Molecular hybridization instrument and liquid path system
Through the automated liquid distribution solution of liquid system and molecular hybridizer, the problem of cumbersome reagent ratio and reagent deterioration in molecular hybridization is solved, achieving efficient and accurate reagent use and reducing waste.
Patent Information
- Application Number
- CN202510053199.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-14
- Publication Date
- 2025-02-25
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In the prior art, the proportion of reagents with different components required during molecular hybridization is complicated, which makes artificial liquid dispensing time-consuming and labor-intensive, reduces detection efficiency, and the reagents are prone to volatilization or crystallization and deterioration due to contact with air.
It provides a liquid system and a molecular hybridizer, through the combination of multiple reagent supply components, quantification devices, liquid mixing containers, liquid injection pipelines, gate devices and control modules, to automatically calculate the reagent volume and obtain reagents automatically to avoid waste and deterioration.
It realizes automated reagent dispensing liquid, precise dispensing liquid, avoids waste of reagents, and stores reagents in sealed containers to prevent volatilization or crystallization caused by contact with air.
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Figure CN119499957A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of medical equipment, and in particular to a molecular hybridization instrument and a liquid circuit system. Background Art
[0002] In the field of molecular diagnosis in the medical IVD (In Vitro Diagnostic) industry, the reverse hybridization method is usually used to hybridize the probe with the amplified DNA sample to be tested. The probe has a sequence homologous to the DNA sample to be tested, and the DNA sample to be tested has a biotin marker. The probe can bind to the biotin marker of the DNA sample to be tested, and then a color development reaction can show a hybridization signal, thereby determining most or all of the alleles of the gene.
[0003] In the process of liquid phase hybridization on the membrane strip, the membrane strip needs to be immersed in reagents of different components at different stages. In the related technology, the proportions of reagents of different components are mostly made by manual liquid preparation, and then the liquid addition and waste liquid discharge operations are performed through the liquid addition system. However, the manual liquid preparation method is time-consuming and labor-intensive, which seriously restricts the detection efficiency. Summary of the invention
[0004] The present application aims to provide a molecular hybridization instrument and a liquid path system, which can automatically calculate the reagent liquid volume according to the components of the required preset mixed reagents, and automatically obtain the reagents, thereby avoiding waste of reagents and avoiding volatilization or even crystal deterioration caused by contact with air.
[0005] According to a first aspect of the present application, the present application provides a fluid circuit system, comprising: A plurality of reagent supply assemblies, wherein the plurality of reagent supply assemblies are used to provide a plurality of types of reagents; A quantitative device, used to obtain a preset amount of reagent from the reagent supply assembly; a liquid mixing container, the liquid mixing container being in communication with the quantitative device, and being used for receiving a preset liquid amount of reagent obtained by the quantitative device, and being able to mix at least two types of reagents into a preset mixed reagent; A plurality of liquid injection pipelines, the plurality of liquid injection pipelines being in communication with the liquid mixing container and being used for injecting the preset mixed reagent into a plurality of sample storage positions in the sample storage group of the hybridization box; A gating device, the gating device is connected between the plurality of the reagent supply components and the quantitative device, and is connected between the quantitative device and the liquid mixing container, the gating device is used to selectively connect the reagent supply components with the quantitative device, and connect the quantitative device with the liquid mixing container after the quantitative device obtains a preset amount of reagent; A control module, wherein the control module is electrically connected to the quantitative device and the gating device, and the control module is used to control the gating device to selectively connect different reagent supply components with the quantitative device according to the components of the preset mixed reagent, and can also control the quantitative device to obtain different preset liquid amounts of reagents from different reagent supply components according to the components of different types of preset mixed reagents.
[0006] In one embodiment, it also includes a cleaning liquid supply pipeline, which is used to provide cleaning liquid. The gating device is also connected between the cleaning liquid supply pipeline and the quantitative device, and is used to selectively connect the cleaning liquid supply pipeline with the quantitative device; the control module can also control the gating device to connect the cleaning liquid supply pipeline with the quantitative device after each preparation of the preset mixed reagent is completed, and also control the quantitative device to obtain cleaning liquid from the cleaning liquid supply pipeline, and transport the cleaning liquid to the mixed liquid container through the quantitative device.
