged on a motor shaft of the injection motor, the transmission pressing plate is connected with a push rod of the injector, and a gun head is connected with the injector;
The bottom plate is fixedly provided with a first baffle and a second baffle, the first baffle is close to the injection motor, the second baffle is close to the gun head, the supporting rod is arranged between the first baffle and the second baffle, one end of the supporting rod is fixedly connected with the first baffle, and the other end of the supporting rod is fixedly connected with the second baffle;
A gun head pressing frame is sleeved on one side, close to the second baffle, of the supporting rod, the gun head pressing frame comprises a first pressing plate and a second pressing plate, a connecting rod is arranged between the first pressing plate and the second pressing plate, the first pressing plate is sleeved on the supporting rod and positioned between the first baffle and the second baffle, the connecting rod penetrates through the second baffle to be arranged, the second pressing plate is positioned between the second baffle and the gun head, a reset spring is sleeved on the connecting rod between the first pressing plate and the second pressing plate, one end of the reset spring is in contact with the first pressing plate, and the other end of the reset spring is in contact with the second baffle;
The transmission clamp plate cover is established on the bracing piece, can be relative bracing piece reciprocating motion, and the cover is equipped with the transmission sleeve on the bracing piece, and the transmission sleeve is located between transmission clamp plate and the first clamp plate, and transmission sleeve's one end contacts with the transmission clamp plate, and the other end contacts with the first clamp plate.
2. The integrated DNA analyzer of claim 1, wherein the sample processing system comprises a processing device comprising a mounting plate having a partition disposed thereon, the partition having a sample extraction zone on one side and a PCR reaction zone on the other side.
3. The integrated DNA analyzer of claim 1 or 2, wherein the PCR reaction zone comprises a PCR reaction assembly, the PCR reaction assembly comprises a reaction tank unit and a temperature control unit, the temperature control unit comprises a TEC temperature control assembly, the reaction tank unit is arranged above the TEC temperature control assembly, a radiator is arranged below the TEC temperature control assembly, a heat transfer groove is formed at the bottom of the radiator, one end of the heat transfer sheet is arranged in the heat transfer groove, and the other end of the heat transfer sheet is connected with the heat radiation fan.
4. The integrated DNA analyzer of claim 1 or 2, wherein the electrophoresis assembly in the PCR reaction zone comprises a sample tube, a wash tube, and a buffer tube, wherein the sample tube, the wash tube, and the buffer tube respectively store reagents and samples used in the capillary electrophoresis process.
5. The integrated DNA analyzer of claim 1 or 2, wherein the sample processing system comprises a pipetting device comprising a support frame disposed above the sample extraction zone and the PCR reaction zone, a movement device disposed on the support frame, and a pipetting device movable on the support frame by the movement device.
6. The integrated DNA analyzer of claim 1, wherein the pipette is provided with a magnetic attraction assembly, the magnetic attraction assembly comprises a magnetic attraction motor and a magnet connected with the magnetic attraction motor, and the magnetic attraction motor can drive the magnet to rotate so as to approach or separate from the gun head, thereby completing the adsorption and desorption of the magnetic beads in the gun head.
7. The integrated DNA analyzer of claim 1, wherein the capillary tube assembly comprises a guard element, a temperature control element, and a capillary tube, the temperature control element and the capillary tube being disposed within the guard element, the temperature control element and the capillary tube being affixed together.
8. The integrated DNA analyzer of claim 1 or 7, wherein the motion platform assembly comprises a drive motor, a slide block, a slide rail and a carrying platform, wherein a motor shaft of the drive motor is connected with the slide block, the slide block is slidably disposed on the slide rail, the slide block is connected with the carrying platform, and the electrophoresis assembly in the PCR reaction zone is disposed on the carrying platform.
9. The integrated DNA analyzer of claim 1 or 7, wherein the glue filling assembly comprises an injector, a glue block element and an anode buffer liquid bottle, wherein a first channel, a second channel and a third channel which are communicated with each other are arranged in the glue block element, the first channel is communicated with the injector, the second channel is communicated with the anode buffer liquid bottle, the third channel is communicated with a capillary tube, an opening and closing valve is arranged between the second channel and the anode buffer liquid bottle, a heat conducting piece is arranged on the outer side of the injector in a wrapping mode, the heat conducting piece is connected with a TEC refrigerating piece, a heat insulating piece is arranged on the outer side of the heat insulating piece in a wrapping mode, an opening is formed in the heat insulating piece and the fixing piece at a position corresponding to the TEC refrigerating piece, the TEC refrigerating piece is connected with a radiating fin through the opening, and the radiating fin is connected with a radiating fan.
10. The integrated DNA analyzer of claim 1 or 7, wherein the gel filling assembly comprises a support member, a storage member and a gel block member, the storage member is disposed on the support member and comprises a gel storage chamber and a buffer storage chamber, the gel storage chamber is connected with the refrigerating member, a plurality of connecting channels are disposed in the gel block member, and the plurality of connecting channels are respectively connected with the buffer storage chamber, the gel storage chamber, the capillary tube and the filling driving member.
11. The integrated DNA analyzer of claim 10, wherein the support member comprises a post, the post is slidably provided with a carrying platform, the storage member is disposed on the carrying platform, the carrying platform is connected to a driving unit, and the driving unit drives the carrying platform to reciprocate along the post.
12. The integrated DNA analyzer of claim 10, wherein the gel reservoir and the buffer reservoir are of unitary construction.
13. The integrated DNA analyzer of claim 10, wherein the gel block member has a first connecting channel, a second connecting channel, a third connecting channel, and a fourth connecting channel disposed therein, and a communication junction is disposed between the first connecting channel, the second connecting channel, the third connecting channel, and the fourth connecting channel, and is in communication with each other through the communication junction; the first connecting channel is communicated with the gel storage cavity, the second connecting channel is communicated with the buffer liquid storage cavity, the third connecting channel is communicated with the capillary tube, the fourth connecting channel is communicated with the filling driving element, a one-way valve is arranged between the first connecting channel and the gel storage cavity, and an opening and closing valve is arranged between the second connecting channel and the buffer liquid storage cavity.
14. The integrated DNA analyzer of claim 1 or 7, wherein the optical detection assembly comprises a mounting plate, and a laser, a first mirror, a second mirror, a focusing lens, a capillary assembly, a detection objective lens, and a third mirror are sequentially disposed at an edge position of the mounting plate, and an excitation beam generated by the laser irradiates a capillary in the capillary assembly through the first mirror, the second mirror, and the focusing lens to generate fluorescence; the middle position of the mounting base plate is provided with an optical filter, a sleeve lens and a spectrometer, the detection objective lens collects fluorescent light beams generated in the capillary tube, and the fluorescent light beams enter the spectrometer after passing through the third reflector, the optical filter and the sleeve lens so as to carry out detection analysis.
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