CN108603155A - A kind of system being used to prepare gene sequencing sample and its application - Google Patents
A kind of system being used to prepare gene sequencing sample and its application Download PDFInfo
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- CN108603155A CN108603155A CN201680081102.8A CN201680081102A CN108603155A CN 108603155 A CN108603155 A CN 108603155A CN 201680081102 A CN201680081102 A CN 201680081102A CN 108603155 A CN108603155 A CN 108603155A
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- 238000012163 sequencing technique Methods 0.000 title claims abstract description 51
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 47
- 239000011324 bead Substances 0.000 claims abstract description 36
- 238000010438 heat treatment Methods 0.000 claims abstract description 34
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 33
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 33
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 33
- 239000007788 liquid Substances 0.000 claims abstract description 25
- 239000002994 raw material Substances 0.000 claims abstract description 23
- 239000002699 waste material Substances 0.000 claims abstract description 23
- 230000003321 amplification Effects 0.000 claims abstract description 21
- 238000003199 nucleic acid amplification method Methods 0.000 claims abstract description 21
- 238000011084 recovery Methods 0.000 claims abstract description 20
- 238000007789 sealing Methods 0.000 claims abstract description 14
- 230000007246 mechanism Effects 0.000 claims abstract description 7
- 238000001816 cooling Methods 0.000 claims description 19
- 238000004659 sterilization and disinfection Methods 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 230000001954 sterilising effect Effects 0.000 claims description 13
- 238000000605 extraction Methods 0.000 claims description 10
- 238000005485 electric heating Methods 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 7
- 238000001821 nucleic acid purification Methods 0.000 claims description 5
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- 238000002360 preparation method Methods 0.000 abstract description 12
- 230000003028 elevating effect Effects 0.000 abstract description 5
- 238000012864 cross contamination Methods 0.000 abstract description 3
- 238000005057 refrigeration Methods 0.000 abstract description 3
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- 238000000034 method Methods 0.000 description 21
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- 238000012360 testing method Methods 0.000 description 7
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- 238000006911 enzymatic reaction Methods 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
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- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
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- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
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- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
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- 229940104230 thymidine Drugs 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
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- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
- C12M1/38—Temperature-responsive control
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Abstract
This application discloses a kind of system being used to prepare gene sequencing sample and its applications.The system of the application, including seal cavity that shell surrounds, and the raw material placement module, nucleic acid amplification module, heating refrigeration module, liquid relief module, magnetic beads for purifying module, waste recovery module and the control module that are located in seal cavity；Housing top end sets air inlet, installs air filter unit；Liquid relief module includes automatic liquid-transfering gun and controls the mechanical arm of automatic liquid-transfering gun movement；It includes alternating temperature porous plate, room temperature porous plate to heat refrigeration module；Nucleic acid amplification module includes heating sealing cover, PCR porous plates, radiator and exhaust fan；Magnetic beads for purifying module includes purifying porous plate, holder, magnetic frame and elevating mechanism, each assembly operating of control module independent control.The system of the application, realizes one-stop automation sample preparation, and the exportable library sample for sequencing after input sample avoids environmental pollution and sample cross contamination, improves sequencing sample quality and efficiency.
Description
Specification denomination of invention: a kind of system being used to prepare gene sequencing sample and its applied technical field
[0001] this application involves gene sequencing fields, more particularly to a kind of system and its application for being used to prepare gene sequencing sample.
[0002]
[0003] background technique
[0004] gene sequencing or nucleic acid sequencing are to study one of the important method of nucleic acid, including DNA sequencing and RN A are sequenced.DNA sequencing (DNA sequencing, or translate DNA sequencing) refer to analysis specific DNA fragments base sequence, that is, adenine (A), thymidine (T), cytimidine (C) and guanine (G) arrangement mode.Likewise, RNA sequencing refers to the base sequence for analyzing specific RNA segment, that is, adenine (A), guanine (G), cytimidine (C) and uracil (U) arrangement mode.