[0007] In one embodiment, the reagent supply assembly includes a plurality of first reagent supply pipelines and a plurality of second reagent supply pipelines, wherein the plurality of first reagent supply pipelines are used to connect to a first reagent supply source of a plurality of first type reagents, and the plurality of second reagent supply pipelines are used to connect to a second reagent supply source of a plurality of second type reagents; The liquid circuit system further includes a plurality of three-way solenoid valves, each of which corresponds to each of the plurality of second reagent supply pipelines. The three-way solenoid valves have a common end, a normally closed end, and a normally open end. The common end is interconnected with the gating device through the second reagent supply pipeline. The normally closed end is used to communicate with the second reagent supply source, and the normally open end is interconnected with the liquid mixing container. The three-way solenoid valve is electrically connected to the control module. The gating device is connected between a plurality of the first reagent supply pipelines and the quantitative device, and is also connected between a plurality of the second reagent supply pipelines and the quantitative device; The control module controls the gating device to selectively connect different first reagent supply pipelines to the quantitative device according to the components of the preset mixed reagent, and can also control the quantitative device to obtain different first preset liquid volumes of the first reagent from different first reagent supply pipelines according to the components of different types of preset mixed reagents; and / or, The control module controls the gating device to connect the cleaning liquid supply pipeline with the quantitative device, and after the quantitative device extracts a preset content of cleaning liquid, controls the gating device to selectively connect different second reagent supply pipelines with the quantitative device, and can control the quantitative device to inject a preset content of cleaning liquid into the second reagent supply pipeline according to the components of different types of preset mixed reagents, control the normally closed end of the three-way solenoid valve to open, control the quantitative device to work, and use the transported cleaning liquid to transport the second preset liquid amount of the second reagent to the mixed liquid container through the common end.
[0008] In one embodiment, the gating device includes a main body, a core body and a rotating drive assembly, the main body having a main channel, a cleaning liquid branch channel, a plurality of first branch channels and a plurality of second branch channels, the core body being rotatably connected to the main body, the core body being provided with a transition channel, one end of the transition channel being always connected to the main channel, the main channel being connected to the quantitative device, the other end of the transition channel being connected to the cleaning liquid branch channel, or a different first branch channel, or a different second branch channel; the cleaning liquid branch channel being connected to the cleaning liquid supply pipeline, the first branch channel being connected to the first reagent supply pipeline, and the second branch channel being connected to the second reagent supply pipeline; the core body is transmission-connected to the rotating drive assembly for driving the core body to rotate so as to switch the other end of the transition channel to be connected to the cleaning liquid branch channel, or a different first branch channel, or a different second branch channel.
[0009] In one embodiment, a cleaning liquid delivery device is further included, wherein the cleaning liquid delivery device is connected between the cleaning liquid supply pipeline and the mixed liquid container, and the cleaning liquid delivery device is also electrically connected to the control module. The control module can also control the cleaning liquid delivery device to deliver the cleaning liquid to the mixed liquid container after completing the preparation of all preset mixed reagents.
[0010] In one embodiment, a mixing device is further included, wherein the mixing device is communicated with the liquid mixing container and is electrically connected to the control module, and the control module is used to mix at least two types of reagents after the quantitative device provides at least two reagents required for the preset mixed reagent.
[0011] In one embodiment, a heating device is further included, wherein the heating device is connected to the mixed liquid container, and the heating device is electrically connected to the control module, and the control module is used to control the heating device to heat the mixed liquid container to a preset temperature according to the preset mixed reagent that is preheated as needed.
[0012] In one embodiment, it further comprises a waste liquid discharge pipeline, wherein the waste liquid discharge pipeline is used to discharge the waste liquid in the hybridization box.
[0013] In one embodiment, a diverter device is further included, and the diverter device is connected to the waste liquid discharge pipeline for discharging the preset waste liquid.
[0014] According to the second aspect of the present application, the present application provides a molecular hybridization instrument, comprising the above-mentioned liquid circuit system.
[0015] According to the molecular hybridization instrument and liquid circuit system of the above embodiment, the gating device can be automatically controlled to select the reagent supply assembly of the required component according to the components of the preset mixed reagent to be connected to the quantitative device, and the quantitative device can also be controlled according to the components of different types of preset mixed reagents to obtain the reagent of the preset liquid amount required for the component from different reagent supply assemblies, so as to automatically calculate the reagent liquid amount and automatically obtain the reagent. Compared with the manual liquid preparation method used in the related art, the liquid can be accurately prepared to avoid reagent waste. In addition, the reagents are stored in a sealed reagent storage container, which can also avoid the problem of volatilization or even crystallization and deterioration caused by contact with air. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Figure 1 A schematic diagram of a fluid circuit system provided in the related art; Figure 2 It is a structural block diagram of the liquid circuit system provided in the related art; Figure 3 A schematic plan view of the liquid path system provided in the present application applied to a molecular hybridization instrument; Figure 4 A schematic diagram of the structure of a liquid mixing container in the liquid circuit system provided in this application; Figure 5 A three-dimensional diagram of a gating device in a liquid circuit system provided in the present application; Figure 6 A cross-sectional view of a gating device in a liquid circuit system provided in the present application; Figure 7 A top view of the molecular hybridization apparatus provided in this application Figure 1 ; Figure 8 A front view of a waste liquid collection component in a molecular hybridization instrument provided in the present application; Fig. 9 for Figure 8 Cross-section view in the AA direction; Fig.10 A top view of the molecular hybridization apparatus provided in this application Figure 2 ; Fig.11 A three-dimensional diagram of a hybridization box in a molecular hybridization instrument provided in the present application; Fig.12 This is a schematic diagram of the injection mechanism connected to the injection pipeline in the molecular hybridization instrument provided in the present application.
