CN110904206A - Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system - Google Patents
Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system Download PDFInfo
- Publication number
- CN110904206A CN110904206A CN201911309913.0A CN201911309913A CN110904206A CN 110904206 A CN110904206 A CN 110904206A CN 201911309913 A CN201911309913 A CN 201911309913A CN 110904206 A CN110904206 A CN 110904206A
- Authority
- CN
- China
- Prior art keywords
- reaction
- way valve
- reagent
- pump
- reaction device
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 34
- 238000004458 analytical method Methods 0.000 title claims abstract description 27
- 150000007523 nucleic acids Chemical group 0.000 title claims description 35
- 108091028043 Nucleic acid sequence Proteins 0.000 title claims description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 313
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 181
- 239000012530 fluid Substances 0.000 claims description 32
- 238000012163 sequencing technique Methods 0.000 claims description 28
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- 238000004891 communication Methods 0.000 claims description 23
- 238000003776 cleavage reaction Methods 0.000 claims description 12
- 230000007017 scission Effects 0.000 claims description 12
- 239000002699 waste material Substances 0.000 claims description 11
- 230000003252 repetitive effect Effects 0.000 claims description 6
- 238000009396 hybridization Methods 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 125000003729 nucleotide group Chemical group 0.000 description 24
- 239000002773 nucleotide Substances 0.000 description 19
- 239000000523 sample Substances 0.000 description 14
- 238000004140 cleaning Methods 0.000 description 9
- 238000012545 processing Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000007841 sequencing by ligation Methods 0.000 description 3
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- -1 nucleotide glycosides Chemical class 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
Abstract
The application discloses a liquid path system and a biomolecule analysis system. The liquid path system is used for providing a solution environment for analyzing the biomolecules, the first reaction comprises connecting the biomolecules into the reaction device by using a first reagent, and the second reaction comprises detecting the biomolecules connected into the reaction device by using a second reagent. The liquid path system comprises a valve body assembly and a driving assembly. The valve body assembly comprises a first multi-way valve and a second multi-way valve. The driving assembly comprises a first pump and a second pump. Under the condition that the first multi-way valve is communicated with the reaction device and the first pump, and the second multi-way valve is communicated with the reaction device and the first reagent, the first pump is used for driving the first reagent to enter the reaction device along a first direction so as to perform a first reaction; under the condition that the second multi-way valve is communicated with the reaction device and the second pump, and the first multi-way valve is communicated with the reaction device and the second reagent, the second pump is used for driving the second reagent to enter the reaction device along the second direction so as to perform a second reaction.
Description
Technical Field
The present application relates to the field of biomolecule analysis technology, and more particularly, to a fluid path system, a biomolecule analysis system, and a nucleic acid sequence determination system.
Background
In the related art, apparatuses for performing nucleic acid analysis on a nucleic acid sample placed on a solid substrate, such as nucleic acid sequencing (sequencing) based on chip detection, generally involve sample processing before loading a sample to be tested so as to meet the requirements of the loading on a computer, such as connection to a chip, and loading the processed sample into a sequencer for sequencing.
With the development of automated related technologies, related commercially available sequencing platforms often include two or more separate or functionally linked devices, which are typically sold or purchased in sets when a certain sequencing platform is sold or purchased.
For a sequencing platform comprising two associated devices, typically one of the devices for processing a nucleic acid sample to be tested comprises attaching it to a reaction device, such as a chip, the device often being referred to as a hybridization apparatus, a sample introduction apparatus or a sample processing apparatus; the other device detects the chip connected with the nucleic acid sample output by the last device, thereby realizing the determination of the nucleic acid sequence, and the device is the most main hardware of a sequencing platform and is often called a sequencer.
A commercial sequencing platform, which comprises a plurality of automated devices for processing and detecting samples, is at least partly due to the complexity of the fluid control involved in processing samples before computer and in computer sequencing, for example, sample processing before computer often includes a plurality of steps and a plurality of reactions, involving a plurality of reagents and a plurality of fluid inlet and outlet sequences, and some of the reagents or reactions may have special requirements on the material, flow rate, pressure, etc. of the pipeline, and further, sequencing itself generally involves a plurality of reagents and a plurality of reactions; still another part is the susceptibility of biochemical reactions to interference, including the susceptibility of reagents to contamination.
Therefore, the liquid path system for sample processing before the computer and the liquid path system for sequencing are integrated, a set of liquid path system which can realize the processing of the sample before the computer and the sequencing of the processed sample can be constructed, the interference or the pollution can not be caused, and the method is also suitable for industrialization and is very difficult.
Disclosure of Invention
The embodiment of the application provides a liquid path system, a biomolecule analysis system and a nucleic acid sequence measuring system.
The liquid path system of this application embodiment is used for providing solution environment for the analysis biomolecule, the analysis biomolecule includes and carries out first reaction and second reaction on reaction unit, first reaction includes that to utilize first reagent to make the biomolecule be connected to in the reaction unit, the second reaction includes to utilize the second reagent to be connected to biomolecule among the reaction unit detects, the liquid path system includes valve body subassembly and drive assembly, the valve body subassembly includes first multi-way valve and second multi-way valve, first multi-way valve can communicate the second reagent with reaction unit, the second multi-way valve can communicate the first reagent with reaction unit; the driving assembly comprises a first pump and a second pump, the first pump is connected with the first multi-way valve, and the second pump is connected with the second multi-way valve; under the condition that the first multi-way valve is communicated with the reaction device and the first pump, and the second multi-way valve is communicated with the reaction device and the first reagent, the first pump is used for driving the first reagent to enter the reaction device along a first direction so as to perform the first reaction; and under the condition that the second multi-way valve is communicated with the reaction device and the second pump, and the first multi-way valve is communicated with the reaction device and the second reagent, the second pump is used for driving the second reagent to enter the reaction device along a second direction so as to perform the second reaction.
The biological molecules are referred to as biological macromolecules, such as proteins or nucleic acids. In certain embodiments, the biomolecule is a nucleic acid, the first reaction comprises a hybridization reaction, and/or the second reaction comprises a sequencing reaction.
In certain embodiments, the valve body assembly further comprises a third multi-way valve that can communicate the second reagent and the first multi-way valve.
In certain embodiments, the third multi-way valve includes a stator and a rotor that are communicable, the third multi-way valve includes a common port, the stator includes a plurality of ports, the rotor includes a communication groove, and the rotor is rotatable to communicate the common port with at least one of the ports through the communication groove.