[0005] before carrying out gene sequencing, it needs first from the source substance containing gene molecule, such as blood plasma, tissue samples or cell culture etc., middle extraction nucleic acid molecules, then expand nucleic acid molecules, are usually expanded using polymerase chain reaction (abbreviation PCR), then nucleic acid molecules are purified again, the library of gene sequencing finally can be just obtained, which is sequenced as gene sequencing sample for sequenator.Sequencing library whole process, which is obtained, from nucleic acid extraction, PCR amplification to purifying is referred to as gene sequencing sample preparation.
[0006] in the preparation process of gene sequencing sample, nucleic acid extraction, PCR amplification, nucleic acid purification etc. are to operate progress by hand fit respectively on different instruments.Such as nucleic acid extraction, it needs repeatedly to use centrifuge, every time after the completion of centrifugation, by manually taking out centrifuge tube, removal or reservation supernatant, adds reagent and be centrifuged, repeatedly.And PCR amplification process is also to need the good reaction solution of human configuration, response procedures are set in PCR instrument, then the DNA of preparation is manually added in reaction solution, it is manually placed in PCR instrument and is expanded, after the completion of amplification, it is manually drawn off again, reagent is added into amplified production and is purified.Likewise, nucleic acid purification needs to use other instrument and equipments and reagent again.
[0007] as it can be seen that the process flow of preparation gene sequencing sample is complicated, consumes inch；And since dosage, placement program, operating environment etc. of the test process to various reagents solution have strict requirements, and current processing mode is nearly all that manual operation is completed, and mistake or error inevitably occurs；Importantly, addition or sample in reagent
In this transfer process, manual operation be easy to cause cross contamination, influences gene sequencing result.Furthermore, in the process flow of existing gene sequencing sample, the equipment of each experimental stage is all independent completion special test link, such as centrifugation, PCR amplification etc., manual operation is needed to be shifted in whole process, program complexity, is easy error at heavy workload, and multiple devices need to occupy larger space.
[0008]
[0009] summary of the invention
[0010] purpose of the application is to provide a kind of system and its application for being used to prepare gene sequencing sample.
[0011] to achieve the goals above, the application uses following technical scheme:
[0012] a kind of system for being used to prepare gene sequencing sample of the one side public affairs Jian of the application, the seal cavity surrounded including one by shell 1, and be arranged in the intracorporal raw material placement module 2 of seal chamber, nucleic acid amplification module 3, heating and cooling module 4, liquid relief module, magnetic beads for purifying module 6, waste recovery module and control module；The top Jian of shell 1 is equipped with air inlet 11, also, in being equipped with air filter unit 12 in air inlet 11, to ensure that the intracorporal air of seal chamber is clean；Liquid relief module includes automatic liquid-transfering gun 51 and mechanical arm 52, and automatic liquid-transfering gun 51 is set on mechanical arm 52, and mechanical arm 52 controls the automatic movement of liquid-transfering gun 51, and automatic liquid-transfering gun 51 is for drawing and transfer liquid sample；Heating and cooling module 4 includes electric heating assembly, with the alternating temperature porous plate 41 being set on electric heating assembly, room temperature porous plate 42, and it is set to the exhaust fan 43 and radiating subassembly 44 of 42 lower section of alternating temperature porous plate 41 and room temperature porous plate, electric heating assembly is independent to give alternating temperature porous plate 41, room temperature porous plate 42 heats, usually, alternating temperature porous plate 41 can provide different temperature according to setting, and then the temperature remains within the normal range for room temperature porous plate 42, alternating temperature porous plate 41 and room temperature porous plate 42 are for placing different sample and reagent, exhaust fan 43 and radiating subassembly 44 are used to control the temperature of alternating temperature porous plate 41 and room temperature porous plate 42；Nucleic acid amplification module 3 includes heating sealing cover 31, PCR porous plate 32, radiator 33 and exhaust fan 34, heating sealing cover 31 seals PCR porous plate 32 in progress PCR reaction inch, and it is heated, PCR porous plate 32 is used for placing response liquid, radiator 33 and exhaust fan 34 for controlling reaction temperature；Magnetic beads for purifying module 6 includes purifying porous plate 61, bracket 62, magnetic frame 63 and elevating mechanism 64, purifying porous plate 61 is placed on bracket 62, the independent underface for being set to purifying porous plate 61 of magnetic frame 63, also, elevating mechanism 64 controls magnetic frame 63 and independently rises or falls；Waste recovery module includes at least one waste recovery box 71;Control module is connect with nucleic acid amplification module 3, heating and cooling module 4, liquid relief module by signal respectively, and independent control nucleic acid amplification module 3, heating and cooling module 4 or mechanical arm 52 are run.
