CN118259039A - Reagent dispensing device, reagent dispensing method, and sample analyzer - Google Patents
Reagent dispensing device, reagent dispensing method, and sample analyzer Download PDFInfo
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- CN118259039A CN118259039A CN202311835153.3A CN202311835153A CN118259039A CN 118259039 A CN118259039 A CN 118259039A CN 202311835153 A CN202311835153 A CN 202311835153A CN 118259039 A CN118259039 A CN 118259039A
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- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 1158
- 238000000034 method Methods 0.000 title claims abstract description 26
- 239000007788 liquid Substances 0.000 claims abstract description 169
- 238000006243 chemical reaction Methods 0.000 claims abstract description 118
- 238000007599 discharging Methods 0.000 claims abstract description 42
- 238000004140 cleaning Methods 0.000 claims description 153
- 239000012530 fluid Substances 0.000 claims description 51
- 150000007523 nucleic acids Chemical class 0.000 claims description 40
- 102000039446 nucleic acids Human genes 0.000 claims description 40
- 108020004707 nucleic acids Proteins 0.000 claims description 40
- 238000005406 washing Methods 0.000 claims description 30
- 238000000605 extraction Methods 0.000 claims description 19
- 238000001514 detection method Methods 0.000 claims description 17
- 230000003321 amplification Effects 0.000 claims description 15
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 15
- 239000006166 lysate Substances 0.000 claims description 14
- 239000011259 mixed solution Substances 0.000 claims description 14
- 108010067770 Endopeptidase K Proteins 0.000 claims description 13
- 239000011324 bead Substances 0.000 claims description 12
- 239000012086 standard solution Substances 0.000 claims description 11
- 230000033001 locomotion Effects 0.000 claims description 10
- 238000010926 purge Methods 0.000 claims 3
- 230000007246 mechanism Effects 0.000 description 24
- 238000010586 diagram Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 239000012807 PCR reagent Substances 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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Abstract
The embodiment of the application provides a reagent dispensing device, a reagent dispensing method and a sample analyzer, wherein the sample analyzer comprises the reagent dispensing device and a control component: the reagent dispensing device comprises a reagent needle and a liquid path supporting component; the reagent needle is used for sucking and discharging the reagent, the liquid path support component is connected with the reagent needle and is used for providing power for sucking and discharging the reagent to the reagent needle; the control assembly is used for: controlling the liquid path support assembly to enable the same reagent needle to absorb the first air column, and controlling the liquid path support assembly to enable the reagent needle to absorb a plurality of reagents in the reagent container after the first air column is absorbed; the control liquid path support component enables the reagent needle to discharge the sucked multiple reagents to the same first reaction container. The efficiency of reagent dispensing and the utilization rate of the reagent can be improved.
Description
Technical Field
The application relates to the technical field of medical equipment, in particular to a reagent dispensing device, a reagent dispensing method and a sample analyzer.
Background
In order to prevent cross contamination between reagents when performing reagent dispensing, a related art needs to replace a disposable TIP (TIP) after each separate reagent is added, increasing consumable cost and replacing the disposable TIP reduces efficiency of reagent dispensing. When a reusable liquid suction needle such as a steel needle is used, one reagent is sucked and discharged firstly, and the other reagent is sucked after cleaning, so that the sucked reagent can be diluted by liquid in the liquid suction needle, and the reagent dispensing accuracy is reduced; although the dilution ratio can be reduced and the accuracy can be improved by the multi-liquid absorption amount, the waste of the reagent is caused.
Disclosure of Invention
The application provides a reagent dispensing device, a reagent dispensing method and a sample analyzer, which can improve the reagent dispensing efficiency and the reagent utilization rate.
In a first aspect, an embodiment of the present application provides a sample analyzer, including:
a reagent storage device for housing a reagent container;
a reagent dispensing device for dispensing a plurality of extraction reagents in the reagent container to a first reaction container;
a sample dispensing device for dispensing a sample to the first reaction vessel, the sample and the extraction reagent forming a first mixed solution;
a nucleic acid extraction device for extracting nucleic acid from the first mixed solution in the first reaction vessel; the sample dispensing device is further used for transferring the nucleic acid in the first reaction container to a second reaction container, and the nucleic acid and the amplification reagent in the second reaction container form a second mixed solution;
An amplification device for amplifying nucleic acids in the second mixed solution;
A detection device for detecting the amplified nucleic acid;
the reagent dispensing device includes:
a reagent needle for sucking up a reagent and discharging the reagent;
A liquid path support assembly connected to the reagent needle and for providing motive power for sucking and discharging a reagent to the reagent needle through a liquid;
the sample analyzer further comprises a control assembly for:
Controlling the liquid path supporting component to enable the same reagent needle to absorb a first air column;
controlling the liquid path support assembly after the first air column is sucked so that the reagent needle sequentially sucks a plurality of reagents in the reagent container;
Controlling the liquid path support assembly to enable the reagent needle to discharge the sucked multiple reagents to the same first reaction container.
In a second aspect, an embodiment of the present application provides a reagent dispensing device, including:
a reagent needle for sucking up a reagent and discharging the reagent;
A fluid path support assembly connected to the reagent needle and adapted to provide motive power for sucking and discharging a reagent to the reagent needle;
a control assembly for:
Controlling the liquid path supporting component to enable the same reagent needle to absorb a first air column;
Controlling the liquid path support assembly after the first air column is sucked so that the reagent needle sequentially sucks a plurality of reagents in the reagent container; and
And controlling the liquid path supporting component to enable the reagent needle to discharge the sucked multiple reagents into the same reaction container.
In a third aspect, an embodiment of the present application provides a reagent dispensing method, including:
Sucking a first air column through a reagent needle;
sequentially sucking a plurality of reagents through the same reagent needle after sucking the first air column;
The plurality of reagents sucked up are discharged to the same reaction vessel through the reagent needle.
The embodiment of the application provides a reagent dispensing device, a reagent dispensing method and a sample analyzer, which can dispense a plurality of reagents in one reagent dispensing flow; compared with the method that each time one reagent is sucked, the sucked reagent is distributed to the first reaction container, so that the reagent distribution efficiency can be improved; the reagent discharged later can bring out the part of the reagent discharged earlier remained in the reagent needle to the first reaction vessel, and the utilization rate of the reagent can be improved.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure of embodiments of the application.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a sample analyzer according to an embodiment of the present application;
FIG. 2 is a schematic block diagram of a sample analyzer in one embodiment;
FIG. 3 is a schematic structural view of a reagent dispensing device according to an embodiment of the present application;
FIG. 4 is a schematic illustration of a reagent dispensing device for dispensing reagent in one embodiment;
FIG. 5 is a schematic view of a reagent dispensing device according to another embodiment;
FIG. 6 is a schematic view of a reagent dispensing device according to still another embodiment;
FIG. 7 is a schematic diagram of a cleaning assembly in one embodiment;
FIG. 8 is a schematic diagram of the structure of a cleaning assembly and a fluid path support assembly in one embodiment;
fig. 9 is a schematic flow chart of a reagent dispensing method according to an embodiment of the present application.