[0017] Reference numerals: Reagent supply assembly 10, first reagent supply pipeline 11, first reagent supply source 111, second reagent supply pipeline 12, second reagent supply source 121, connecting pipeline 122, three-way solenoid valve 123, common end 1231, normally closed end 1232, normally open end 1233, quantitative device 20, mixing container 30, cup body 31, cover body 32, first suction interface 321, second suction interface 322, reagent input interface 323, reagent output interface 324, cleaning liquid input interface 325, air outlet 326, injection pipeline 40, peristaltic pump 41, gating device 50, main body 51, main channel 511, cleaning liquid branch channel 512, first branch channel 513, second branch channel 514, core body 52, transition channel 521, rotation drive assembly 53, control module 60, cleaning liquid supply pipeline 70, cleaning liquid supply source 71, liquid supply pipeline 72, first liquid outlet pipeline 73, second liquid outlet pipeline 74, cleaning liquid delivery device 80, mixing device 90, waste liquid discharge pipeline 91, diverter device 92, cleaning liquid collecting device 93, cleaning liquid collecting pipeline 94, hybridization box 100, sample storage group 101, sample storage position 102, liquid addition and discharge structure 200, injection needle 201, discharge needle 202. DETAILED DESCRIPTION
[0018] The present application is further described in detail below by specific embodiments in conjunction with the accompanying drawings. Wherein similar elements in different embodiments adopt associated similar element numbers. In the following embodiments, many detailed descriptions are intended to enable the present application to be better understood. However, those skilled in the art can easily recognize that some of the features can be omitted in different situations, or can be replaced by other elements, materials, and methods. In some cases, some operations related to the present application are not shown or described in the specification, in order to avoid the core part of the present application being overwhelmed by too much description, and for those skilled in the art, it is not necessary to describe these related operations in detail, and they can fully understand the related operations based on the description in the specification and the general technical knowledge in the art.
[0019] In addition, the features, operations or characteristics described in the specification can be combined in any appropriate manner to form various implementations, and the operation steps involved in each embodiment can also be replaced or adjusted in order in a manner that is obvious to those skilled in the art. Therefore, the specification and drawings are only for the purpose of clearly describing a certain embodiment, and do not mean that the composition and / or order are necessary.
[0020] The serial numbers assigned to the components herein, such as "first", "second", etc., are only used to distinguish the objects described and do not have any order or technical meaning. The "connection" and "coupling" mentioned in this application, unless otherwise specified, include direct and indirect connections (couplings).
[0021] In the field of molecular diagnosis of the medical IVD (In Vitro Diagnostic) industry, the probe containing the oligonucleotide sequence is fixed on the membrane strip (nitrocellulose membrane or nylon membrane) by reverse dot hybridization, and then the amplified DNA sample to be tested (usually PCR-specific amplification and biotin-labeled DNA sample to be tested) is hybridized with it, so that the DNA sample to be tested will bind to the probe with the homologous sequence to form a stable double-stranded structure. Since the DNA sample to be tested has a biotin marker, the hybridization signal can be displayed after the corresponding color reaction, and most or all alleles of the gene can be determined.
[0022] In the process of liquid phase hybridization on the membrane strip, the membrane strip needs to be immersed in reagents of different components at different stages, and the ratio, concentration, temperature control and other processes of reagents of different components are cumbersome and complicated. In the related art, reagents of different components are prepared manually, and then liquid is added and waste liquid is discharged through the liquid adding system. However, manual liquid preparation requires the calculation of liquid consumption according to the sample volume and then the liquid is prepared. The manual liquid preparation method will prepare more reagents to prevent insufficient liquid during the experiment, which will also bring about the problem of reagent waste. In addition, if the extra reagents are left for too long and in contact with air for a long time, the reagents may volatilize and produce a large amount of crystals.
[0023] In response to the above problems, the present application provides a liquid circuit system and a molecular hybridization instrument, which can automatically calculate the reagent liquid volume according to the components of the required preset mixed reagents and automatically obtain the reagents, thereby avoiding waste of reagents and avoiding volatilization or even crystallization deterioration caused by contact with air.
[0024] See also Figure 1-Figure 7 As shown, the liquid circuit system provided in this embodiment includes a plurality of reagent supply components 10 , a quantitative device 20 , a liquid mixing container 30 , a plurality of liquid injection pipelines 40 , a gating device 50 and a control module 60 .
[0025] The plurality of reagent supply assemblies 10 are used to provide various types of reagents, wherein the plurality of reagent supply assemblies 10 are in communication with reagent storage containers for storing various different types of reagents.
[0026] The liquid circuit system provided in the present application is applied to a molecular hybridization instrument. For a molecular hybridization instrument, in the process of hybridization between a DNA sample to be tested and a probe containing an oligonucleotide sequence, steps such as preheating, denaturation, hybridization, membrane washing, incubation, cleaning, color development, and cleaning are required. The reagents used in each step are also different, and the reagents used in each step are all preset mixed reagents formed by mixing at least two different types of reagents. In addition, the types and liquid volumes of the preset mixed reagents corresponding to different steps are different. The usual practice is to use manual liquid preparation, and to ensure the liquid volume, more reagents will be prepared. Not only is the liquid preparation efficiency low, but it is also easy to waste reagents. At the same time, the liquid preparation process is also prone to volatilization of reagents due to contact with air, and even a large amount of crystals are produced and deteriorated.