[0013] preferably, mechanical arm 52 is provided with three moving directions, i.e. X-axis, y-axis and z-axis, mechanical arm 52 controls automatic liquid-transfering gun 51 and arbitrarily move on three directions in X-axis, y-axis and z-axis；With this same inch, raw material placement module 2, nucleic acid amplification module 3, heating and cooling module 4, magnetic beads for purifying module 6 and waste recovery module, the X-axis along mechanical arm 52 is sequentially arranged.
[0014] it should be noted that, the key of the application is for nucleic acid extraction, PCR amplification and magnetic beads for purifying etc. to be organically integrated into a system, utilize the mobile automatic liquid-transfering gun of mechanical arm, carry out reagent addition and sample transfer, whole process carries out in a ultra-clean seal cavity, manually-operated mistake or error are avoided, also avoids pollution of the environmental factor to gene sequencing sample with inch.It is understood that, the reagent of the application adds and sample transfer is realized by mechanical arm, therefore, raw material placement module 2, nucleic acid amplification module 3, heating and cooling module 4, magnetic beads for purifying module 6 and waste recovery module, it is sequentially to be arranged along the X-axis of mechanical arm 52, to facilitate the mobile sampling of mechanical arm；Y-axis as mechanical arm is horizontal vertical in X-axis, and X-axis is defined as length direction, then y-axis is exactly to realize the displacement of mechanical arm in the direction of the width, and z-axis is then that the automatic liquid-transfering gun of control moves up and down, to carry out imbibition sampling.
[0015] it should be noted that, the raw material placement module of the application is for placing the liquid samples such as blood plasma or cell culture fluid, as for solid-state sample as tissue or solid culture, the raw material placement module of the application system can be just put into after needing simply to be shredded or ground outside.
[0016] preferably, in the system of the application, ultraviolet sterilization lamp 9 is also equipped in the seal cavity that shell 1 surrounds, for carrying out ultraviolet sterilization disinfection to seal cavity.
[0017] it is understood that, in addition to using air filter unit keep seal cavity in air it is clean other than, ultraviolet disinfection disinfection is also common in laboratory, therefore, ultraviolet sterilization lamp 9 is equally installed in the system of the application, it can be with reference to equipment such as superclean benches as the specific installation site of ultraviolet lamp.
[0018] preferably, be equipped with before shell 1 one can Jian close perspective safety door 13.
[0019] preferably, two side Jian of shell 1 are equipped with see-through window 14.
[0020] it should be noted that in the application before shell, side, back etc. be to be defined according to test inch is carried out in face of the face of operator, that is to say, that the face of positive operation personnel is front.
[0021] preferably, safety door 13 and see-through window 14 is had an X-rayed all to prepare using dark brown transparent material.
[0022] it should be noted that preparing perspective safety door 13 and see-through window 14 using dark brown transparent material, it is on the one hand to facilitate observation, same inch can also be to avoid ultraviolet light to external radiation.It is appreciated that other can reach
The material of the function may be used to the application.
[0023] preferably, liquid relief module further includes two suction nozzle placement modules 53,54, for placing suction nozzle.
[0024] preferably, the back side of shell 1 is additionally provided with USB adapter 15, serial ports control interface 16, power supply Jian and closes 17 and network interface 18;The power supply Jian that power supply Jian closes 17 control whole systems is opened or is closed；USB adapter 15 and serial ports control interface 16 are for connecting controlling terminal, including computer or other human-computer interaction interfaces；Network interface 18 is used for system and network connection.