Reference numerals illustrate: 10. a reagent storage device; 100. a reagent dispensing device; 110. a reagent needle; 130. a fluid path support assembly; 131. a reagent syringe; 132. a reagent line; 133. a needle blocking sensor; 140. a control assembly; 150. a drive assembly;
200. A sample dispensing device; 300. a nucleic acid extraction device; 410. an amplification device; 420. a detection device; 500. a control assembly; 600. cleaning the assembly; 601. cleaning the outer wall of the injector; 602. a first three-way valve; 603. a cleaning pool; 604. a negative pressure generating mechanism; 6041. a diaphragm pump; 6042. a vacuum tank; 6043. an electromagnetic valve; 605. cleaning the inner wall of the injector; 606. a second three-way valve;
A. A reagent container; a1, a first reagent; a2, a second reagent; a3, a third reagent; a4, a fourth reagent; E. a first reaction vessel; F. a second reaction vessel; c1, system liquid; x, a first air column; Y1-Y4, a second air column;
10. a functional module; 20. an input module; 30. a display module; 40. a memory; 50. a processor.
Detailed Description
The following description of the embodiments of the present application will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are some, but not all embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
The flow diagrams depicted in the figures are merely illustrative and not necessarily all of the elements and operations/steps are included or performed in the order described. For example, some operations/steps may be further divided, combined, or partially combined, so that the order of actual execution may be changed according to actual situations.
Some embodiments of the present application are described in detail below with reference to the accompanying drawings. The following embodiments and features of the embodiments may be combined with each other without conflict.
Referring to fig. 1, fig. 1 is a schematic block diagram of a sample analyzer according to an embodiment of the application. In some embodiments, the sample analyzer includes, but is not limited to, at least one of: molecular diagnostic apparatus, biochemical analyzer, immunoassay analyzer. The molecular diagnostic instrument is, for example, a nucleic acid extractor or a nucleic acid detector.
For convenience of explanation, a sample analyzer will be mainly described as a molecular diagnostic apparatus. Illustratively, the sample analyzer is a nucleic acid detection device.
Before explaining the present invention in detail, a description will be given of the structure of a sample analyzer in some embodiments.
Referring to fig. 2, an embodiment discloses a sample analyzer, which includes at least one functional module 10 (or one or more functional modules 10), an input module 20, a display module 30, a memory 40, and a processor 50, which are described below.
Each functional module 10 is used for performing at least one function required in the sample analysis process, and the functional modules 10 cooperate together to perform the sample analysis to obtain a sample analysis result. As some examples of the functional module 10, the functional module 10 may include a sample management part, a sample dispensing mechanism, a reagent management part, a reagent dispensing mechanism, a mixing mechanism, a nucleic acid extraction part, a PCR (Polymerase Chain Reaction ) detection part, and the like.
The sample management component is used for bearing and managing samples.
The sample dispensing mechanism is used for injecting a sample into the reaction cup. For example, the sample dispensing mechanism may comprise a sample needle that is moved in two or three dimensions by a two or three dimensional drive mechanism so that the sample needle can be moved to aspirate a sample carried by the sample component and to move to a cuvette to be loaded and to discharge the sample to the cuvette.
The reagent management component is used for bearing and managing the reagent. In one embodiment, the reagent component may be a reagent disk, where the reagent disk is provided in a disk-shaped structure and has a plurality of positions for carrying reagent containers, and the reagent component can rotate and drive the reagent containers carried by the reagent component to rotate, so as to rotate the reagent containers to a specific position, for example, a position where the reagent is sucked by the reagent dispensing mechanism.
The reagent dispensing mechanism is used for sucking the reagent and discharging the reagent into a reaction cup to be added with the reagent. In one embodiment, the reagent dispensing mechanism may include a reagent needle that is moved in two or three dimensions by a two or three dimensional drive mechanism so that the reagent needle can be moved to aspirate reagent carried by the reagent component and to move to a cuvette to be filled with reagent and to discharge reagent to the cuvette. For example, the reagent dispensing device according to the embodiment of the present application may include the reagent dispensing mechanism, which is not limited thereto.
The sample dispensing mechanism and the reagent dispensing mechanism may be integrated into a single dispensing mechanism for injecting the sample and/or reagent.
The mixing mechanism is used for uniformly mixing the reaction liquid which needs to be uniformly mixed in the reaction cup. The number of mixing mechanisms may be one or more.
The nucleic acid extraction means is used for extracting nucleic acid in the reaction solution.
The PCR detection unit is used for performing PCR amplification detection on the extracted nucleic acid, for example, the PCR detection unit includes an amplification device 410 and a detection device 420, the amplification device 410 is used for amplifying the nucleic acid in the second mixed solution, and the detection device 420 is used for detecting the amplified nucleic acid.
The foregoing is illustrative of some of the functional modules 10 and the following continues with a description of other components and structures in the sample analyzer.
The input module 20 is for receiving input from a user. Typically, the input module 20 may be a mouse, a keyboard, etc., and in some cases may also be a touch display screen, which brings about functions for a user to input and display content, so that in this example the input module 20 and the display module 30 are integrated. Of course, in some examples, the input module 20 may even be a voice input device or the like that brings up recognition voice.
The display module 30 may be used to display information. In some embodiments, the sample analyzer itself may incorporate a display module, and in some embodiments, the sample analyzer may be connected to a computer device (e.g., a computer) for displaying information via a display unit (e.g., a display screen) of the computer device, which falls within the scope of the display module 30 herein defined and protected.
It should be understood that the sample analyzer depicted in fig. 2 is only a specific example, and is not limited to the reagent dispensing device and the sample analyzer according to the embodiments of the present application, and the sample analyzer according to the embodiments of the present application may be implemented in other specific manners. For example, in other implementations, the sample analyzer may have more or fewer components.
For convenience of explanation, the sample analyzer is mainly used as a molecular diagnostic device, and the reagent dispensing device is used as a reagent dispensing device in the molecular diagnostic device.
As shown in fig. 1, the sample analyzer includes: the reagent storage device 10, the reagent dispensing device 100, the sample dispensing device 200, the nucleic acid extracting apparatus 300, the amplification device 410, the detection device 420, and the control unit 500.
The reagent storage device 10 is used for accommodating a reagent container A; for example, the reagent storage device 10 is used to house one or more reagent containers a, which may house different reagents. For example, the reagent container a contains an extraction reagent for a plurality of nucleic acids.
The reagent dispensing device 100 is used to dispense a plurality of extraction reagents in the reagent vessel a to the first reaction vessel E.
The sample dispensing device 200 is used for dispensing a sample to the first reaction container E, the sample and the extraction reagent forming a first mixed solution.
The nucleic acid isolation apparatus 300 is used for nucleic acid isolation from the first mixed solution in the first reaction vessel E. For example, the nucleic acid extraction apparatus 300 extracts nucleic acids by, for example, a magnetic bead purification method, but is not limited to this, and nucleic acids may be extracted by, for example, a column extraction method, a solution extraction method, or the like.
The sample dispensing device 200 is also used to transfer nucleic acids in a first reaction vessel E to a second reaction vessel F, such as a PCR (Polymerase Chain Reaction ) tube; the nucleic acid and amplification reagents (such as PCR reagents) in the second reaction vessel F form a second mixture; optionally, the second reaction vessel F is pre-filled with the amplification reagents, or the sample dispensing device 200 or other priming device injects the amplification reagents into the second reaction vessel F.
The amplification device 410 is used for amplifying the nucleic acid in the second mixed solution, and the detection device 420 is used for detecting the amplified nucleic acid.