In some embodiments, the first multi-way valve includes a plurality of ports, the plurality of ports are connected to at least the second reagent, the reaction device and the first pump, respectively, and any two ports on the first multi-way valve can be communicated.
In some embodiments, the reaction apparatus includes a first unit and a second unit, the first multi-way valve is a four-way valve, and four ports of the four-way valve are respectively connected to the second reagent, the first unit, the second unit, and the first pump.
In some embodiments, the second multi-way valve includes three ports, three of the ports are respectively connected to the first reagent, the reaction device and the second pump, and any two of the ports of the second multi-way valve can be communicated.
In certain embodiments, the second multi-way valve is a three-way valve.
In some embodiments, the reaction device comprises a plurality of channels, the number of the second multi-way valves and the number of the second pumps are not less than the number of the channels, and one second multi-way valve can communicate one channel and one second pump.
In certain embodiments, the fluid path system further comprises a manifold assembly in communication with the first pump, the manifold assembly configured to collect the first reagent after the first reaction; and/or the collecting assembly is communicated with the second pump and is used for collecting the second reagent after the second reaction.
In certain embodiments, the manifold assembly is further configured to collect the second reagent driven by the first pump when the first pump and the second reagent are in communication through the first multi-way valve.
In certain embodiments, the manifold assembly includes a fluid trap including a first port in communication with a plurality of the second ports and a plurality of second ports, a first pump in communication with the second ports, a second pump in communication with the second ports, and a waste bottle in communication with the first ports.
In certain embodiments, after performing the first reaction or before beginning the second reaction, the first multi-way valve can communicate the first pump and the second reagent, and/or communicate the second pump and the second reagent, and the first pump and/or the second pump can be used to drive the second reagent to fill the flow path of the first multi-way valve with the second reagent.
In certain embodiments, the first direction is opposite the second direction.
The biomolecule analysis system of the embodiments of the present application includes the liquid path system of any of the embodiments of the present application.
In certain embodiments, the biomolecule analysis system further includes a reaction device connecting the first and second multi-way valves.
In some embodiments, the biomolecule is a nucleic acid, the reaction device includes a first unit and a second unit, the biomolecule analysis system further includes a signal acquisition device for acquiring a signal; the second reaction is a nucleic acid sequencing reaction comprising a plurality of repetitive reactions, one of the repetitive reactions comprising a base extension reaction, signal acquisition, and radical cleavage; and (b) performing the base extension reaction and/or the radical cleavage in one of the first unit and the second unit by using the liquid path system, and simultaneously performing the signal acquisition in the other of the first unit and the second unit by using the signal acquisition device. Thus, the efficiency of measuring the nucleic acid molecule can be improved.
The nucleic acid sequencing system of the embodiments of the present application includes the fluid path system of any of the embodiments of the present application.
In certain embodiments, the nucleic acid sequence determination system further comprises a reaction device connecting the first multi-way valve and the second multi-way valve.
In the fluid path system, biomolecule analytic system and nucleic acid sequence measurement system of any embodiment of this application, through switching first multi-way valve intercommunication reaction unit and first pump, and switch second multi-way valve intercommunication reaction unit and first reagent, can carry out first reaction in the reaction unit, through switching second multi-way valve intercommunication reaction unit and second pump, and switch first multi-way valve intercommunication reaction unit and second reagent, can carry out the second reaction in the reaction unit, can realize carrying out first reaction and second reaction on the reaction unit through a fluid path system, the structure of the fluid path system of realization first reaction and second reaction is simpler, and, the cost of setting up this integrated fluid path system is far less than the sum of the cost of setting up the fluid path system of realizing first reaction alone and the fluid path system of realizing the second reaction alone.
Additional aspects and advantages of embodiments of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of embodiments of the present application.
Drawings
The above and/or additional aspects and advantages of the present application will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a block diagram of a biomolecule analysis system in one state according to an embodiment of the present application;
FIG. 2 is a schematic block diagram of a biomolecule analysis system in another state according to an embodiment of the present application;
FIG. 3 is a schematic illustration of the third and first multi-way valves of an embodiment of the present application;
fig. 4 is a block diagram of a biomolecule analysis system according to an embodiment of the present application in still another state.
Description of the main element symbols:
the system comprises a biomolecule analysis system 1000, a liquid path system 100, a valve body assembly 10, a first multi-way valve 11, ports 111, 112, 113, 114, a second multi-way valve 12, ports 121, 122, 123, a third multi-way valve 13, a stator 131, a rotor 132, a common port 133, a port 134, a communication groove 135, a driving assembly 20, a first pump 21, a second pump 22, a flow collecting assembly 30, a liquid collecting piece 31, a second port 311, a first port 312, a waste liquid bottle 32, a reaction device 200, a first unit 201, a second unit 202, a channel 203, a second reagent 300 and a first reagent 400.
Detailed Description
Embodiments of the present application will be further described below with reference to the accompanying drawings. The same or similar reference numbers in the drawings identify the same or similar elements or elements having the same or similar functionality throughout.
In addition, the embodiments of the present application described below in conjunction with the accompanying drawings are exemplary and are only for the purpose of explaining the embodiments of the present application, and are not to be construed as limiting the present application.
In this application, unless expressly stated or limited otherwise, the first feature "on" or "under" the second feature may be directly contacting the first and second features or indirectly contacting the first and second features through intervening media. Also, a first feature "on," "over," and "above" a second feature may be directly or diagonally above the second feature, or may simply indicate that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the first feature, or may simply mean that the first feature is at a lesser elevation than the second feature.
Referring to fig. 1, the present embodiment provides a biomolecule analysis system 1000, and the biomolecule analysis system 1000 includes a fluid path system 100 and a detachable reaction device 200 connected to the fluid path system 100. The biomolecule analysis system 1000 may be specifically a nucleic acid sequence determination system, and the fluid path system 100 is used to provide a solution environment for analyzing biomolecules including performing a first reaction and a second reaction in the reaction device 200. Wherein the first reaction includes coupling the biomolecule into the reaction device 200 using the first reagent 400, and the second reaction includes detecting the biomolecule coupled into the reaction device 200 using the second reagent 300.
The fluid circuit system 100 includes a valve body assembly 10 and a drive assembly 20. The valve body assembly 10 includes a first multi-way valve 11 and a second multi-way valve 12. The first multi-way valve 11 may communicate the second reagent 300 with the reaction device 200, and the second multi-way valve 12 may communicate the first reagent 400 with the reaction device 200. The driving assembly 20 includes a first pump 21 and a second pump 22, the first pump 21 is connected to the first multi-way valve 11, and the second pump 22 is connected to the second multi-way valve 12. The reaction device 200 is connected between the first and second multi-way valves 11 and 12.