[0025] it should be noted that in order to facilitate the operation of using, the system of the application is provided with US at the back side of shell 1
B converting interface 15, serial ports control interface 16, power supply Jian close 17 and network interface 18, the connection external equipment that these interfaces can be convenient, to conveniently control and use.
[0026] preferably, the back side of shell 1 is additionally provided with thermovent 19.
[0027] preferred, the system of the application further includes external user terminal, it is sent and is instructed to control module by the user terminal, independent control raw material placement module 2, nucleic acid amplification module 3, heating and cooling module 4, liquid relief module, magnetic beads for purifying module 6 and the operation of waste recovery module.
[0028] it should be noted that user terminal can be the computer of testing crew oneself, is connected by the system of USB adapter 15, serial ports control interface 16 or network and the application, runs corresponding software on computers；It is also possible to the included independent other human-computer interaction interfaces of system, whole system is avoided to run the interference by other factors.
[0029] preferably, system further includes code reader 10, and code reader 10 is installed in the seal cavity surrounded by shell 1.
[0030] it should be noted that, the reagent of the application or various samples, all post bar code or two dimensional code on its tube wall, can be identified by the scanning of code reader 10, record corresponding sample and reagent information, for sample tracing management, operating efficiency can be effectively improved.
[0031] application of the system of the another side public affairs Jian of the application the application in nucleic acid extraction, nucleic acid purification or library construction.
[0032] it is understood that, the system of the application is used to prepare gene sequencing sample, wherein contain nucleic acid extraction, PCR, magnetic beads for purifying, certainly, in some special circumstances, the system of the application can also be individually used for nucleic acid extraction, nucleic acid purification or library construction etc..
[0033]
[0034] due to using the technology described above, the beneficial effects of the present application are as follows:
[0035] system for being used to prepare gene sequencing sample of the application, Innovation Integration is carried out to each process involved in preparation gene sequencing sample processes, realize one-stop automation sample preparation procedure, after input sample, other than midway needs progress is artificial quantitatively, the library sample for sequencing can be exported.Also, whole process carries out in clean seal cavity, avoids the cross contamination between environmental pollution and sample, improves the quality and efficiency of preparation gene sequencing sample.
[0036]
[0037] Detailed description of the invention
[0038] Fig. 1 is the overall appearance structural representation that the system of gene sequencing sample is used to prepare in the embodiment of the present application；[0039] Fig. 2 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, beats the schematic diagram of internal structure that Jian perspective safety door is seen；
[0040] Fig. 3 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, beats the schematic diagram of internal structure that Jian perspective another visual angle of safety door is seen；
[0041] Fig. 4 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, structure schematic diagram；[0042] Fig. 5 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the schematic diagram of internal structure after removing shell；
[0043] Fig. 6 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the schematic diagram of internal structure after removing shell and frame；
[0044] Fig. 7 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the surface structure schematic diagram of heating and cooling module；
[0045] Fig. 8 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the schematic diagram of internal structure of heating and cooling module；
[0046] Fig. 9 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the surface structure schematic diagram of magnetic beads for purifying module；
[0047] Figure 10 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the decomposition texture schematic diagram of magnetic beads for purifying module；
[0048] Figure 11 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, and suction nozzle placement module assembles the structural schematic diagram of suction nozzle；
[0049] Figure 12 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, and the assembly of suction nozzle placement module is inhaled
The decomposition texture schematic diagram of head；
[0050] Figure 13 is the system that gene sequencing sample is used to prepare in the embodiment of the present application, the structural schematic diagram of nucleic acid amplification module.
[0051]
[0052] specific embodiment
[0053] system for being used to prepare gene sequencing sample of the application, its key be by gene sequencing sample preparation procedure each process and equipment be integrated into a system, whole system carries out in the cavity of an opposing seal, and ensures that entire seal cavity is clean.The system for being used to prepare gene sequencing sample of the application, is controlled by control module, and the automation control of modules may be implemented.