In some embodiments, the detection procedure of the molecular diagnostic analyzer comprises:
The reagent dispensing device 100 dispenses four kinds of extraction reagents, such as a first reagent A1, a second reagent A2, a third reagent A3, and a fourth reagent A4, to the first reaction container E;
adding a sample liquid to the first reaction vessel E;
Dispatching the first reaction vessel E to the nucleic acid extraction device 300 for nucleic acid extraction;
Adding PCR reagent into the second reaction container F;
adding the nucleic acid extracted in the first reaction vessel E to the second reaction vessel F;
The second reaction vessel F is dispatched to the amplification apparatus 410 for amplification and detection by the detection apparatus 420.
Fig. 3 is a schematic structural diagram of a reagent dispensing device 100 according to an embodiment of the present application. As shown in fig. 3, a reagent dispensing device 100 according to an embodiment of the present application includes: a reagent needle 110, a fluid path support assembly 130.
Wherein the reagent needle 110 is used for sucking up and discharging a reagent. Alternatively, the reagent needle 110 is a reusable reagent needle 110, such as a steel needle, which can reduce consumable part (TIP) consumption; of course, the material of the reagent needle 110 may not be limited.
Referring to fig. 4 in conjunction with fig. 3, the reagent dispensing device 100 may further comprise a drive assembly 150, the drive assembly 150 being configured to drive the reagent needle 110 and/or the reagent vessel a such that the reagent needle 110 is positioned in the reagent vessel a for pipetting; the drive assembly 150 is also used to drive the reagent needle 110 and/or the first reaction vessel E such that the reagent needle 110 is positioned in the first reaction vessel E for draining.
Optionally, the drive assembly 150 is used to drive the reagent needle 110 between the reagent storage device 10 and the location of the first reaction vessel E. For example, the drive assembly 150 comprises a mechanism that can perform a two-dimensional movement or a three-dimensional movement, which carries the reagent needle 110, ensuring that the reagent needle 110 can reach the reagent vessel a or the first reaction vessel E; the driving assembly 150 may also drive the reagent needle 110 to move downward above the reagent vessel a so that the needle opening of the reagent needle 110 is located below the liquid surface of the reagent vessel a for pipetting; the driving assembly 150 may also drive the reagent needle 110 to move downward above the first reaction container E such that the needle opening of the reagent needle 110 is located in the first reaction container E, such as the bottom of the first reaction container E, for draining. Of course, not limited thereto, alternatively, the driving assembly 150 may be used to drive the reagent vessel a or the first reaction vessel E to move below the reagent needle 110, and may also drive the reagent vessel a or the first reaction vessel E to move in a direction below the reagent needle 110, so that the needle opening of the reagent needle 110 is located below the liquid surface of the reagent vessel a or in the first reaction vessel E, such as the bottom of the first reaction vessel E.
For ease of description, embodiments of the present application will be described primarily with reference to the drive assembly 150 driving the reagent needle 110 to move.
The liquid path support assembly 130 is connected to the reagent needle 110 and serves to provide power for sucking and discharging the reagent to the reagent needle 110; for example, the fluid path support assembly 130 is used to provide motive force for aspirating and discharging reagents through a fluid, such as system fluid C1, to the reagent needle 110. For example, as shown in fig. 5 and 6, the liquid path support assembly 130 includes a reagent syringe 131, the reagent syringe 131 may provide negative pressure to the reagent needle 110 to suck the reagent by the reagent needle 110, and the reagent syringe 131 may also provide positive pressure to the reagent needle 110 to discharge the sucked reagent by the reagent needle 110.
The sample analyzer further includes a control assembly 500. As shown in fig. 3, the reagent dispensing device 100 further includes a control unit 140, and the control unit 140 may be used as the control unit 500 of the sample analyzer, which is not limited thereto.
Referring to fig. 5 and 6 in conjunction with fig. 4, the control assembly 500 is configured to: controlling the fluid path support assembly 130 to cause the same reagent needle 110 to draw a first column of air X; controlling the liquid path support assembly 130 to make the reagent needle 110 sequentially suck a plurality of reagents in the reagent container a after sucking the first air column X; the control fluid path support assembly 130 causes the reagent needle 110 to discharge the sucked plurality of reagents to the same first reaction container E.
In some embodiments, as shown in fig. 4, the control assembly 500 is further configured to: the liquid path support unit 130 is controlled to suck the first air column X from the same reagent needle 110 before the driving unit 150 drives the reagent needle 110 to move toward the reagent container a, or during the driving unit 150 drives the reagent needle 110 to move toward the reagent container a, or after the driving unit 150 drives the reagent needle 110 to move toward the reagent container a. That is, the liquid path support assembly 130 is controlled after the reagent needle 110 sucks the first air column X so that the reagent needle 110 sequentially sucks a plurality of reagents in the reagent vessel a.
For example, as shown in fig. 5, by sucking the first air column X before sucking the plurality of reagents, the sucked reagents are isolated from the system liquid C1 in the liquid path support member 130 by the first air column X.
For example, the reagent needle 110 sequentially sucks 2 to 5 reagents in the reagent container a, but the number of kinds of the plurality of reagents is not limited thereto. Referring to fig. 4 to 6, for convenience of description, the embodiment of the application mainly uses the first target reagent and at least one second target reagent for sucking. For example, the first target reagent comprises a first reagent A1, the at least one second target reagent may comprise at least one of a second reagent A2, a third reagent A3 and a fourth reagent A4, e.g. the reagent needle 110 aspirates each reagent in the respective reagent containers a of the four reagents A1, A2, A3, A4.
After the reagent needle 110 suctions the plurality of reagents, controlling the driving assembly 150 to position the reagent needle 110 in the first reaction container E, and controlling the liquid path supporting assembly 130 to discharge the suctioned plurality of reagents together by the reagent needle 110 into the first reaction container E, for example, sequentially discharging the fourth reagent A4, the third reagent A3, the second reagent A2, and the first reagent A1 into the first reaction container E; the first discharged reagent (e.g., the second target reagent such as the second reagent A2) may sometimes remain in the reagent needle 110, and the later discharged reagent (e.g., the first target reagent such as the first reagent A1) may discharge the remaining reagent in the reagent needle 110 together into the first reaction vessel E, so as to clean the interior of the reagent needle 110, and ensure that the later sucked reagent may be completely discharged into the first reaction vessel E. It should be noted that the sucked first reagent A1 may be completely discharged into the first reaction vessel E, or may be partially discharged into the first reaction vessel E, for example, the remaining first reagent A1 may be discharged to a place other than the first reaction vessel E to at least achieve a cleaning effect on the inner wall of the reagent needle 110.
Dispensing multiple reagents in one reagent dispensing flow may be accomplished by sequentially drawing multiple reagents through the same reagent needle 110, and then discharging the multiple reagents into the same discharge container; compared with the method that each time one reagent is sucked, the sucked reagent is dispensed to the first reaction container E, the time consumption for driving the reagent needle 110 to move can be reduced, and the reagent dispensing efficiency is improved.