In a state where the first multi-way valve 11 communicates with the reaction device 200 and the first pump 21, and the second multi-way valve 12 communicates with the reaction device 200 and the first reagent 400, the first pump 21 is used to drive the first reagent 400 to enter the reaction device 200 in the first direction to perform the first reaction. Under the condition that the second multi-way valve 12 communicates with the reaction device 200 and the second pump 22, and the first multi-way valve 11 communicates with the reaction device 200 and the second reagent 300, the second pump 22 is used for driving the second reagent 300 to enter the reaction device 200 along the second direction to perform the second reaction.
In the biomolecule analysis system 1000 according to the embodiment of the present application, the reaction apparatus 200 and the first pump 21 are communicated by switching the first multi-way valve 11, and the reaction apparatus 200 and the first reagent 400 are communicated by switching the second multi-way valve 12, a first reaction may be carried out in the reaction apparatus 200 by switching the second multi-way valve 12 to communicate the reaction apparatus 200 with the second pump 22, and switching the first multi-way valve 11 to communicate the reaction apparatus 200 with the second reagent 300, the second reaction can be carried out in the reaction device 200, the first reaction and the second reaction can be carried out in the reaction device 200 through one liquid path system 100, the structure of the liquid path system 100 for realizing the first reaction and the second reaction is simpler, the first reaction and the second reaction do not need to be carried out in different systems separately, the operation of a user is simpler and more convenient, moreover, the cost of building this integrated fluid circuit system 100 is much lower than the sum of the costs of building a fluid circuit system that implements the first reaction alone and a fluid circuit system that implements the second reaction alone.
Specifically, referring to fig. 1 and 2, fig. 1 is a schematic block diagram illustrating a first reaction performed on a reaction apparatus 200, and fig. 2 is a schematic block diagram illustrating a second reaction performed on the reaction apparatus 200. The first reaction of the present embodiment includes a reaction of attaching a biomolecule into the reaction device 200, or is referred to as a hybridization reaction. The term biomolecule includes DNA and/or RNA and the like, including ribonucleotides, deoxyribonucleotides and analogs thereof, including A, T, C, G and U and analogs thereof. Wherein C represents cytosine or a cytosine analogue, G represents guanine or a guanine analogue, A represents adenine or an adenine analogue, T represents thymine or a thymine analogue, and U represents uracil or a uracil analogue. The reaction apparatus 200 may be a reaction site including a substrate, and the reaction apparatus 200 may be in the form of a chip, and the reaction apparatus 200 may be detachably connected to the liquid path system 100. The substrate can be any solid support useful for immobilizing nucleic acid sequences, such as nylon membranes, glass sheets, plastics, silicon wafers, magnetic beads, and the like. Probes can be randomly distributed on the surface of the substrate, can be a section of DNA and/or RNA sequence and the like, and can also be called as a primer, a capture chain or a fixed chain. The first reaction may fixedly attach the biomolecule to the probe, for example, based on the base complementary principle, so that the biomolecule is attached to the reaction device 200. The first reagent 400 may include a solution for performing a first reaction, for example, a hybridization solution including the above-described biomolecules.
The second reaction includes a reaction for detecting a biomolecule, for example, a nucleic acid, attached to the reaction device 200, and the second reaction may be a sequencing reaction, so-called sequencing, including determining the primary structure or sequence of DNA or RNA, etc., including determining the order of nucleotides/bases of a given nucleic acid fragment. The second reaction may comprise one or more sub-reactions, in one example, sequencing the DNA, the second reaction being sequencing, based on sequencing by synthesis or sequencing by ligation, the sequencing comprising a plurality of sub-reactions including base extension reaction, signal acquisition and radical excision; performing the plurality of sub-reactions once may be referred to as performing one repeat reaction or one round of reaction, and sequencing comprises performing a plurality of repeat reactions or multiple rounds of reactions to determine the nucleotide/base order of at least one sequence of the nucleic acid molecule (template).
Wherein the base extension reaction comprises binding nucleotide glycosides (including modified nucleotides) to nucleic acid molecules by polymerase or ligase based on the base complementary principle for Sequencing By Synthesis (SBS) or Sequencing By Ligation (SBL) on the reaction apparatus 200 on which the nucleic acid molecules are immobilized, and collecting corresponding reaction signals. For example, an engineered nucleotide may refer to a nucleotide with a label that allows the engineered nucleotide to be detected under certain circumstances, e.g., a nucleotide with a fluorescent molecular label that fluoresces when excited by a laser of a particular wavelength; in general, for SBS, an engineered nucleotide typically also has the function of inhibiting the binding of another nucleotide to the next position of the same nucleic acid molecule, e.g., with a blocking group that prevents the binding of other nucleotides to the next position of the template, e.g., a blocking group such as an azide (-N) group attached at the 3' position of the sugar moiety of the nucleotide3)。
The second reagent 300 comprises a polymerase and an engineered nucleotide, and in one example, the second reagents 300 are each loaded in five separate containers, each of which is loaded with a polymerase and four engineered nucleotides, the polymerase and one or more nucleotides are mixed in the reaction apparatus 200, and the controlled polymerase chain reaction is performed under suitable conditions, i.e., the base extension reaction is achieved. In another example, the second reagent 300 further includes other solutions, such as imaging reagents, washing reagents, etc., that are independently supported.
Collecting the signal includes collecting the signal emitted from the modified nucleotide bound to the nucleic acid molecule, for example, by irradiating a specific region of the reaction apparatus 200 after the base extension reaction, in which the nucleotide labeled with the fluorescent molecule fluoresces, optionally, the second reagent 300 further includes an information collecting reagent such as an imaging reagent, for example, an antioxidant, to facilitate collection of the fluorescent signal, and the information collecting reagent can be carried independently in a container, and such second reagent 300 (hereinafter also referred to as the information collecting reagent) can be added to the reaction apparatus 200 to facilitate collection of information about the modified nucleotide, for example, to facilitate acquisition of the light emitted from the modified nucleotide or the fluorescent molecule thereon by the imaging apparatus into an image.
Group excision involves removal of the detectable label and/or blocking group bound to the engineered nucleotide of the nucleic acid molecule after the base extension reaction to enable the binding of other nucleotides (including engineered nucleotides) to the next position of the nucleic acid molecule for the next repeat reaction or round of reaction. In one example, the second reagent 300 further comprises a cleavage reagent separately carried in a container that is passed to simultaneously remove the detectable label and blocking group on the engineered nucleotide upon the performance of the radical cleavage sub-reaction.