[0054]
[0055] the application is described in further detail below by specific embodiments and the drawings.Following embodiment is only further described the application, should not be construed as the limitation to the application.
[0056]
[0057] embodiment
[0058] system for being used to prepare gene sequencing sample of this example, as shown in Figures 1 to 6, the seal cavity surrounded including one by shell 1, and be arranged in the intracorporal raw material placement module 2 of seal chamber, nucleic acid amplification module 3, heating and cooling module 4, liquid relief module, magnetic beads for purifying module 6, waste recovery module, ultraviolet sterilization lamp 9, code reader 10 and control module.As shown in Figure 1, the top Jian of shell 1 is equipped with air inlet 11, and, as shown in Figure 5, in being equipped with air filter unit 12 in air inlet 11, to ensure that the intracorporal air of seal chamber is clean, the air of Xi Bu circle is entered by air inlet 11, and internal system is then entered after 12 filtration, purification of air filter unit.As shown in Figures 2 and 3, be equipped with before shell 1 one can the perspective safety door 13 that closes of Jian, two side Jian of shell 1 are equipped with see-through window 14;Also, it has an X-rayed safety door 13 and see-through window 14 all to prepare using dark brown transparent material.Wherein, perspective safety door 13 can push and pull up and down, and perspective safety door 13, which beats Jian inch, to operate internal system, such as add raw material or take out the gene sequencing sample prepared, and system operation inch then closes this door.Dark brown transparent material preparation perspective safety door 13 and see-through window 14, both can be convenient environment in testing crew observing system, and the ultraviolet light of ultraviolet sterilization lamp 9 in system can also have been prevented to external radiation with inch.As shown in figure 4, the back side of shell 1, which is additionally provided with USB adapter 15, serial ports control interface 16, power supply Jian, closes 17, network interface 18 and thermovent 19;The power supply Jian that power supply Jian closes 17 control whole systems is opened or is closed
；USB adapter 15 and serial ports control interface 16 are for connecting controlling terminal, including computer or other human-computer interaction interfaces；Network interface 18 is used for system and network connection.Raw material placement module 2 is set in seal cavity, also, raw material placement module 2 includes at least one raw material porous plate 21, can place different samples in each raw material porous plate.
[0059] the liquid relief module of this example is as shown in Figure 5 and Figure 6, including automatic liquid-transfering gun 51, mechanical arm 52 and two suction nozzle placement modules 53,54.Two suction nozzle placement modules 53,54 are for placing suction nozzle；Mechanical arm 52 controls automatic liquid-transfering gun 51 and arbitrarily moves on three directions in X-axis, y-axis and z-axis；Automatic liquid-transfering gun 51 is for drawing and transfer liquid sample.As shown in fig. 6, raw material placement module 2, nucleic acid amplification module 3, heating and cooling module 4, magnetic beads for purifying module 6 and waste recovery module, the X-axis along mechanical arm 52 is sequentially arranged.The raw material of this example are blood plasma, and this example chinese raw materials placement module 2 is mainly used for placing liquid starting material, as solid raw material such as tissues, then can be just put into the system of the application after needing to be smashed homogenate.Two suction nozzle placement modules 53,54 of this example all placed suction nozzle porous plate 531 respectively, a suction nozzle 511 can be placed in each hole as is illustrated by figs. 11 and 12 in two suction nozzle placement modules 53,54.