In some embodiments, when the reagent needle 110 discharges the sucked plurality of reagents to the same first reaction container E, the discharge amount of the remaining reagents except for the first sucked one is equal to the suction amount; or the discharge amount of the plurality of reagents is equal to the suction amount. For example, when the reagent needle 110 discharges the plurality of reagents sucked into the same first reaction container E, the discharging sequence of the plurality of reagents is opposite to the sucking sequence, for example, the fourth reagent A4, the third reagent A3, and the second reagent A2 are sequentially discharged, and then the first reagent A1 is discharged, where the reagent discharged later can bring out the part of the reagent discharged earlier that remains in the reagent needle 110 and discharge the reagent into the first reaction container E, for example, the discharge amount of the fourth reagent A4, the third reagent A3, and the second reagent A2 can be made equal to the sucking amount, so that the influence of the reagent being diluted can be reduced or eliminated, and the reagent dispensing accuracy can be improved. Compared with the scheme of ensuring the accuracy and the dilution rate of reagent dispensing through multiple liquid absorption amounts, the embodiment of the application can also prevent the waste of reagents.
In some embodiments, the first reagent that is aspirated when the reagent needle 110 aspirates the plurality of reagents is a first target reagent. The discharge amount of the first target reagent discharged from the reagent needle 110 to the first reaction container E is greater than the suction amount of at least one second target reagent sucked after the first target reagent; for example, the discharge amount of the first reagent A1 discharged from the reagent needle 110 to the first reaction container E is larger than the suction amount of at least one second target reagent among the second reagent A2, the third reagent A3, and the fourth reagent A4. Alternatively, the discharge amount of the first target reagent discharged from the reagent needle 110 to the first reaction container E is greater than or equal to the sum of the suction amounts of the various second target reagents sucked later, e.g., the discharge amount of the first reagent A1 discharged to the first reaction container E is 3 times to 15 times, e.g., 9 times, the sum of the suction amounts of the second reagent A2, the third reagent A3, and the fourth reagent A4. More of the second target reagent remaining in the reagent needle 110 can be carried into the first reaction container E by more of the first target reagent, and the accuracy of reagent dispensing is higher.
Illustratively, when the reagent needle 110 aspirates the plurality of reagents, the first aspirated reagent is a first target reagent that aspirates more than the at least one second target reagent that is aspirated later. Alternatively, when the reagent needle 110 sucks the plurality of reagents, the suction amount of the first sucked reagent is greater than or equal to the sum of suction amounts of the respective reagents sucked later, such as the suction amount of the first reagent A1 is greater than or equal to the sum of suction amounts of the second reagent A2, the third reagent A3, and the fourth reagent A4, and for example, the suction amount of the first reagent A1 is 3 times to 15 times, such as 9 times, the sum of suction amounts of the second reagent A2, the third reagent A3, and the fourth reagent A4. The first reagent A1 may be discharged to the first reaction vessel E in its entirety or may be partially discharged to the first reaction vessel E.
Optionally, the first target reagent such as the first reagent A1 which needs to be discharged into the first reaction vessel E has a large demand, and/or the first target reagent such as the first reagent A1 has a lower cost than at least one second target reagent which is to be sucked later; the second target reagent such as the second reagent A2, the third reagent A3 and the fourth reagent A4 which have smaller demand and higher cost do not need more liquid absorption; and more second target reagent remained in the reagent needle 110 can be brought into the first reaction container E by more first target reagent, so that the reagent dispensing accuracy is higher; the influence of the residue on the inner wall on the sample adding accuracy, repeatability and dilution rate of the second reagent A2, the third reagent A3 and the fourth reagent A4 can be basically eliminated on the basis of less reagent consumption.
In some embodiments, referring to fig. 6, after each time the reagent needle 110 draws one reagent, the control assembly 500 is further configured to control the fluid path support assembly 130 to draw the reagent needle 110 into a second column of air Y, such as second column of air Y1-second column of air Y4. As shown in fig. 6, after the reagent needle 110 suctions the first target reagent, such as the first reagent A1, the liquid path support assembly 130 is controlled to cause the reagent needle 110 to suction the second air column Y1, after which the reagent needle 110 suctions the second target reagent, such as the second reagent A2.
For example, referring to fig. 4, when the reagent needle 110 sequentially sucks the plurality of reagents, the first target reagent and the second target reagent are sequentially sucked, such as the first reagent A1 and the second reagent A2 are sequentially sucked.
In some embodiments, the controlling the liquid path support assembly 130 to sequentially aspirate the plurality of reagents in the reagent vessel a after aspirating the first column of air X includes: controlling the fluid path support assembly 130 to cause the reagent needle 110 to aspirate a first target reagent, such as first reagent A1; after the reagent needle 110 suctions the first target reagent, controlling the liquid path support assembly 130 to cause the reagent needle 110 to suction the second air column Y1; the control fluid path support assembly 130 causes the reagent needle 110 to aspirate at least one second target reagent, such as at least the second reagent A2, after aspirating the second column of air.
By controlling the liquid path support unit 130 so that the reagent needle 110 sucks the second air column Y1 after the reagent needle 110 sucks the first reagent A1, the sucked first reagent A1 can be prevented from being thrown out from the needle opening of the reagent needle 110 when the reagent needle 110 moves toward the reagent container a of the second reagent A2.
Wherein controlling the fluid path support assembly 130 to cause the reagent needle 110 to aspirate the first target reagent may include: the control driving assembly 150 drives the reagent needle 110 to move to the reagent container a of the first reagent A1; after the reagent needle 110 moves to the reagent container a of the first reagent A1, the control fluid path support assembly 130 causes the reagent needle 110 to suck the first reagent A1; after the reagent needle 110 suctions the first reagent A1, the drive assembly 150 is controlled to move the reagent needle 110 away from the liquid surface of the first reagent A1. Controlling the fluid circuit support assembly 130 to cause the reagent needle 110 to aspirate at least one second target reagent may include: the control driving assembly 150 moves the reagent needle 110 to a second target reagent, such as a reagent container a of a second reagent A2, and the control liquid path supporting assembly 130 causes the reagent needle 110 to suck the second reagent A2; after the reagent needle 110 suctions the second reagent A2, the drive assembly 150 is controlled to move the reagent needle 110 away from the liquid surface of the second reagent A2.
For example, referring to fig. 4, the second target reagent includes at least two kinds, such as a second reagent A2, a third reagent A3 and a fourth reagent A4. The liquid path support assembly 130 may be controlled to cause the reagent needle 110 to aspirate a second column of air after each aspiration of one of the second target reagents; for example, the second air column Y2 and the third reagent A3 are sucked after the second reagent A2 is sucked, the second air column Y3 and the fourth reagent A4 are sucked after the third reagent A3 is sucked, and the second air column Y4 may be sucked after the fourth reagent A4 is sucked.
Illustratively, after each draw of one second target reagent by reagent needle 110, a second column of air Y is drawn; and after the second air column Y is sucked, the reagent container a moved to the next second target reagent or the first reaction container E is moved, so that the reagent which the reagent needle 110 has sucked can be prevented from being thrown out of the needle opening of the reagent needle 110 during the movement of the reagent needle 110.
After the reagent needle 110 sucks the fourth reagent A4, controlling the liquid path support assembly 130 to make the reagent needle 110 suck the second air column Y4 at the reagent container a, and then controlling the driving assembly 150 to move to the first reaction container E, controlling the liquid path support assembly 130 to make the reagent needle 110 discharge the sucked plurality of reagents to the same first reaction container E; by sucking the second air column Y4, the sucked reagent can be prevented from being thrown out from the mouth of the reagent needle 110 when the reagent needle 110 moves toward the first reaction container E.