The second reagent 300 introduced into the reaction apparatus 200 may be different depending on the different sub-reactions being performed, for example, the second reagent 300 including the modified nucleotide may be introduced when the base extension reaction is performed, the second reagent 300 (i.e., one of the information collecting reagents) advantageous for performing imaging may be introduced when the signal collection is performed, and the second reagent 300 for removing the detectable label and the blocking group on the modified nucleotide (hereinafter referred to as a cleavage reagent) may be introduced when the group cleavage is performed. Further, after the completion of the previous sub-reaction and before the start of the next sub-reaction, a washing reagent may be introduced to remove unreacted substances remaining in the reaction apparatus 200 or in the channel system 100, substances interfering with the reaction or signal collection, the washing reagent may be one of the second reagents 300, and the washing reagent may be a buffer solution not interfering with the base extension reaction.
Unless otherwise specified, the second reaction described below is sequencing, including any one or more of the sub-reactions of the second reaction described above, and a washing procedure between the two sub-reactions.
With continued reference to fig. 1 and 2, the reaction apparatus 200 can provide reaction sites for the first reaction and the second reaction. Specifically, the reaction device 200 may include one or more channels 203, and the first reagent 400 may enter the channel 203 or flow through the channel 203 in a first direction (e.g., a first direction X shown in fig. 1) when performing the first reaction, and the second reagent 300 may enter the channel 203 or flow through the channel 203 in a second direction (e.g., a second direction Y shown in fig. 1, which may be opposite to the first direction X) when performing the second reaction.
In the embodiment of the present application, the reaction apparatus 200 includes a first unit 201 and a second unit 202. The first unit 201 comprises one or more channels 203 and the second unit 202 comprises one or more channels 203. The same reaction may be performed in the first cell 201 and the second cell 202, or different reactions may be performed in the first cell and the second cell. For example, when the first reaction is performed in the first unit 201, the first reaction or the second reaction may be performed in the second unit 202, or no reaction may be performed in the second unit 202; when the second reaction is performed in the first unit 201, the first reaction or the second reaction may be performed in the second unit 202, or no reaction may be performed in the second unit 202; when a sub-reaction (e.g., base extension) of the second reaction is performed in the first unit 201, another sub-reaction (e.g., signal acquisition) of the second reaction may be performed in the second unit 202, which is not limited herein.
In the example shown in fig. 1 and 2, the first unit 201 includes a plurality of channels 203. One end of the plurality of channels 203 of the first unit 201 adjacent to the first multi-way valve 11 may be commonly connected to one port 112 of the first multi-way valve 11. One end of each channel 203 of the first unit 201 close to the second multi-way valve 12 can be connected with one port 121 of one second multi-way valve 12, so that different first reagents 400 can be introduced into different channels 203 during the first reaction, different biomolecules can be connected into different channels 203, and the different first reagents 400 cannot be cross-contaminated before the first reaction. The arrangement of the channels 203 in the second unit 202 may be the same as the arrangement of the channels 203 in the first unit 201, and will not be described herein again.
With continued reference to fig. 1 and 2, the first multi-way valve 11 may communicate the first pump 21 with the reaction device 200, the first multi-way valve 11 may further communicate the second reagent 300 with the reaction device 200, and the first multi-way valve 11 may further communicate the second reagent 300 with the first pump 21. Specifically, the first multi-way valve 11 includes a plurality of ports 111, 112, 113, and 114, the plurality of ports 111, 112, 113, and 114 are connected to at least the second reagent 300, the reaction device 200, and the first pump 21, respectively, and any two of the plurality of ports 111, 112, 113, and 114 can communicate with the first multi-way valve 11. The first multi-way valve 11 may be a four-way valve, a five-way valve, a six-way valve, etc., and is not limited herein. When the reaction apparatus 200 includes only one of the first unit 201 and the second unit 202, the first multi-way valve 11 may also be a three-way valve. In the example shown in fig. 1 and 2, the port 111 is connected to the second reagent 300, the port 112 is connected to the first unit 201, the port 113 is connected to the second unit 202, and the port 114 is connected to the first pump 21.
The first multi-way valve 11 may communicate with any two of the plurality of ports 111, 112, 113, 114 to communicate a flow passage between any two of the ports 111, 112, 113, 114. The port 112 may be made to communicate with the port 114, for example, by switching the state of the first multi-way valve 11, to communicate the first pump 21 with the first unit 201; the port 113 may be made to communicate with the port 114 to communicate the first pump 21 with the second unit 202; port 111 may be brought into communication with port 112 to communicate the second reagent 300 with the first cell 201; port 111 may be put in communication with port connection 113 to communicate the second reagent 300 with the second cell 202; port 111 may be brought into communication with port 114 to communicate the second reagent 300 with the first pump 21.
With continued reference to fig. 1 and 2, the second multi-way valve 12 may communicate the first reagent 400 with the reaction apparatus 200, the second multi-way valve 12 may communicate the second pump 22 with the reaction apparatus 200, and the second multi-way valve 12 may further communicate the first reagent 400 with the second pump 22. Specifically, the second multi-way valve 12 includes three ports 121, 122, 123, the three ports 121, 122, 123 are respectively connected to the reaction device 200, the first reagent 400, and the second pump 22, and the second multi-way valve 12 can communicate any two of the three ports 121, 122, 123. The second multi-way valve 12 may be a three-way valve, a four-way valve, a five-way valve, etc., and is not limited herein.
The second multi-way valve 12 may communicate any two of the three ports 121, 122, 123 to communicate the flow passages to which any two ports 121, 122, 123 are connected. For example, by switching the state of the second multi-way valve 12, the port 121 can be made to communicate with the port 122 to communicate the first reagent 400 with the reaction device 200; the port 121 and the port 123 may be made to communicate the second pump 22 with the reaction device 200 (the first unit 201 or the second unit 202); by switching the state of the second multi-way valve 12, the port 122 may be brought into communication with the port 123 to communicate the first reagent 400 with the second pump 22.
When the number of the passages 203 is plural, the number of the second multi-way valves 12 may also be plural, the number of the second multi-way valves 12 is not less than the number of the passages 203, and one second multi-way valve 12 communicates with one passage 203. At this time, the communication states of the plurality of second multi-way valves 12 may not be affected, for example, a part of the second multi-way valves 12 may communicate the first reagent 400 with the reaction apparatus 200, and another part of the second multi-way valves 12 may communicate the second pump 22 with the reaction apparatus 200, so that different channels 203 of the reaction apparatus 200 may perform different reactions.