[0027] In the present application, the reagent storage container connected to the reagent supply assembly 10 can ensure that the reagent is in a sealed state, thereby preventing the reagent from contacting the air and causing volatilization or even crystallization and deterioration.
[0028] The quantitative device 20 is used to obtain a preset amount of reagent from the reagent supply assembly 10 , and different types of reagents can be mixed to obtain a preset mixed reagent.
[0029] It should be noted that for different types of preset mixed reagents used in different experimental processes, some of their components are the same, but the liquid volume may be different. Therefore, for different types of preset mixed reagents, the content of the reagents with the same components may be different. The quantitative device 20 can select the preset liquid volume of the required reagent according to the type of the preset mixed reagent to obtain it in an automatic manner.
[0030] The liquid mixing container 30 is in communication with the quantitative device 20 . The liquid mixing container 30 is used to receive a preset liquid volume of reagent obtained by the quantitative device 20 , and can mix at least two types of reagents into a preset mixed reagent.
[0031] Of course, for different preset mixed reagents required for different experimental steps, the types and liquid volumes of reagents required are also different.
[0032] A plurality of liquid injection pipes 40 are connected to the liquid mixing container 30, and the Fig.11 As shown, the plurality of injection lines 40 are used to inject the preset mixed reagent into the plurality of sample storage positions 102 in the sample storage group 101 of the hybridization box 100. Figure 1 As shown, each injection pipeline 40 is provided with a peristaltic pump 41, and the preset mixed reagent is pumped to the multiple sample storage positions 102 in the sample storage group 101 by the peristaltic pump 41. Among them, the DNA sample to be tested is pre-stored in the sample storage position 102, and the sample storage group 101 is Fig.11The portion selected by the dotted line frame in the middle, wherein a plurality of sample storage groups 101 are arranged in parallel along the length direction of the hybridization box 100, and each sample storage group 101 is provided with a plurality of sample storage positions 102 arranged along the width direction of the hybridization box 100, and the preset mixed reagent required for each step is added to the sample storage position 102. The sample storage position 102 may be a slot-type structure, so as to store samples and accommodate the preset mixed reagent.
[0033] The gating device 50 is connected between the plurality of reagent supply components 10 and the quantitative device 20, and is connected between the quantitative device 20 and the liquid mixing container 30. The gating device 50 is used to selectively connect the reagent supply component 10 with the quantitative device 20, and connect the quantitative device 20 with the liquid mixing container 30 after the quantitative device 20 obtains a preset amount of reagent. When the quantitative device 20 is connected with the liquid mixing container 30, the quantitative device 20 is indirectly connected with the liquid mixing container 30 by means of the gating device 50.
[0034] In a specific embodiment, for a preset mixed reagent, for example, if a reagent of component A and component B is required, the gating device 50 connects the quantitative device 20 with the reagent supply assembly 10 corresponding to component A, and obtains a preset amount of component A reagent through the quantitative device 20. After the quantitative device 20 obtains the preset amount of component A reagent, the gating device 50 connects the quantitative device 20 with the mixed liquid container 30, and the quantitative device 20 delivers the preset amount of component A reagent to the mixed liquid container. For a reagent of component B, the gating device 50 connects the quantitative device 20 with the reagent supply assembly 10 corresponding to component B, and obtains a preset amount of component B reagent through the quantitative device 20. After the quantitative device 20 obtains the preset amount of component B reagent, the gating device 50 connects the quantitative device 20 with the mixed liquid container 30, and the quantitative device 20 delivers the preset amount of component B reagent to the mixed liquid container. Thus, the two types of reagents, component A and component B, are mixed in the mixed liquid container 30 to form a preset mixed reagent.
[0035] The control module 60 is electrically connected to the quantitative device 20 and the gating device 50. The control module 60 is used to control the gating device 50 to selectively connect different reagent supply components 10 containing required components with the quantitative device 20 according to the components of the preset mixed reagent. The control module 60 can also control the quantitative device 20 to obtain reagents with different preset liquid volumes from different reagent supply components 10 according to the components of different types of preset mixed reagents, that is, the quantitative device 20 can obtain the reagent with the preset liquid volume corresponding to the required component according to the liquid volume of the component.
[0036] Of course, after the quantitative device 20 obtains reagents of different preset liquid volumes from different reagent supply components 10, the control module 60 can also connect the gating device 50 between the quantitative device 20 and the mixing liquid container 30, so that the quantitative device 20 can provide the obtained preset liquid volume of reagent to the mixing liquid container 30 through the gating device 50 with the help of the gating device 50.