It should be noted that, as shown in fig. 5, the reagent needle 110 according to the embodiment of the present application may not suck the second air column Y. Since the discharge amounts of the fourth reagent A4, the third reagent A3, and the second reagent A2 are equal to the respective suction amounts, and the fourth reagent A4, the third reagent A3, the second reagent A2, and the first reagent A1 are all discharged into the same first reaction vessel E, the embodiment of the present application can isolate different reagents without passing through an air column; it will be appreciated that the reagent needle 110 of the present embodiment draws the second column of air Y primarily to prevent reagent from being thrown out during movement of the reagent needle 110.
In some embodiments, as shown in fig. 5 and 6, the fluid path support assembly 130 includes a reagent syringe 131, the reagent syringe 131 having a volume greater than or equal to the sum of the volumes of reagent and air column aspirated by the reagent needle 110; by using a larger volume of reagent injector 131, the liquid suction requirements of the plurality of reagents are guaranteed, for example, the volume of the reagent injector 131 is 1000ul (microliter).
Illustratively, as shown in fig. 5 and 6, the fluid path support assembly 130 includes a reagent syringe 131 and a reagent line 132, the reagent needle 110 is connected to the reagent syringe 131 through the reagent line 132, and the reagent syringe 131 supplies negative or positive pressure to the reagent needle 110 through the reagent line 132.
For example, the sum of the volume of the reagent needle 110 and the volume of the reagent line 132 is greater than the sum of the volumes of the reagent and the air column sucked by the reagent needle 110, such as the sum of the volumes of the first air column X, the first reagent A1, the second air column Y1, the second reagent A2, the second air column Y2, the third reagent A3, the second air column Y3, the fourth reagent A4, and the second air column Y4 in fig. 6, to ensure that the sucked reagent and air column do not enter the reagent injector 131. For example, the volume of the reagent injector 131 is 1000ul, the volume of the reagent needle 110 is 220ul, and the volume of the reagent line 132 is at least 800ul. When the sum of the volume of the reagent needle 110 and the volume of the reagent line 132 is larger than the volume of the reagent syringe 131, the reagent and the air column sucked up by the reagent syringe 131 can be prevented from entering the reagent syringe 131.
Optionally, the volume of the reagent needle 110 is less than the sum of the volumes of reagent and air column aspirated by the reagent needle 110; for example, when the sum of the volume of the reagent needle 110 and the volume of the reagent line 132 is greater than the sum of the volumes of the reagent and the column of air drawn by the reagent needle 110, and the volume of the reagent needle 110 is less than the sum of the volumes of the reagent and the column of air drawn by the reagent needle 110, as shown in fig. 6, the reagent line 132 may be used to hold a portion of the reagent and/or the column of air drawn by the reagent needle 110, such as to hold a portion of the first reagent A1; the reagent needle 110 may be a smaller volume reagent needle 110, such as a 220ul volume reagent needle 110; the smaller volume reagent needle 110 typically has a higher accuracy, e.g., the accuracy of the 220ul volume reagent needle 110 is up to 0.1ul, thereby improving the accuracy of the reagent injection. Of course, also without limitation, the volume of the reagent needle 110 may be greater than the sum of the volumes of reagent and air column aspirated by the reagent needle 110; depending on the amount of reagent required, the reagent aspirated by the reagent needle 110 may not enter the reagent line 132.
In some embodiments, referring to fig. 7, the sample analyzer further includes a cleaning assembly 600, where the cleaning assembly 600 is used to clean the reagent needle 110 and optionally dry the reagent needle 110. The cleaning assembly 600 is capable of providing a cleaning fluid to the reagent needle 110 to clean the reagent needle 110, although not limited thereto, and the cleaning fluid may be provided to the cleaning assembly 600 by the reagent needle 110, for example.
Optionally, after the reagent needle 110 sucks at least one reagent of the plurality of reagents, the outer wall of the reagent needle 110 may be cleaned by the cleaning assembly 600, and the outer wall of the reagent needle 110 may be dried after cleaning. Illustratively, when the reagent needle 110 sequentially aspirates the plurality of reagents, the first target reagent, e.g., including the first reagent A1, and the second target reagent, e.g., including the second reagent A2 and the third reagent A3, are sequentially aspirated.
Illustratively, as shown in FIG. 6, after the reagent needle 110 aspirates the first target reagent (e.g., the first reagent A1) and the second column of air Y1 and before aspirating the second target reagent (e.g., the second reagent A2), the drive assembly 150 may be controlled to move the reagent needle 110 to the washing assembly 600, and the washing assembly 600 may be controlled to wash the outer wall of the reagent needle 110, and the washing assembly 600 may be controlled to dry the reagent needle 110 after washing the outer wall of the reagent needle 110.
For example, as shown in fig. 6, after the reagent needle 110 suctions one second target reagent and the second air column and before suctioning the other second target reagent, the driving assembly 150 may be controlled to move the reagent needle 110 to the washing assembly 600, and the washing assembly 600 may be controlled to wash and dry the outer wall of the reagent needle 110.
For example, the control assembly 500 is further used for controlling the liquid path support assembly 130 to enable the reagent needle 110 to suck the second air column Y2 after the reagent needle 110 sucks the second reagent A2, controlling the driving assembly 150 to enable the reagent needle 110 to move to the cleaning assembly 600 after the reagent needle 110 sucks the second air column Y2 and before the third reagent A3 is sucked, and controlling the cleaning assembly 600 to clean and dry the outer wall of the reagent needle 110. The second reagent A2 remaining on the outer wall of the reagent needle 110 can be prevented from contaminating the third reagent A3 in the reagent container a when the third reagent A3 is sucked.
For example, after the reagent needle 110 suctions the last second target reagent and the second air column and before discharging the suctioned plurality of reagents to the same first reaction vessel E, the driving assembly 150 may be controlled to move the reagent needle 110 to the washing assembly 600, and the washing assembly 600 may be controlled to wash and dry the outer wall of the reagent needle 110. The reagent remaining on the outer wall of the reagent needle 110 when discharging the liquid to the first reaction container E can also be prevented from entering the first reaction container E by cleaning the outer wall after the last reagent is sucked.
Optionally, the second target reagent includes at least two target reagents, and the second target reagent includes a first type reagent and a second type reagent, the first type reagent has higher adsorptivity to the reagent needle 110 than the second type reagent, and the reagent needle 110 sucks the first type reagent before sucking the second type reagent when sucking the second target reagent. Wherein the first type of reagent comprises, for example, a second reagent A2, and the second type of reagent comprises, for example, a third reagent A3 and/or a fourth reagent A4. For example, the first reagent A1 is a lysate, the second reagent A2 is a magnetic bead, the third reagent A3 is an internal standard solution, and the fourth reagent A4 is proteinase K. For example, the liquid film thickness of the second reagent A2 on the outer wall of the reagent needle 110 after the reagent needle 110 is separated from the liquid surface of the second reagent A2 is larger than the liquid film thickness on the outer wall of the reagent needle 110 after the liquid surface of the first reagent A1 or the third reagent A3 is separated.