With continued reference to fig. 1 and 2, the first pump 21 is connected to the first multi-way valve 11. When the first multi-way valve 11 communicates the first pump 21 with the second reagent 300, the first pump 21 may be used to drive the second reagent 300 into the first pump 21; when the first multi-way valve 11 communicates the first pump 21 with the reaction device 200, the first pump 21 can be used to drive the reagent in the reaction device 200 into the first pump 21. The second pump 22 is connected to the second multi-way valve 12. When the second multi-way valve 12 communicates the first reagent 400 with the second pump 22, the second pump 22 may be used to drive the first reagent 400 into the second pump 22; when the second multi-way valve 12 communicates the reaction device 200 with the second pump 22, the second pump 22 may be used to drive the reagent in the reaction device 200 into the second pump 22. The number of the second pumps 22 may be plural, and the number of the second pumps 22 may be the same as the number of the second multi-way valves 12, and each of the second pumps 22 is connected to one of the second multi-way valves 12.
In one example, the first multi-way valve 11 can be directly connected to the second reagent 300, and in another example, the first multi-way valve 11 can be indirectly connected to the second reagent 300, for example, a valve body can be disposed between the first multi-way valve 11 and the second reagent 300. Referring to fig. 3, in the embodiment of the present application, the valve body assembly 10 further includes a third multi-way valve 13. The third multi-way valve 13 may communicate the second reagent 300 with the first multi-way valve 11. The third multi-way valve 13 may in particular be a rotary valve.
Specifically, the third multi-way valve 13 includes a stator 131 and a rotor 132 that are communicable, the third multi-way valve 13 includes a common port 133, and the stator 131 includes a plurality of ports 134. The rotor 132 includes a communication groove 135, and the rotor 132 is rotatable to communicate the common port 133 with at least one port 134 through the communication groove 135.
The common port 133 may be connected to the first multi-way valve 11, and in particular, may be connected to the port 111 of the first multi-way valve 11. The number of ports 134 is plural, and may be six, seven, eight, ten, eleven, twelve, thirteen, fourteen, sixteen, etc., and each port 134 may communicate with a different composition of second reagent 300, such as one port 134 communicating with reagent I, another port 134 communicating with reagent II, yet another port 134 communicating with reagent III, etc. The second reagent 300 may be contained in reagent tubes, the second reagents 300 of different compositions may be contained in different reagent tubes, respectively, the number of the ports 134 may be the same as the number of the reagent tubes, and one port 134 may be connected to the second reagent 300 in one reagent tube through a pipe. The common port 133 can be made to communicate with the different ports 134 through the communication groove 135 by rotating the rotor 132 to communicate the first multi-way valve 11 with the second reagent 300 of different composition to meet the demand for the different types of second reagents 300 in the second reaction currently in progress.
Referring to fig. 1 and 2, in some embodiments, the fluid path system 100 further includes a collecting assembly 30, the collecting assembly 30 is in communication with the first pump 21, and the collecting assembly 30 is configured to collect the first reagent 400 after the first reaction. When the first pump 21 and the second reagent 300 are communicated through the first multi-way valve 11, the collecting module 30 may also be used to collect the second reagent 300 driven by the first pump 21, and at this time, the second reagent 300 may not pass through the reaction device 200, and the second reagent 300 enters the collecting module 30 after passing through the first pump 21. Manifold assembly 30 may also be in communication with second pump 22, and manifold assembly 30 is configured to collect second reagent 300 after the second reaction.
Therefore, the collecting assembly 30 can be used for collecting the waste liquid after the first reaction and the second reaction, so that the waste liquid can be conveniently treated in a centralized manner. Specifically, the manifold assembly 30 includes a liquid trap 31 and a waste bottle 32. The liquid trap 31 includes a first port 312 and a plurality of second ports 311, and the first port 312 communicates with the plurality of second ports 311. The first pump 21 communicates with the second port 311, the second pump 22 communicates with the second port 311, and the waste bottle 32 communicates with the first port 312. The first reagent 400 after the first reaction or the second reagent 300 after the second reaction can enter the liquid trap 31 through the second port 311, and the reagent entering the liquid trap 31 flows out of the first port 312 into the waste liquid bottle 32.
The following will illustrate the process of performing the first reaction and the second reaction by taking the biomolecule analysis system 1000 in the example shown in FIGS. 1, 2 and 4 as an example:
as shown in fig. 1, when the first reaction is required, the port 121 of the second multi-way valve 12 communicates with the port 122 to communicate the second multi-way valve 12 with the reaction device 200 and the first reagent 400, and the port 112 or 113 of the first multi-way valve 11 communicates with the port 114 to communicate the first multi-way valve 11 with the reaction device 200 and the first pump 21. The first pump 21 is turned on so that the first pump 21 drives the first reagent 400 into the reaction apparatus 200 along the first direction X to perform the first reaction. Under the driving of the first pump 21, the first reagent 400 can also enter the first pump 21 and further enter the liquid trap 31 and the waste liquid bottle 32. Because the plurality of channels 203 of the reaction apparatus 200 are connected to the plurality of second multi-way valves 12 in a one-to-one correspondence manner, and the plurality of second multi-way valves 12 are connected to the plurality of first reagents 400 in a one-to-one correspondence manner, different first reagents 400 can flow into different channels 203, different biomolecules can be connected to different channels 203, and cross contamination is not generated when different channels 203 perform the first reaction. In addition, the first reagent 400 enters the reaction device 200 along the first direction X, and before the first reagent 400 enters the reaction device 200 for the first reaction, the first reagent does not need to pass through the pipelines such as the first multi-way valve 11 and the third multi-way valve 13, so that the wall hanging of the first reagent 400 on the pipelines is reduced, the liquid passing of the micro first reagent 400 can be realized, the loss of the first reagent 400 is reduced, and the cost is saved.
As shown in fig. 2 and 3, after the first reaction is completed, the liquid path system 100 may be cleaned using the cleaning reagent in the second reagent 300. Specifically, by rotating the rotor 132 of the third multi-way valve 13, the port 134 of the third multi-way valve 13, which communicates with the cleaning reagent, is made to communicate with the common port 133; switching the port 111 of the first multi-way valve 11 to communicate with the port 112 or 113, so that the first multi-way valve 11 communicates with the reaction device 200 and the second reagent 300; the port 121 of the second multi-way valve 12 is switched to communicate with the port 123 to communicate the second multi-way valve 12 with the reaction device 200 and the second pump 22. The second pump 22 is turned on, so that the second pump 22 drives the cleaning reagent to enter the reaction apparatus 200 along the second direction Y, and the cleaning reagent cleans the first reagent 400 remained in the reaction apparatus 200. The cleaning reagent may also enter the second pump 22, and further enter the liquid trap 31 and the waste liquid bottle 32, driven by the second pump 22.