[0037] In this way, the gating device 50 can be automatically controlled to select the reagent supply assembly 10 of the required component to be connected to the quantitative device 20 according to the components of the preset mixed reagent. The quantitative device 20 can also be controlled according to the components of different types of preset mixed reagents to obtain the reagent of the preset liquid amount required for the component from different reagent supply assemblies 10, so as to automatically calculate the reagent liquid amount and automatically obtain the reagent. Compared with the manual liquid preparation method used in the related art, the liquid can be accurately prepared to avoid reagent waste. In addition, the reagents are stored in a sealed reagent storage container, which can also avoid the problem of volatilization or even crystallization and deterioration caused by contact with air.
[0038] However, after the mixing container 30 completes the preparation of the preset mixed reagent, when preparing another type of preset mixed reagent, in order to avoid the residual liquid of the previous preset mixed reagent forming in the mixing container 30 and affecting the composition of the subsequent preparation, therefore, see Figure 1 As shown, the liquid circuit system provided by the present application also includes a cleaning liquid supply pipeline 70, and the cleaning liquid supply pipeline 70 is used to provide cleaning liquid, wherein one end of the cleaning liquid supply pipeline 70 is connected to a cleaning liquid supply source 71, and the cleaning liquid supply source 71 stores cleaning liquid. The gating device 50 is also connected between the cleaning liquid supply pipeline 70 and the quantitative device 20, and the gating device 50 is also used to selectively connect the cleaning liquid supply pipeline 70 with the quantitative device 20. The control module 60 can also control the gating device 50 to connect the cleaning liquid supply pipeline 70 with the quantitative device 20 after each liquid preparation of the preset mixed reagent is completed, and the quantitative device 20 obtains the cleaning liquid from the cleaning liquid supply pipeline 70. The control module 60 also controls the quantitative device 20 to obtain the cleaning liquid from the cleaning liquid supply pipeline 70, and then delivers the cleaning liquid to the mixed liquid container 30 through the quantitative device 20, so that the mixed liquid container 30 that completes the liquid preparation of the previous preset mixed reagent is cleaned by the cleaning liquid.
[0039] In one embodiment, the cleaning liquid provided by the cleaning liquid supply pipeline 70 is water. Of course, in other embodiments, cleaning liquids with other components can also be selected. The specific selection can be made according to actual conditions and is not limited here.
[0040] See also Figure 1As shown, the reagent supply assembly 10 includes a plurality of first reagent supply pipelines 11 and a plurality of second reagent supply pipelines 12, wherein the plurality of first reagent supply pipelines 11 are used to connect a first reagent supply source 111 of a plurality of first type reagents, and the plurality of second reagent supply pipelines 12 are used to connect a second reagent supply source 121 of a plurality of second type reagents, wherein the first type reagents and the second type reagents are distinguished in the present application according to their required liquid volumes, the first type reagents require a larger liquid volume, while the second type reagents require a trace amount of liquid, and for the trace amount of the second type reagent, the method of obtaining the reagent is different from the method of obtaining the first type reagent.
[0041] Of course, in other embodiments, the first type of reagent and the second type of reagent may be reagents that need to be stored in a refrigerator and reagents that need to be stored at room temperature, respectively. The specific selection is based on actual needs and is not limited here.
[0042] In the present application, the second type of reagent is a reagent that requires a trace amount of liquid. In this regard, the liquid circuit system provided in the present application also includes a plurality of three-way solenoid valves 123, and the plurality of three-way solenoid valves 123 are electrically connected to the control module 60. The plurality of three-way solenoid valves 123 correspond to the plurality of second reagent supply pipelines 12, respectively, and the three-way solenoid valves 123 have a common end 1231, a normally closed end 1232, and a normally open end 1233. The common end 1231 is interconnected with the gating device 50 through the second reagent supply pipeline 12, the normally closed end 1232 is used to communicate with the second reagent supply source 121, and the normally open end 1233 is interconnected with the mixing container 30. Among them, the second reagent is stored in the second reagent supply source 121, and the second reagent supply source 121 can be a sealed container.
[0043] The gate device 50 is connected between the plurality of first reagent supply pipelines 11 and the quantitative device 20 , and is also connected between the plurality of second reagent supply pipelines 12 and the quantitative device 10 .
[0044] When the preset mixed reagent only needs to be provided by the first type of reagent through the first reagent supply pipeline 11, the control module 60 controls the selection device 50 to selectively connect different first reagent supply pipelines 11 with the quantitative device 20 according to the components of the preset mixed reagent, and can also control the quantitative device 20 to obtain different first preset liquid volumes of the first reagent from different first reagent supply pipelines 11 according to the components of different types of preset mixed reagents.
[0045] When the preset mixed reagent only needs to be provided by the second reagent supply line 12 as the second type of reagent, the control module 60 controls the gating device 50 to connect the cleaning liquid supply line 70 with the quantitative device 20, and after the quantitative device 20 extracts the cleaning liquid of the preset content, the control gating device 50 can selectively connect different second reagent supply lines 12 with the quantitative device 20, and can control the quantitative device 20 to inject the cleaning liquid of the preset content into the second reagent supply line according to the components of different types of preset mixed reagents, control the normally closed end 1232 of the three-way solenoid valve 123 to open, and control the quantitative device 20 to work, that is, the quantitative device 20 provides the cleaning liquid of the preset content delivered to the second reagent supply line 12 with the power to continue moving, and then with the help of the delivered cleaning liquid, the second reagent of the second preset liquid volume is delivered to the mixed liquid container 30 through the common end 1231 of the three-way solenoid valve 123 by the connecting line 122.