Illustratively, during the process of sucking the second target reagent by the reagent needle 110, the control component 140 is further configured to control the cleaning component 600 to clean the reagent needle 110 after the reagent needle 110 sucks the first type reagent, and control the liquid path support component 130 to make the reagent needle 110 suck the second type reagent in the second target reagent after the reagent needle 110 is cleaned. For example, after the reagent needle 110 sucks the second reagent A2, the driving assembly 150 is controlled to drive the reagent needle 110 to move to the cleaning assembly 600, and the cleaning assembly 600 is controlled to clean the reagent needle 110. By cleaning the outer wall of the reagent needle 110 after sucking the reagent having high adsorptivity, contamination of the reagent to be sucked later by the reagent remaining on the outer wall can be prevented. Alternatively, the outer wall of the reagent needle 110 may be cleaned in the middle when the contamination of the reagent sucked first to the reagent sucked later is great.
Optionally, the embodiments of the present application may further reduce the number of times of cleaning the outer wall of the reagent needle 110 when the plurality of reagents are sucked, and reduce the time consumed for cleaning and the consumption of cleaning liquid, for example, when the sucked reagent (such as the third reagent A3) has weak adsorptivity to the reagent needle 110, the outer wall of the reagent needle 110 may not be cleaned after the reagent is sucked.
Compared with the scheme that the inner wall and the outer wall of the reagent needle 110 are cleaned before sucking another reagent and discharging one reagent, the method and the device prevent the reagent sucked after the reagent sucked and discharged earlier from being polluted, the embodiment of the application can reduce the time consumption of cleaning and the consumption of cleaning fluid because the cleaning of the inside of the reagent needle 110 is not required when sucking the plurality of reagents.
In some embodiments, the performance of the second reagent A2 and the third reagent A3 is affected when the first reagent A1 is mixed with the second reagent A2 and the third reagent A3, the performance of the second reagent A2 and the third reagent A3 is affected when the fourth reagent A4 is mixed with the second reagent A2 and the third reagent A3, the adsorptivity of the second reagent A2 to the reagent needle 110 is stronger than that of the first reagent A1, the third reagent A3 and the fourth reagent A4, and the influence of the reagent residues on the outer wall of the reagent needle 110 on the performance of the other reagents is reduced or eliminated by sucking the first reagent A1, the second reagent A2, the third reagent A3 and the fourth reagent A4 in sequence, so that the time consumption for cleaning the reagent needle 110 and the consumption of cleaning liquid can be reduced on the premise of ensuring the performance of each reagent.
For example, referring to fig. 8, the cleaning assembly 600 includes an outer wall cleaning syringe 601, a first three-way valve 602, a cleaning tank 603 and a negative pressure generating mechanism 604, wherein the first three-way valve 602 is connected with the outer wall cleaning syringe 601, the cleaning tank 603 and the liquid storage container, the outer wall cleaning syringe 601 can suck cleaning liquid from the liquid storage container through the first three-way valve 602, and the negative pressure generating mechanism 604 is connected with the bottom of the cleaning tank 603.
Referring to fig. 8 in conjunction with fig. 4, the control unit 500 controls the driving unit 150 to move the reagent needle 110 to the cleaning unit 600, and controls the cleaning unit 600 to clean and dry the outer wall of the reagent needle 110, for: the control driving assembly 150 moves the reagent needle 110 to the inside of the washing reservoir 603, and controls the outer wall washing syringe 601 to discharge the washing liquid to the washing reservoir 603 through the first three-way valve 602 so that the washing liquid washes the outer wall of the reagent needle 110; the negative pressure generating mechanism 604 is controlled to discharge the liquid and air inside the washing tub 603 to air-dry the outer wall of the reagent needle 110.
Optionally, the negative pressure generating mechanism 604 includes a diaphragm pump 6041, a vacuum tank 6042 and an electromagnetic valve 6043, when the electromagnetic valve 6043 is opened, the negative pressure in the vacuum tank 6042 sucks the liquid and the gas in the cleaning tank 603, and the gas flow in the cleaning tank 603 can air-dry the reagent needle 110; the diaphragm pump 6041 is used to discharge liquid and gas in the vacuum tank 6042 to form negative pressure in the vacuum tank 6042.
In some embodiments, the control assembly 500 is further used to control the cleaning assembly 600 to clean the inner and outer walls of the reagent needle 110 after the reagent needle 110 discharges the sucked plurality of reagents to the same first reaction vessel E. Illustratively, after the reagent needle 110 discharges the sucked plurality of reagents to the same first reaction vessel E, the driving assembly 150 is controlled to move the reagent needle 110 to the washing assembly 600, and the washing assembly 600 is controlled to wash the inner and outer walls of the reagent needle 110; for example, the reagent needle 110 can be conveniently cleaned for subsequent reagent dispensing; alternatively, the reagent needle 110 is a reusable reagent needle 110.
For example, when the first reagent A1, the second reagent A2, the third reagent A3, and the fourth reagent A4 are previously sucked, and the sucked plural kinds of reagents are discharged to the same first reaction container E, "four suction of one row" may be required only to perform one outer wall cleaning of the reagent needle 110 after sucking the second reagent A2, and one inner wall cleaning and one outer wall cleaning of the reagent needle 110 after discharging the reagent, the time consumption of cleaning of the reagent needle 110 and the consumption of cleaning liquid may be reduced as compared to performing cleaning of the inner wall and the outer wall of the reagent needle 110 each time one reagent is discharged and before sucking another reagent.
In some embodiments, the first reagent sucked by the reagent needle 110 is the first target reagent, and the discharge amount of the first target reagent discharged from the reagent needle 110 to the first reaction container E may be smaller than the suction amount of the first target reagent. That is, the amount of the first target reagent to be suctioned may be larger than the amount of the first target reagent required to prepare the first mixed solution, for example, when the amount of the first reagent A1 required to prepare the first mixed solution is 550 microliters, 600 microliters of the first reagent A1 may be suctioned at the time of suctioning the plurality of reagents.
Illustratively, controlling the fluid path support assembly 130 to cause the reagent needle 110 to discharge the aspirated plurality of reagents to the same first reaction vessel E may include: controlling the liquid path support assembly 130 to cause the reagent needle 110 to discharge all of the second target reagent and a part of the first target reagent sucked up to the same first reaction vessel E; control the driving unit 150 to drive the reagent needle 110 to move to the washing unit 600, and control the liquid path supporting unit 130 to discharge the remaining first target reagent to the washing unit 600; after discharging the first target reagent, the cleaning assembly 600 is controlled to clean the reagent needle 110.
Illustratively, the control assembly 500 is further configured to control the fluid path support assembly 130 to reciprocate the remaining first target reagent within the reagent needle 110 during the process of controlling the fluid path support assembly 130 to discharge the remaining first target reagent to the cleaning assembly 160; after the number of the reciprocating motions reaches a preset number or the time of the reciprocating motions reaches a preset time, the liquid path supporting assembly 130 is controlled to make the reagent needle 110 discharge the remaining first target reagent. Cleaning of the inner wall of the reagent needle 110 by the first target reagent may be achieved by controlling the liquid path support assembly 130 to reciprocate the remaining first target reagent within the reagent needle 110.
Illustratively, the first target reagent such as the first reagent A1 sucked by the reagent needle 110 may be partially discharged into the first reaction container E, and the remaining first reagent A1 may also be discharged into the cleaning assembly 160, so that the cleaning assembly 160 may clean the reagent needle 110 through the first reagent A1, thereby improving the cleaning effect on the reagent needle 110.