As shown in fig. 4, before the second reaction is started or after the first reaction is performed, the type of the second reagent 300, for example, reagent I, to be introduced into the reaction device 200 for the second reaction may be determined, and the port 134 of the third multi-way valve 13, which is communicated with the reagent I, is communicated with the common port 133 by rotating the rotor 132 of the third multi-way valve 13; the port 111 of the first multi-way valve 11 is switched to communicate with the port 114, so that the first multi-way valve 11 communicates with the common port 133 (at this time, the common port 133 communicates with the reagent I) and the first pump 21. The first pump 21 is started, so that the first pump 21 drives the second reagent 300 to quickly fill the flow path of the first multi-way valve 11 with the second reagent 300, and the flow speed of the second reagent 300 is increased, specifically, the reagent I is filled in the pipelines of the second reagent 300 and the port 134, the pipeline inside the third multi-way valve 13, the pipeline between the common port 133 and the first multi-way valve 11, and the pipeline inside the first multi-way valve 11, so that in the subsequent second reaction, the reagent I does not need to be filled in the flow path of the second reagent 300 to the first multi-way valve 11 again, the reagent I can quickly enter the reaction device 200 to perform the second reaction, and meanwhile, bubbles are prevented from entering the reaction device 200 to influence the performance of the second reaction. Under the driving of the first pump 21, the reagent I can also fill the pipeline between the first multi-way valve 11 and the first pump 21, the pipeline inside the first pump 21, and the pipeline between the first pump 21 and the liquid collecting assembly, so as to facilitate the next reaction or the quick cleaning of the biomolecule analysis system 1000.
Before the second reaction is started, after the first reaction is performed, or when the biomolecule analysis system 1000 is cleaned, the port 111 of the first multi-way valve 11 may be switched to communicate with the port 112 or 113, and the port 121 of the second multi-way valve 12 may be switched to communicate with the port 123, so that the first multi-way valve 11 and the second multi-way valve 12 communicate with the common port 133 (in this case, the common port 133 may communicate with the reagent I) and the second pump 22. The second pump 22 is turned on so that the second pump 22 drives the second reagent 300 to quickly fill the flow path of the second reagent 300 to the first multi-way valve 11. Further, optionally, the port 111 of the first multi-way valve 11 may be communicated with the port 114, while the port 111 of the first multi-way valve 11 is communicated with the port 112 or 113, the port 121 of the second multi-way valve 12 is communicated with the port 123, so that the first multi-way valve 11 is communicated with the common port 133 (at this time, the common port 133 may be communicated with the reagent I) and the first pump 21, while the first multi-way valve 11 and the second multi-way valve 12 are communicated with the common port 133 and the second pump 22, and the first pump 21 and the second pump 22 are simultaneously turned on, so that the first pump 21 and the second pump 22 simultaneously drive the second reagent 300 to quickly fill the second reagent 300 into the flow path of the first multi-way valve 11, thereby increasing the flow rate of the second reagent 300.
As shown in fig. 2, when the second reaction is performed, the port 111 of the first multi-way valve 11 communicates with the port 112 or 113 to allow the first multi-way valve 11 to communicate with the reaction device 200 and the second reagent 300, and the port 121 of the second multi-way valve 12 communicates with the port 123 to allow the second multi-way valve 12 to communicate with the reaction device 200 and the second pump 22. The second pump 22 is turned on, so that the second pump 22 drives the second reagent 300 into the reaction device 200 along the second direction Y to perform the second reaction.
In combination with the above, the second reaction includes a plurality of sub-reactions, the process of performing the second reaction in the reaction apparatus 200 may be sub-reactions such as base extension reaction, signal acquisition, and radical cleavage in the reaction apparatus 200, and a cleaning process may be performed between the two sub-reactions. Specifically, the first multi-way valve 11 communicates the common port 133 with the reaction apparatus 200, the second multi-way valve 12 communicates the reaction apparatus 200 with the second pump 22, and the rotor 132 of the third multi-way valve 13 is rotated to communicate the port 134 of the third multi-way valve 13 communicating with the modified nucleotide with the common port 133 during the base extension reaction; when signals are collected, the rotor 132 of the third multi-way valve 13 is rotated, so that a port 134 in the third multi-way valve 13, which is communicated with the information collecting reagent, is communicated with the common port 133; when radical excision is performed, the rotor 132 of the third multi-way valve 13 is rotated, so that the port 134 of the third multi-way valve 13, which is communicated with the excision reagent, is communicated with the common port 133; when the cleaning process is performed, the rotor 132 of the third multi-way valve 13 is rotated so that the port 134 of the third multi-way valve 13, through which the cleaning agent is communicated, is communicated with the common port 133.
In one example, when the reaction apparatus 200 includes only one reaction unit, the sub-reactions of the second reaction and the cleaning process between the two sub-reactions may be sequentially performed on the reaction unit.
In another example, when the reaction apparatus 200 includes a plurality of reaction units, different sub-reactions in the second reaction may be performed on different reaction units, respectively. In the embodiment of the present application, the reaction apparatus 200 includes a first unit 201 and a second unit 202, the first unit 201 and the second unit 202 are respectively communicated with the port 112 and the port 113 of the first multi-way valve 11, so that different second reagents 300 can be respectively introduced into the first unit 201 and the second unit 202, and the first unit 201 and the second unit 202 can respectively perform different sub-reactions, thereby improving the overall efficiency of performing the second reaction.
For example, the second reaction includes a nucleic acid sequencing reaction including a plurality of repetitive reactions, one repetitive reaction including a base extension reaction, signal acquisition, and radical cleavage. While one of the first unit 201 and the second unit 202 is undergoing a base extension reaction or radical cleavage, a signal is collected from the other of the first unit 201 and the second unit 202. In one example, the sum of the reaction time required for the group cleavage and the reaction time required for the base extension reaction is approximately equal to the time required for signal acquisition.
The biomolecule analysis system 1000 may further include a signal acquisition device that may be used for signal acquisition, and in particular, the signal acquisition device may be an imaging device that may perform signal acquisition on the first unit 201 or the second unit 202 that is performing signal acquisition. Because only one of the first unit 201 and the second unit 202 can collect signals at the same time, the number of the signal collecting devices can be set to one set, and the signal collecting devices collect signals of the first unit 201 or the second unit 202 which is collecting signals, so that two sets of signal collecting devices are not needed, and the cost is saved.