[0046] It should be noted that the quantitative device 20 is similar to a plunger pump and can quantitatively extract the first reagent or the second reagent by suction. After the quantitative device 20 injects the cleaning liquid into the second reagent supply pipeline 12, the cleaning liquid with a preset content can make the second reagent supply pipeline 12 maintain an air column of a preset length. Under the action of the power provided by the quantitative device, the normally closed end 1233 can generate a negative pressure, thereby driving the second preset liquid amount of the second reagent to be transported to the mixing container 30 through the common end 1231 and the connecting pipeline 122.
[0047] In other embodiments, the preset mixed reagent may include at least one first reagent and may also include at least one second reagent. Therefore, the control module 60 may perform control according to the component types of the preset mixed reagent.
[0048] See also Figure 5 and Figure 6 As shown, the gating device 50 includes a main body 51, a core 52 and a rotating drive assembly 53. The main body 51 has a main channel 511, a cleaning liquid branch channel 512, a plurality of first branch channels 513 and a plurality of second branch channels 514. The core 52 is rotatably connected to the main body 51. The core 51 is provided with a transition channel 521. One end of the transition channel 521 is always connected to the main channel 511. The main channel 511 is connected to the quantitative device 20. The other end of the transition channel 521 is connected to the cleaning liquid branch channel 512, or a different first branch channel 513, or a different second branch channel 514. The cleaning liquid branch channel 512 is connected to the cleaning liquid supply pipeline 70, the first branch channel 513 is connected to the first reagent supply pipeline 11, and the second branch channel 514 is connected to the second reagent supply pipeline 12. The core 52 is in transmission connection with the rotary drive assembly 53 , and the rotary drive assembly 53 is used to drive the core 52 to rotate so as to switch the other end of the transition channel 521 to communicate with the cleaning liquid branch channel 512 , or a different first branch channel 513 , or a different second branch channel 514 .
[0049] In the present application, a reagent supply channel is usually also provided on the main body 51, wherein one end of the reagent supply channel is always connected to the mixing liquid container 30, and the other end of the transition channel 521 can also be switched and connected to the other end of the reagent supply channel during the rotation of the core 51 relative to the main body 51, and the preset liquid amount of reagent, cleaning liquid, etc. obtained by the quantitative device 20 can be provided to the mixing liquid container 30 through the reagent supply channel.
[0050] Continue to see Figure 1 As shown, the liquid circuit system provided in this embodiment also includes a cleaning liquid delivery device 80, which is connected between the cleaning liquid supply pipeline 70 and the mixed liquid container 30. The cleaning liquid delivery device 80 is also electrically connected to the control module 60. The control module 60 can also control the cleaning liquid delivery device 90 to deliver the cleaning liquid to the mixed liquid container 30 after completing the preparation of all preset mixed reagents, so as to clean the mixed liquid container 30 after completing the preparation of all preset mixed reagents.
[0051] In a specific embodiment, a three-way valve body 81 is also provided between the cleaning liquid conveying device 80 and the cleaning liquid supply pipeline 70, the three-way valve body 81 having a liquid inlet end, a first liquid outlet end and a second liquid outlet end, the cleaning liquid supply pipeline 70 includes a liquid supply pipeline 72, a first liquid outlet pipeline 73 and a second liquid outlet pipeline 74, one end of the liquid supply pipeline 72 is connected to the liquid inlet end, the other end of the liquid supply pipeline 72 is connected to the cleaning liquid supply source 71, one end of the first liquid outlet pipeline 73 is connected to the first liquid outlet end, the other end of the first liquid outlet pipeline 73 is connected to the selection device 50, one end of the second liquid outlet pipeline 74 is connected to the second liquid outlet end, and the other end of the second liquid outlet pipeline 74 is connected to the mixing container 30.
[0052] The cleaning liquid delivery device 80 is usually a syringe pump, which can deliver the cleaning liquid to the mixing container 30 through the liquid supply pipeline 72 and the second liquid outlet pipeline 74 in sequence by pumping.
[0053] To facilitate mixing of at least two reagents in the mixing container 30, the liquid path system provided in this embodiment also includes a mixing device 90, which is connected to the mixing container 30 and electrically connected to the control module 60. The control module 60 is used to mix at least two types of reagents after the quantitative device 20 provides at least two reagents required for the preset mixed reagent.
[0054] The mixing device 90 uses a diaphragm pump to mix the reagents in the mixing container 30 by repeated suction.