[0060] heating and cooling module 4 of this example, as shown in Figure 7 and Figure 8, including electric heating assembly, with the alternating temperature porous plate 41 being set on electric heating assembly, room temperature porous plate 42, and it is set to the exhaust fan 43 and radiating subassembly 44 of 42 lower section of alternating temperature porous plate 41 and room temperature porous plate, electric heating assembly is independent to be heated to alternating temperature porous plate 41 and room temperature porous plate 42, alternating temperature porous plate 41 and room temperature porous plate 42 are for placing different sample and reagent, alternating temperature porous plate 41 and room temperature porous plate 42 rely primarily on electric heating assembly and provide heat, exhaust fan 43 and radiating subassembly 44 are used to drain alternating temperature porous plate 41 and the extra heat of room temperature porous plate 42, so that becoming Warm porous plate 41 and room temperature porous plate 42 can rapidly change temperature.Wherein, a constant temperature is kept as room temperature porous plate 42-, in order to quickly control temperature, alternating temperature porous plate 41 and room temperature porous plate 42 are metal material, and this example specifically uses aluminium.
[0061] the nucleic acid amplification module 3 of this example, as shown in figure 13, including heating sealing cover 31, PCR porous plate 32, radiator 33 and exhaust fan 34, PCR porous plate 32 is placed on radiator 33, PCR porous plate 32 is covered tightly sealing in progress P CR reaction inch by heating sealing cover 31, and is heated；PCR porous plate 32 is used for placing response liquid, and heating sealing cover 31 can provide heat for PCR porous plate 32, controls its temperature, radiator 33 and exhaust fan 34 for cooperating the whole control reaction temperature of heating sealing cover 31.Wherein, radiator 33 is used to drain the heat of PCR porous plate, and radiator is equipped with multiple radiating fins 331, and radiating fin one end is equipped with exhaust fan 34, uses
In draining the hot gas in fin.Carrying out PCR amplification inch, heating sealing cover 31 is protruding and is covered on PCR porous plate 32, heating sealing cover can be sealed with device to hole, avoid the evaporation of sample or reagent in hole, same inch, suitable temperature can be provided for PCR reaction with the sample or the accurate heating refrigeration of reagent progress in device to hole
[0062] the magnetic beads for purifying module 6 of this example, as shown in Figure 9 and Figure 10, including purifying porous plate 61, bracket 62, magnetic frame 63 and elevating mechanism 64, purifying porous plate 61 is placed on bracket 62, the independent underface for being set to purifying porous plate 61 of magnetic frame 63, also, elevating mechanism 64 controls magnetic frame 63 and independently rises or falls.Wherein, magnetic frame 63 is equipped with lifting structure 64, about 63 magnetic frame can be driven to fast move for providing magnetic field, magnetic frame 63.Bracket 62 is mainly used for support purifying porous plate 61, and purifying porous plate is provided with magnetic bead solution.It should be noted that, magnetic frame 63 and bracket 62 are not integrated, but separation, in this way, when lifting structure 64 drives magnetic frame 63 to move up and down inch, bracket 62-directly supports purifying porous plate 61 and remains stationary, when needing to mix magnetic bead inch, magnetic frame 63 declines, and by suction nozzle, repeatedly absorption/release purifies the reaction solution in porous plate 61, achievees the purpose that mixing；When needing to retain magnetic bead, liquid inch is removed, magnetic frame 63 rises, and magnetic bead can be adsorbed onto purifying 61 bottom of porous plate, and suction nozzle can be used and siphon away liquid, retain magnetic bead, plays the effect of cleaning purifying magnetic bead surfaces.
[0063] the waste recovery module of this example is a waste recovery box 71.Control module is connect with nucleic acid amplification module 3, heating and cooling module 4, liquid relief module by signal respectively, and independent control nucleic acid amplification module 3, heating and cooling module 4 or mechanical arm 52 are run.Ultraviolet sterilization lamp 9 is installed in the seal cavity that shell 1 surrounds, for carrying out ultraviolet sterilization disinfection to seal cavity.Code reader 10 is installed in the seal cavity surrounded by shell 1, in this example, reagent and various samples all post bar code or two dimensional code on its container, it can be identified by the scanning of code reader 10, record corresponding sample and reagent information, be used for sample tracing management.Conventional power module and control module are provided in the system of this example, these can be not specifically limited herein with reference to conventional power supply and control module, also not specifically illustrated in figure.