In the description herein, reference to the description of the terms "certain embodiments," "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples" means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the application. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the feature. In the description of the present application, "a plurality" means at least two, e.g., two, three, unless specifically limited otherwise.
Although embodiments of the present application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present application, and that variations, modifications, substitutions and alterations of the above embodiments may be made by those of ordinary skill in the art within the scope of the present application, which is defined by the claims and their equivalents.
Claims (10)
1. A fluid path system for providing a solution environment for analyzing biomolecules, the analyzing biomolecules including performing a first reaction and a second reaction on a reaction device, the first reaction including coupling the biomolecules into the reaction device using a first reagent, the second reaction including detecting the biomolecules coupled into the reaction device using a second reagent, the fluid path system comprising:
the valve body assembly comprises a first multi-way valve and a second multi-way valve, the first multi-way valve can be communicated with the second reagent and the reaction device, and the second multi-way valve can be communicated with the first reagent and the reaction device; and
the driving assembly comprises a first pump and a second pump, the first pump is connected with the first multi-way valve, and the second pump is connected with the second multi-way valve;
under the condition that the first multi-way valve is communicated with the reaction device and the first pump, and the second multi-way valve is communicated with the reaction device and the first reagent, the first pump is used for driving the first reagent to enter the reaction device along a first direction so as to perform the first reaction;
and under the condition that the second multi-way valve is communicated with the reaction device and the second pump, and the first multi-way valve is communicated with the reaction device and the second reagent, the second pump is used for driving the second reagent to enter the reaction device along a second direction so as to perform the second reaction.
2. The fluid path system of claim 1, wherein the biomolecule is a nucleic acid, the first reaction comprises a hybridization reaction, and/or the second reaction comprises a sequencing reaction;
optionally, the valve body assembly further comprises a third multi-way valve, the third multi-way valve being communicable with the second reagent and the first multi-way valve;
optionally, the third multi-way valve comprises a stator and a rotor that are communicable, the third multi-way valve comprises a common port, the stator comprises a plurality of ports, the rotor comprises a communication groove, and the rotor is rotatable to communicate the common port with at least one of the ports through the communication groove.
3. The fluid path system of claim 1, wherein the first multi-way valve comprises a plurality of ports, the plurality of ports are connected to at least the second reagent, the reaction device and the first pump, respectively, and any two ports on the first multi-way valve can be communicated;
optionally, the reaction device comprises a first unit and a second unit, the first multi-way valve is a four-way valve, and four ports of the four-way valve are respectively connected with the second reagent, the first unit, the second unit and the first pump.
4. The fluid path system of claim 1, wherein the second multi-way valve comprises three ports, the three ports are respectively connected with the first reagent, the reaction device and the second pump, and any two ports of the second multi-way valve can be communicated;
optionally, the second multi-way valve is a three-way valve;
optionally, the reaction device comprises a plurality of channels, the number of the second multi-way valves and the number of the second pumps are not less than the number of the channels, and one second multi-way valve can be communicated with one channel and one second pump.
5. The fluid path system of claim 1, further comprising a manifold assembly in communication with the first pump, the manifold assembly configured to collect the first reagent after the first reaction; and/or
The collecting assembly is communicated with the second pump and is used for collecting the second reagent after the second reaction;
optionally, the manifold assembly is further configured to collect the second reagent driven by the first pump when the first pump and the second reagent are in communication through the first multi-way valve;
optionally, the manifold assembly includes a fluid collection piece and a waste fluid bottle, the fluid collection piece includes a first port and a plurality of second ports, the first port communicates with the plurality of second ports, the first pump communicates with the second ports, the second pump communicates with the second ports, and the waste fluid bottle communicates with the first port.
6. The fluid path system according to claim 1, wherein the first multi-way valve is capable of communicating the first pump and the second reagent and/or communicating the second pump and the second reagent after the first reaction is performed or before the second reaction is started, and the first pump and/or the second pump is configured to drive the second reagent to fill the flow path of the first multi-way valve with the second reagent;
optionally, the first direction is opposite the second direction.
7. A biomolecule analysis system, comprising the liquid path system according to any one of claims 1 to 6.
8. The biomolecule analysis system of claim 7, further comprising a reaction device connecting the first and second multi-way valves;
optionally, the biomolecule is a nucleic acid, the reaction device comprises a first unit and a second unit, and the biomolecule analysis system further comprises a signal acquisition device for acquiring a signal;
the second reaction is a nucleic acid sequencing reaction comprising a plurality of repetitive reactions, one of the repetitive reactions comprising a base extension reaction, signal acquisition, and radical cleavage;
and (b) performing the base extension reaction and/or the radical cleavage in one of the first unit and the second unit, and simultaneously performing the signal acquisition in the other of the first unit and the second unit by using the signal acquisition device.