[0055] Combination Figure 1 and Figure 4As shown, the mixing liquid container 30 is usually composed of a cup body 31 and a cover body 32. The cover body 32 has a sealing cover and is at the cup mouth of the cup body 31. The cover body 32 is also provided with a first suction interface 321, a second suction interface 322, a reagent input interface 323, a reagent output interface 324, a cleaning liquid input interface 325 and an air outlet 326, wherein the first suction interface 321 and the second suction interface 322 are both connected to the mixing device 90 so as to repeatedly suck the reagent for mixing, the reagent input interface 323 is connected to the gating device 50, the reagent output interface 324 is connected to the injection pipeline 40, the cleaning liquid input interface 325 is connected to the cleaning liquid supply pipeline 70, and the air outlet 326 is connected to the interior of the cup body 31 to keep the interior of the cup body 31 connected with the outside world, so as to facilitate the injection of reagents or cleaning liquid into the cup body.
[0056] In some embodiments, the preset mixed reagent also needs to be heated to a preset temperature. Therefore, the liquid path system provided in this embodiment also includes a heating device (not shown in the figure), which is connected to the mixed liquid container 30. The heating device is electrically connected to the control module 60. The control module 60 is used to control the heating device to heat the mixed liquid container 30 to a preset temperature according to the preset mixed reagent that needs to be preheated, so that the preset mixed reagent meets the temperature requirements required for the experiment.
[0057] Before adding the preset mixed reagent to the sample storage position 102 of the hybridization box 100 , the waste liquid generated in the previous experiment needs to be discharged. Therefore, the liquid system provided in the present application also includes a waste liquid discharge pipeline 91 , which is used to discharge the waste liquid in the sample storage position 102 of the hybridization box 100 .
[0058] See also Figure 7 and Fig.12 As shown, a liquid adding and discharging structure 200 is provided in the molecular hybridization instrument, and the liquid adding and discharging structure 200 includes a plurality of liquid injection needles 201 and a plurality of liquid discharging needles 202, and the plurality of liquid injection needles 201 and the plurality of liquid discharging needles 202 are arranged one by one at intervals, the plurality of liquid injection needles 201 are connected with the liquid mixing container 30, and the plurality of liquid discharging needles 202 are connected with the plurality of sample storage positions 102. When liquid is injected into each sample storage position 102 in the sample storage group 101 in the same row of the hybridization box 100, the plurality of liquid injection needles 201 can inject reagents into each sample storage position 102 at the same time, and the plurality of liquid discharging needles 202 can discharge waste liquid in the plurality of sample storage positions 102 in the sample storage group 101 in the same row at the same time.
[0059] After all the preset mixed reagents are prepared, the mixed liquid container 30 needs to be cleaned with a cleaning liquid. Figure 1 as well as Figure 7-Figure 9As shown, the waste liquid discharge pipeline 91 is also connected to a cleaning liquid collecting device 93 , which is funnel-shaped and is connected to the sample storage position 102 through a cleaning liquid collecting pipeline 94 alone, so as to collect the cleaning liquid.
[0060] In some embodiments, the waste liquid is toxic and is not convenient to collect with other waste liquids. Therefore, the liquid path system provided in the present application also includes a diverter device 92, which is connected to the waste liquid discharge pipeline 91 and is used to discharge the preset waste liquid, wherein the preset waste liquid is toxic waste liquid.
[0061] The present application also provides a molecular hybridization instrument, including the liquid path system in the above embodiment. For the structure and features of the liquid path system, please refer to the above embodiment and will not be described in detail here.
[0062] In summary, in the molecular hybridization instrument and liquid circuit system provided by the present application, the gating device can be automatically controlled to select the reagent supply assembly of the required component according to the components of the preset mixed reagent to be connected to the quantitative device, and the quantitative device can also be controlled according to the components of the preset mixed reagent of different types to obtain the reagent of the preset liquid amount required for the component from different reagent supply assemblies, so as to automatically calculate the reagent liquid amount and automatically obtain the reagent. Compared with the method of manual liquid preparation in the related art, the liquid can be accurately prepared to avoid reagent waste. In addition, the reagents are stored in a sealed reagent storage container, which can also avoid the problem of volatilization or even crystallization and deterioration caused by contact with air.
[0063] The above specific examples are used to illustrate the present invention, which is only used to help understand the present invention and is not intended to limit the present invention. For those skilled in the art, according to the concept of the present invention, some simple deductions, modifications or substitutions can be made.
Claims
1. A liquid circuit system, characterized in that: include: A plurality of reagent supply assemblies, wherein the plurality of reagent supply assemblies are used to provide a plurality of types of reagents; A quantitative device, used to obtain a preset amount of reagent from the reagent supply assembly; a liquid mixing container, the liquid mixing container being in communication with the quantitative device, and being used for receiving a preset liquid amount of reagent obtained by the quantitative device, and being able to mix at least two types of reagents into a preset mixed reagent; A plurality of liquid injection pipelines, the plurality of liquid injection pipelines being in communication with the liquid mixing container and being used for injecting the preset mixed reagent into a plurality of sample storage positions in the sample storage group of the hybridization box; A gating device, the gating device is connected between the plurality of the reagent supply components and the quantitative device, and is connected between the quantitative device and the liquid mixing container, the gating device is used to selectively connect the reagent supply components with the quantitative device, and connect the quantitative device with the liquid mixing container after the quantitative device obtains a preset amount of reagent; A control module, wherein the control module is electrically connected to the quantitative device and the gating device, and the control module is used to control the gating device to selectively connect different reagent supply components with the quantitative device according to the components of the preset mixed reagent, and can also control the quantitative device to obtain different preset liquid amounts of reagents from different reagent supply components according to the components of different types of preset mixed reagents.