In some embodiments, the first target reagent is a lysate, the second target reagent comprises magnetic beads, an internal standard solution, and proteinase K, and after the lysate is aspirated, the magnetic beads, internal standard solution, and proteinase K are aspirated sequentially. After the reagent needle 110 discharges all the second target reagent and part of the first target reagent sucked into the same first reaction vessel E, some proteinase K may remain on the outer wall of the reagent needle 110, and by discharging part of the lysate to the cleaning assembly 160, the proteinase K on the reagent needle 110 may be cleaned by the lysate, so as to improve the cleaning effect on the reagent needle 110.
For example, the driving assembly 150 is controlled to move the reagent needle 110 into the cleaning tank 603, and the liquid path supporting assembly 130 is controlled to discharge the remaining first target reagent, such as the lysate, into the cleaning tank 603; the outer wall washing syringe 601 may also be controlled to discharge the washing liquid to the washing reservoir 603 through the first three-way valve 602 so as to wash the outer wall of the reagent needle 110 by the first target reagent discharged to the washing reservoir 603 and the washing liquid; the inner walls of the reagent line 132 and the reagent needle 110 may also be cleaned by the first target reagent and the cleaning liquid discharged to the cleaning bath 603. After the washing is completed, the negative pressure generating mechanism 604 may be controlled to discharge the liquid and air inside the washing tub 603 to air-dry the outer wall of the reagent needle 110.
In some embodiments, the control assembly 500 controls the cleaning assembly 600 to clean the inner wall of the reagent needle 110 for: the control fluid path support assembly 130 discharges the cleaning fluid to the inner wall of the reagent needle 110; controlling the liquid path support assembly 130 to suck air from the reagent needle 110 so that the sucked air is mixed with the cleaning liquid; the control fluid path support assembly 130 causes the reagent needle 110 to discharge the cleaning fluid of the mixed air. The cleaning solution is mixed with air to obtain a gas-liquid mixed cleaning solution, so that the cleaning effect on the reagent pipeline 132 and the reagent needle 110 is better, the cleaning efficiency can be improved, and the consumption of the cleaning solution can be reduced.
For example, referring to fig. 8, the fluid path support assembly 130 includes a reagent syringe 131, and the cleaning assembly 600 includes an inner wall cleaning syringe 605, a second three-way valve 606. The second three-way valve 606 is connected to the inner wall cleaning syringe 605, the reagent syringe 131, and the liquid storage container, and the inner wall cleaning syringe 605 can suck the cleaning liquid from the liquid storage container through the second three-way valve 606 and discharge the sucked cleaning liquid to the reagent syringe 131, and the reagent syringe 131 can discharge the cleaning liquid to the inner wall of the reagent needle 110. Controlling the reagent injector 131 to suck air from the reagent needle 110 so that the sucked air is mixed with the cleaning liquid; the reagent injector 131 is controlled to discharge the cleaning liquid of the mixed air from the reagent needle 110.
For example, when the control component 500 controls the cleaning component 600 to clean the inner wall of the reagent needle 110, the control component is configured to: controlling the inner wall cleaning syringe 605 to suck part of the air through the reagent needle 110 so that the sucked air is mixed with the cleaning liquid, and mixing the cleaning liquid with the air to obtain a gas-liquid mixed cleaning liquid; the inner wall cleaning syringe 605 is controlled to discharge the gas-liquid mixed cleaning liquid through the second three-way valve 606, the reagent syringe 131 and the reagent needle 110. When the inner wall cleaning syringe 605 discharges the gas-liquid mixed cleaning liquid to the reagent line 132 and the reagent needle 110 through the second three-way valve 606 and the reagent syringe 131, the gas-liquid mixed cleaning liquid cleans the inner walls of the reagent line 132 and the reagent needle 110, and the cleaning effect is better.
Optionally, before controlling the inner wall cleaning syringe 605 to suck part of the air through the reagent needle 110 to mix the sucked air with the cleaning liquid, controlling the reagent syringe 131 to discharge the reagent before the reagent needle 110 is discharged from the first air column X and the first air column X, that is, the reagent remaining in the reagent line 132 and the reagent needle 110 and the first air column X can be discharged first, so as to reduce the time consumption and the consumption of the cleaning liquid when cleaning the inner wall of the reagent needle 110 later.
Optionally, as shown in fig. 8, the reagent tube 132 is provided with a needle blocking sensor 133, where the needle blocking sensor 133 is used to detect whether the reagent tube 132 and the reagent needle 110 are blocked by a foreign object, for example, when the reagent tube 132 and the reagent needle 110 are detected to be blocked by a foreign object, the control assembly 500 may also control the cleaning assembly 600 to clean the interior of the reagent needle 110 so as to remove the foreign object.
In some embodiments, the operation of the reagent dispensing device 100 includes the steps of:
After the reagent injector 131, the inner wall cleaning injector 605 and the outer wall cleaning injector 601 are reset, the reagent injector 131 performs the action of sucking a1ul of liquid to enable the reagent needle 110 to suck the first air column X; for example, the reagent injector 131 is empty when reset, the inner wall cleaning injector 605 and the outer wall cleaning injector 601 draw cleaning fluid from the reservoir when reset, and in some embodiments, the system fluid C1 in fig. 5 may be the cleaning fluid;
The reagent needle 110 is driven by the driving component 150 to the reagent container A of the first reagent A1 to suck the first reagent A1, the reagent injector 131 executes the action of sucking a2ul of the first reagent A1, and after the sucking is finished, the driving component 150 drives the reagent needle 110 to lift off the liquid level at a low speed so as to reduce the hanging liquid of the needle point;
The reagent needle 110 is driven by the driving component 150 to the reagent container A of the second reagent A2, the needle opening descends to the lower side of the liquid surface, the reagent injector 131 executes the action of sucking a3ul of the liquid, the second reagent A2 is sucked, and the reagent needle 110 is lifted off the liquid surface slowly;
The reagent needle 110 is driven to the cleaning assembly 600 by the driving assembly 150, the needle opening is lowered into the cleaning pool 603 of the cleaning assembly 600, the outer wall is cleaned with the injector 601 to drain liquid, and meanwhile, the negative pressure generating mechanism 604 is opened to pump away the waste liquid and air in the cleaning pool 603, and the outer wall of the reagent needle 110 is air-dried;
The reagent needle 110 is driven by the driving component 150 to the reagent container A of the third reagent A3, the needle opening descends to the lower side of the liquid surface, the reagent injector 131 executes the action of sucking a4ul liquid, the third reagent A3 is sucked, and the reagent needle 110 is lifted off the liquid surface slowly;
The reagent needle 110 is driven by the driving component 150 to the reagent container A of the fourth reagent A4, the needle opening descends to the lower side of the liquid surface, the reagent injector 131 executes the action of sucking a5ul liquid, the fourth reagent A4 is sucked, and the reagent needle 110 is lifted off the liquid surface slowly;
The reagent needle 110 is driven by the driving assembly 150 to discharge 4 reagents into the first reaction vessel E, the volume of the discharged liquid being (a2+a3+a4+a5) ul; optionally, when the liquid discharge starts, the needle tip of the reagent needle 110 is at a position lower than the bottom of the first reaction container E, for example, a bottom reducing area of the first reaction container E, after the liquid surface passes through the needle tip, the reagent needle 110 is driven by the driving assembly 150 to move upward slowly along with the liquid surface, until the liquid discharge is completed, the reagent needle 110 is lifted away from the liquid surface slowly, and after the reagent needle is lifted away from the liquid surface, an air column can be sucked for isolation.