[0064] any operation sequence can be set as needed by control module automation control in the system of the preparation gene sequencing sample of this example, and use scope is wide, it can be achieved that operating multiple and different samples with inch.The system of the preparation gene sequencing sample of this example, one of specifically used method are as follows:
[0065] 1. system in a state of nature, can be opened ultraviolet sterilization lamp and air filter unit with Jian and carried out sterilization to the seal cavity of system using preceding；
[0066] 2. dozen of Jian has an X-rayed safety door, various porous plates, reagent and sample are put into corresponding module, first identify at code reader encodes before being put into these reagents and sample, and the Message Entry System of reagent and sample identifies convenient for system automation；
[0067] 3. in the present embodiment, and raw material porous plate is placed in raw material placement module, different plasma samples is placed in the hole of raw material porous plate；PCR porous plate can be previously charged into various reagents, can not also be packed into reagent；The various required reagent solutions of prepackage in alternating temperature porous plate and room temperature porous plate；Suction nozzle porous plate is placed with multiple clean suction nozzles；Purifying porous plate is previously charged into various required reagent solutions；
[0068] 4. closes perspective safety door, and inputs to system and execute program, activation system running；
Automatic liquid-transfering gun is moved to above suction nozzle porous plate by [0069] 5. mechanical arm, and automatic liquid-transfering gun moves down and by suction nozzle needed for pressure handling, is pressed by pressure and is guaranteed the success of handling suction nozzle and its leakproofness, is then lifted up suction nozzle again；
[0070] 6. mechanical arm moves to suction nozzle above room temperature porous plate or purifying porous plate, and reagent is drawn to suction nozzle, and then suction nozzle is moved to alternating temperature porous plate again by mechanical arm, and liquid in suction nozzle is discharged into alternating temperature porous plate；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；
[0071] 7. automatic liquid-transfering gun loads new suction nozzle, and then suction nozzle is moved to raw material porous plate and draws plasma sample by mechanical arm；
Suction nozzle is moved to alternating temperature porous plate by [0072] 8. mechanical arm, liquid in suction nozzle is discharged into alternating temperature porous plate, system can these steps repeatedly, plasma sample and various reagents are mixed, in this process, the operation that heating and cooling module constantly can be heated or be freezed to alternating temperature porous plate provides suitable temperature for chemical reaction；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；
[0073] 9. automatic liquid-transfering gun loads new suction nozzle, and the liquid in alternating temperature porous plate is moved to purifying porous plate, and magnetic frame rises, and magnetic bead is adsorbed on purifying multi-well plate bottom, automatic liquid-transfering gun siphons away waste liquid；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；Magnetic frame decline, can use suction nozzle and cleaning solution is added into the hole for have magnetic bead, then draw/discharge magnetic bead solution repeatedly, play
The effect of magnetic bead is cleaned, then magnetic frame rises, and siphons away waste liquid, and then magnetic frame decline rejoins new reagent, repeatedly this step, then can play the role of cleaning magnetic bead repeatedly；Last magnetic frame rises, and magnetic bead is adsorbed on purifying multi-well plate bottom, automatic liquid-transfering gun siphons away waste liquid；Remaining magnetic bead；
The decline of [0074] 10. magnetic frame, automatic liquid-transfering gun move to purifying porous plate and draw reagent, reagent is discharged into the hole location of magnetic bead, draws/discharge magnetic bead solution repeatedly, the DNA adsorbed on magnetic bead is eluted；Then magnetic frame rises, and magnetic bead is adsorbed on to the bottom in hole, thus obtains the solution of DNA molecular, these operations can finally extract DNA molecular from blood plasma；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；