2. The fluid path system according to claim 1, characterized in that: It also includes a cleaning liquid supply pipeline, which is used to provide cleaning liquid. The gating device is also connected between the cleaning liquid supply pipeline and the quantitative device, and is used to selectively connect the cleaning liquid supply pipeline with the quantitative device; the control module can also control the gating device to connect the cleaning liquid supply pipeline with the quantitative device after each preparation of the preset mixed reagent is completed, and control the quantitative device to obtain cleaning liquid from the cleaning liquid supply pipeline, and transport the cleaning liquid to the mixed liquid container through the quantitative device.
3. The fluid path system according to claim 2, characterized in that: The reagent supply assembly includes a plurality of first reagent supply pipelines and a plurality of second reagent supply pipelines, wherein the plurality of first reagent supply pipelines are used to connect to a first reagent supply source of a plurality of first type reagents, and the plurality of second reagent supply pipelines are used to connect to a second reagent supply source of a plurality of second type reagents; The liquid circuit system further includes a plurality of three-way solenoid valves, each of which corresponds to each of the plurality of second reagent supply pipelines. The three-way solenoid valves have a common end, a normally closed end, and a normally open end. The common end is interconnected with the gating device through the second reagent supply pipeline. The normally closed end is used to communicate with the second reagent supply source, and the normally open end is interconnected with the liquid mixing container. The three-way solenoid valve is electrically connected to the control module. The gating device is connected between a plurality of the first reagent supply pipelines and the quantitative device, and is also connected between a plurality of the second reagent supply pipelines and the quantitative device; The control module controls the gating device to selectively connect different first reagent supply pipelines to the quantitative device according to the components of the preset mixed reagent, and can also control the quantitative device to obtain different first preset liquid volumes of the first reagent from different first reagent supply pipelines according to the components of different types of preset mixed reagents; and / or, The control module controls the gating device to connect the cleaning liquid supply pipeline with the quantitative device, and after the quantitative device extracts a preset content of cleaning liquid, controls the gating device to selectively connect different second reagent supply pipelines with the quantitative device, and can control the quantitative device to inject a preset content of cleaning liquid into the second reagent supply pipeline according to the components of different types of preset mixed reagents, control the normally closed end of the three-way solenoid valve to open, control the quantitative device to work, and use the transported cleaning liquid to transport the second preset liquid amount of the second reagent to the mixed liquid container through the common end.
4. The fluid path system according to claim 3, characterized in that: The gating device includes a main body, a core body and a rotating drive assembly, the main body has a main channel, a cleaning liquid branch channel, a plurality of first branch channels and a plurality of second branch channels, the core body is rotatably connected to the main body, the core body is provided with a transition channel, one end of the transition channel is always connected to the main channel, the main channel is connected to the quantitative device, the other end of the transition channel is connected to the cleaning liquid branch channel, or a different first branch channel, or a different second branch channel; the cleaning liquid branch channel is connected to the cleaning liquid supply pipeline, the first branch channel is connected to the first reagent supply pipeline, and the second branch channel is connected to the second reagent supply pipeline; the core body is transmission-connected to the rotating drive assembly for driving the core body to rotate so as to switch the other end of the transition channel to be connected to the cleaning liquid branch channel, or a different first branch channel, or a different second branch channel.
5. The fluid path system according to claim 2, characterized in that: It also includes a cleaning liquid delivery device, which is connected between the cleaning liquid supply pipeline and the mixed liquid container. The cleaning liquid delivery device is also electrically connected to the control module. The control module can also control the cleaning liquid delivery device to deliver the cleaning liquid to the mixed liquid container after completing the preparation of all preset mixed reagents.
6. The fluid circuit system according to claim 1, characterized in that: It also includes a mixing device, which is communicated with the mixing liquid container and electrically connected to the control module. The control module is used to mix at least two types of reagents after the quantitative device provides at least two reagents required for the preset mixed reagent.
7. The fluid circuit system according to claim 6, characterized in that: It also includes a heating device, which is connected to the mixed liquid container and electrically connected to the control module. The control module is used to control the heating device to heat the mixed liquid container to a preset temperature according to the preset mixed reagent that needs to be preheated.
8. The fluid circuit system according to claim 1, characterized in that: The device also comprises a waste liquid discharge pipeline, which is used to discharge the waste liquid in the hybridization box.
9. The fluid circuit system according to claim 8, characterized in that: It also includes a diverter device, which is connected to the waste liquid discharge pipeline and is used to discharge the preset waste liquid.
10. A molecular hybridization instrument, characterized in that: Comprising the fluid circuit system as described in any one of claims 1-9.
Citation Information
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