9. A nucleic acid sequencing system comprising the fluid path system of any one of claims 1 to 6.
10. The nucleic acid sequence determination system of claim 9, further comprising a reaction device that removably connects the first and second multi-way valves.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911309913.0A CN110904206A (en) | 2019-12-18 | 2019-12-18 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
| PCT/CN2020/109734 WO2021120651A1 (en) | 2019-12-18 | 2020-08-18 | Liquid path system, biomolecule analysis system and nucleotide sequencing system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911309913.0A CN110904206A (en) | 2019-12-18 | 2019-12-18 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110904206A true CN110904206A (en) | 2020-03-24 |
Family
ID=69826349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911309913.0A Pending CN110904206A (en) | 2019-12-18 | 2019-12-18 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110904206A (en) |
| WO (1) | WO2021120651A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021120651A1 (en) * | 2019-12-18 | 2021-06-24 | 深圳市真迈生物科技有限公司 | Liquid path system, biomolecule analysis system and nucleotide sequencing system |
| WO2022068681A1 (en) * | 2020-09-29 | 2022-04-07 | 深圳市真迈生物科技有限公司 | Flow path selection value, system and method, storage medium, and application |
| CN114317703A (en) * | 2020-09-29 | 2022-04-12 | 深圳市真迈生物科技有限公司 | Nucleic acid sequence determination method, system, storage medium, and computer program product |
| WO2022073357A1 (en) * | 2020-10-10 | 2022-04-14 | 深圳市真迈生物科技有限公司 | Sequencing system and bearing apparatus |
| CN114682310A (en) * | 2020-12-31 | 2022-07-01 | 深圳市真迈生物科技有限公司 | Liquid path system, sequencing system and method |
| CN116618106A (en) * | 2023-07-21 | 2023-08-22 | 深圳赛陆医疗科技有限公司 | Fluid transportation system with variable flow direction, detection system and fluid transportation method thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114250144A (en) * | 2021-12-17 | 2022-03-29 | 深圳铭毅智造科技有限公司 | Liquid path system for gene sequencing |
| CN114480072A (en) * | 2022-01-27 | 2022-05-13 | 武汉生民医疗科技有限公司 | Cell capture system, method of controlling capture, and related apparatus |
| CN117384749A (en) * | 2023-07-05 | 2024-01-12 | 武汉华大智造科技有限公司 | Method for loading sequencing liquid onto sequencing slide, flow path system for gene sequencing and gene sequencer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108456748A (en) * | 2017-02-22 | 2018-08-28 | 深圳市瀚海基因生物科技有限公司 | The methods, devices and systems controlled are reacted to sequencing |
| CN211848007U (en) * | 2019-12-18 | 2020-11-03 | 深圳市真迈生物科技有限公司 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6889710B2 (en) * | 2002-11-15 | 2005-05-10 | Air Products And Chemicals, Inc. | Rotary sequencing valve with flexible port plate |
| CN105733936B (en) * | 2014-12-12 | 2017-11-17 | 深圳华大基因研究院 | Gene sequencer |
| CN105199949B (en) * | 2015-09-15 | 2017-12-12 | 深圳市瀚海基因生物科技有限公司 | The fluid control device of gene sequencing |
| CN206553527U (en) * | 2017-02-22 | 2017-10-13 | 深圳市瀚海基因生物科技有限公司 | sequence detection system |
| CN206553528U (en) * | 2017-02-22 | 2017-10-13 | 深圳市瀚海基因生物科技有限公司 | Sequencing control system |
| CN108949939B (en) * | 2017-05-26 | 2023-04-25 | 深圳市真迈生物科技有限公司 | Method, device and system for controlling sequence determination reaction |
| CN209065879U (en) * | 2018-08-01 | 2019-07-05 | 深圳市瀚海基因生物科技有限公司 | Sequence Detection System |
| CN110904206A (en) * | 2019-12-18 | 2020-03-24 | 深圳市真迈生物科技有限公司 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
-
2019
- 2019-12-18 CN CN201911309913.0A patent/CN110904206A/en active Pending
-
2020
- 2020-08-18 WO PCT/CN2020/109734 patent/WO2021120651A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108456748A (en) * | 2017-02-22 | 2018-08-28 | 深圳市瀚海基因生物科技有限公司 | The methods, devices and systems controlled are reacted to sequencing |
| CN211848007U (en) * | 2019-12-18 | 2020-11-03 | 深圳市真迈生物科技有限公司 | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021120651A1 (en) * | 2019-12-18 | 2021-06-24 | 深圳市真迈生物科技有限公司 | Liquid path system, biomolecule analysis system and nucleotide sequencing system |
| WO2022068681A1 (en) * | 2020-09-29 | 2022-04-07 | 深圳市真迈生物科技有限公司 | Flow path selection value, system and method, storage medium, and application |
| CN114317703A (en) * | 2020-09-29 | 2022-04-12 | 深圳市真迈生物科技有限公司 | Nucleic acid sequence determination method, system, storage medium, and computer program product |
| WO2022073357A1 (en) * | 2020-10-10 | 2022-04-14 | 深圳市真迈生物科技有限公司 | Sequencing system and bearing apparatus |
| CN114682310A (en) * | 2020-12-31 | 2022-07-01 | 深圳市真迈生物科技有限公司 | Liquid path system, sequencing system and method |
| CN114682310B (en) * | 2020-12-31 | 2023-12-05 | 深圳市真迈生物科技有限公司 | Liquid path system, sequencing system and method |
| CN116618106A (en) * | 2023-07-21 | 2023-08-22 | 深圳赛陆医疗科技有限公司 | Fluid transportation system with variable flow direction, detection system and fluid transportation method thereof |
| CN116618106B (en) * | 2023-07-21 | 2023-09-26 | 深圳赛陆医疗科技有限公司 | Fluid transportation system with variable flow direction, detection system and fluid transportation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021120651A1 (en) | 2021-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110904206A (en) | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system | |
| AU2009201529B2 (en) | Apparatus For Polynucleotide Detection and Quantitation | |
| EP1608952B1 (en) | Assay apparatus and method using microfluidic arrays | |
| CN213327664U (en) | Rotary valve, liquid path system and nucleic acid sequence determination system | |
| CN114682310B (en) | Liquid path system, sequencing system and method | |
| WO1997031105A1 (en) | Method for treating biopolymers, microorganisms or materials by using more than one type of magnetic particles | |
| US20190030526A1 (en) | Magnetic Separation | |
| US20090093064A1 (en) | Method of determining the presence of a mineral within a material | |
| CN213655273U (en) | Liquid path system and detection system | |
| EP1718411B1 (en) | A device for analysing an interaction between target and probe molecules | |
| JP2020516852A (en) | Flow cell liquid degassing system and method | |
| CN211848007U (en) | Liquid path system, biomolecule analysis system and nucleic acid sequence measuring system | |
| US20050106607A1 (en) | Biochip containing reaction wells and method for producing same and use thereof | |
| JP2005528118A (en) | New methods for high-throughput integrated chemistry and biochemical reactions | |
| Meldrum et al. | ACAPELLA-1K, a capillary-based submicroliter automated fluid handling system for genome analysis | |
| US20020048754A1 (en) | Apparatus and method for processing multiple arrays of biological probes | |
| WO2022068681A1 (en) | Flow path selection value, system and method, storage medium, and application | |
| JP6637172B2 (en) | Modular flow cell and method of sequencing | |
| JPH07508407A (en) | Methods and systems for molecular biological diagnosis | |
| CN108456748B (en) | Method, device and system for controlling sequence determination reaction | |
| CN214662228U (en) | Flow path selection valve, flow cell assembly, liquid path system and sequencing system | |
| WO2021233186A1 (en) | Biological target digital quantitative detection method and system based on virtual segmentation technology | |
| JP2008157948A (en) | Biochip kit and examination method for biological sample | |
| CN108949939B (en) | Method, device and system for controlling sequence determination reaction | |
| CN114317702A (en) | Rotary valve, liquid path system and nucleic acid sequence determination system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40015654 Country of ref document: HK |