[0075] 11. automatic liquid-transfering gun moves to the DNA solution that purifying porous plate is drawn, DNA solution after extraction is moved in PCR porous plate, then it moves to room temperature porous plate and draws enzyme reaction solution, automatic liquid-transfering gun moves to PCR porous plate, the enzyme reaction solution in suction nozzle is discharged, then DNA solution is reacted in PCR porous plate；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；
[0076] 12. completes the DNA solution of enzyme reaction, it needs to carry out purification process: being mixed into magnetic bead solution to DNA molecular solution, sufficiently after reaction, DNA molecular is adsorbed on magnetic bead, then after automatic liquid-transfering gun exchanges new suction nozzle for, which is transferred in purifying porous plate；Mechanical arm again moves to suction nozzle above suction nozzle porous plate, and suction nozzle is discharged into hole in case following cycle utilization can directly abandon suction nozzle release to waste recovery box if subsequent do not need to reuse these suction nozzles；The step of purifying magnetic bead can refer to step 9,10；
[0077] 13. carries out pure DNA solution taking-up to reinject PCR porous plate after manually quantifying, the heating sealing cover of this inch nucleic acid amplification module is protruding and is closed together on PCR porous plate, heating sealing cover can carry out alternating temperature operation, provide suitable reaction environment for DNA cloning；
It can manually be taken out after [0078] 14. DNA cloning, carry out quantitative Treatment, then put back to again and carry out subsequent processing in system, various required reagents are added, carry out various reactions, the DNA nanosphere solution of concentration needed for being formed；
It is manually drawn off after the DNA nanosphere solution of concentration needed for [0079] 15. formation, carries out quantitative preservation, ultimately form the sample that can carry out gene sequencing.
[0080] it should be noted that above step is only one of operating process of this system, different operating processes can be arranged in experimenter according to the specific requirements of test.
[0081] it can be seen that the system of this example, which one-stop can automatically complete DNA extraction, enzyme reaction and purifying etc., builds library operation, final to obtain gene sequencing sample, what this example specifically obtained is DNA nanosphere library.The sequenator that the system of this example can be researched and developed with Hua Da gene matches, and provides gene sequencing sample for it.
[0082] the raw material porous plate of this example can place 16 test samples, and automatic liquid-transfering gun can load 8 suction nozzles with inch, it is, of course, also possible to be designed to requirement as needed.
[0083]
[0084] the foregoing is a further detailed description of the present application in conjunction with specific implementation manners, and it cannot be said that the specific implementation of the application is only limited to these instructions.For those of ordinary skill in the art to which this application belongs, without departing from the concept of this application, a number of simple deductions or replacements can also be made, all shall be regarded as belonging to the protection scope of the application.
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/CN2016/099816 WO2018053783A1 (en) | 2016-09-23 | 2016-09-23 | System for preparing gene sequencing samples and application thereof |
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| CN109580974A (en) * | 2018-12-31 | 2019-04-05 | 华测检测认证集团股份有限公司 | The multichannel of Rapid replacement automates titration outfit |
| CN109652288A (en) * | 2019-02-25 | 2019-04-19 | 成都瀚辰光翼科技有限责任公司 | A kind of automation Genotyping device and method |
| CN112175943A (en) * | 2020-10-29 | 2021-01-05 | 绍兴迅敏康生物科技有限公司 | Continuous sample introduction sequencing library building instrument and operation method thereof |
| CN112625888A (en) * | 2020-12-10 | 2021-04-09 | 武汉华大智造科技有限公司 | Sequencing reaction device |
| CN113173399A (en) * | 2021-03-15 | 2021-07-27 | 北京戴纳实验科技有限公司 | Transport case nucleic acid detecting system |
| CN113759136A (en) * | 2021-09-09 | 2021-12-07 | 珠海圣美生物诊断技术有限公司 | Full-automatic sample slide treatment instrument and sample slide treatment method |
| CN114369525A (en) * | 2020-10-19 | 2022-04-19 | 成都瀚辰光翼生物工程有限公司 | Gene detecting apparatus |
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| CN114134032B (en) * | 2021-12-02 | 2022-08-05 | 杭州奥盛仪器有限公司 | Gene sequencing pretreatment device |
| WO2023144686A1 (en) * | 2022-01-28 | 2023-08-03 | Mylab Discovery Solutions Private Limited | A deck assembly for a diagnostic system |
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Application publication date: 20180928 |