The reagent needle 110 is driven to the cleaning component 600 by the driving component 150, the reagent injector 131 executes the zeroing action, the residual reagent and air in the reagent needle 110 are discharged, then V1ul (e.g. 300 ul) of air is sequentially sucked by the inner wall cleaning injector 605, V1ul of air is discharged, so that the cleaning liquid in the reagent needle 110 reaches the gas-liquid mixing state to improve the cleaning capability, and finally V2ul (e.g. 2300 ul) of cleaning liquid is discharged by the inner wall cleaning injector 605 to finish the inner wall cleaning; the inner wall cleaning efficiency of the reagent needle 110 is improved and the consumption of cleaning liquid is reduced by repeatedly flushing the inner wall of the reagent needle 110 and the inner wall of the sample adding pipe. Optionally, there may be a delay between each of the actions of sucking V1ul (e.g. 300 ul) of air, exhausting V1ul of air, sucking V1ul of air, exhausting V1ul of air in order to perform sufficient gas-liquid mixing and cleaning.
In some embodiments, the first reagent A1 has a large liquid absorption amount, and after the liquid absorption is completed, more first reagent A1 is contained in the reagent pipeline 132, and the reagent needle 110 is subjected to vibration cleaning in a gas-liquid mixing manner, so that the cleaning efficiency can be effectively improved, and the consumption of the cleaning liquid can be reduced by flushing the inner walls of the reagent needle 110 and the reagent pipeline 132 with the cleaning liquid mixed with the gas-liquid.
It should be noted that, the repeated sucking and discharging operation during the cleaning of the inner wall of the reagent needle 110 may be adjusted from two times to more than two times, or may be adjusted to one time, depending on the capability of the cleaning liquid to clean the reagent; for example, the cleaning effect of the reagent needle 110 may be determined based on the test result, and the number of repeated suction and discharge operations may be adjusted based on the cleaning effect of the reagent needle 110.
Optionally, after the inner wall cleaning is completed, the outer wall cleaning action of the reagent needle 110 is performed.
The sample analyzer provided by the embodiment of the application comprises a reagent storage device 10, a reagent dispensing device 100, a sample dispensing device 200, a nucleic acid extraction device 300, an amplification device 410, a detection device 420 and a control component 500, wherein the reagent dispensing device 100 comprises a reagent needle 110 and a liquid path support component 130, and the reagent needle 110 is used for sucking and discharging a reagent; the liquid path support assembly 130 is connected to the reagent needle 110 and serves to provide power for sucking and discharging the reagent to the reagent needle 110; the control component 500 is used for controlling the liquid path support component 130 to enable the same reagent needle 110 to absorb the first air column X, and controlling the liquid path support component 130 to enable the reagent needle 110 to absorb a plurality of reagents in the reagent container A after the first air column X is absorbed; the control fluid path support assembly 130 causes the reagent needle 110 to discharge the sucked plurality of reagents to the same first reaction container E. Multiple reagents can be dispensed in one reagent dispensing flow; compared with the method that each time one reagent is sucked, the sucked reagent is distributed to the first reaction container E, so that the reagent distribution efficiency can be improved; the reagent discharged later may carry out the part of the reagent discharged earlier remaining in the reagent needle 110 into the first reaction vessel E, and may improve the utilization ratio of the reagent.
Referring to fig. 3 in combination with the foregoing embodiments, fig. 3 is a schematic structural diagram of a reagent dispensing device 100 according to an embodiment of the present application. Reagent dispensing device 100 may be used in a sample analyzer. In some embodiments, the sample analyzer includes, but is not limited to, at least one of: molecular diagnostic apparatus, biochemical analyzer, immunoassay analyzer. The molecular diagnostic instrument is, for example, a nucleic acid extractor or a nucleic acid detector. Reagent dispensing device 100 may be a reagent dispensing device in any of the sample analyzers. For convenience of explanation, a sample analyzer will be mainly described as a molecular diagnostic apparatus. Illustratively, the sample analyzer is a nucleic acid detection device.
As shown in fig. 3, a reagent dispensing device 100 according to an embodiment of the present application includes: a reagent needle 110, a fluid path support assembly 130, and a control assembly 140. Note that, the control unit 140 in the reagent dispensing device 100 may be the control unit 500 of the sample analyzer, which is not limited to this.
A reagent needle 110, the reagent needle 110 for sucking and discharging a reagent;
A liquid path support assembly 130, the liquid path support assembly 130 being connected to the reagent needle 110 and for providing power for sucking and discharging the reagent to the reagent needle 110;
a control assembly 140, the control assembly 140 being configured to:
Controlling the fluid path support assembly 130 to cause the same reagent needle 110 to draw a first column of air X;
And controlling the liquid path support assembly 130 to make the reagent needle 110 sequentially suck a plurality of reagents in the reagent container a after sucking the first air column X; and
The control fluid path support assembly 130 causes the reagent needle 110 to discharge the plurality of reagents sucked up to the same reaction vessel.
In some embodiments, the reagent dispensing device 100 comprises a drive assembly 150, the drive assembly 150 being configured to drive the reagent needle 110 between the reagent storage device 10 and the position of the reaction vessel, the control assembly 140 further being configured to: the liquid path support assembly 130 is controlled to suck the first air column X from the same reagent needle 110 before the driving assembly 150 drives the reagent needle 110 to move toward the reagent container a, or during the driving assembly 150 drives the reagent needle 110 to move toward the reagent container a, or after the driving assembly 150 drives the reagent needle 110 to move toward the reagent container a.
In some embodiments, the controlling the liquid path support assembly 130 to sequentially suck the plurality of reagents in the reagent vessel a by the reagent needle 110 after sucking the first air column X includes:
controlling the fluid path support assembly 130 to cause the reagent needle 110 to aspirate the first target reagent;
After the reagent needle 110 suctions the first target reagent, controlling the liquid path support assembly 130 to cause the reagent needle 110 to suction the second air columns Y1 to Y4;
The control fluid path support assembly 130 causes the reagent needle 110 to aspirate at least one second target reagent after aspirating the second air columns Y1-Y4.
In some embodiments, the sample analyzer further comprises a cleaning assembly 600, the cleaning assembly 600 is used for cleaning the reagent needle 110, and the controlling the liquid path supporting assembly 130 to make the reagent needle 110 discharge the sucked multiple reagents into the same reaction container comprises:
Controlling the liquid path support assembly 130 to cause the reagent needle 110 to discharge all of the second target reagent and part of the first target reagent sucked up to the same reaction container;
control the driving unit 150 to drive the reagent needle 110 to move to the washing unit 600, and control the liquid path supporting unit 130 to discharge the remaining first target reagent to the washing unit 600;
After discharging the first target reagent, the cleaning assembly 600 is controlled to clean the reagent needle 110.
In some embodiments, after the reagent needle 110 aspirates the second column of air Y1-Y4 and before aspirating the second target reagent, the drive assembly 150 is controlled to move the reagent needle 110 to the washing assembly 600, and the washing assembly 600 is controlled to wash the outer wall of the reagent needle 110.
In some embodiments, the second target reagent includes at least two reagents, and the second target reagent includes a first type reagent and a second type reagent, the first type reagent has higher adsorptivity to the reagent needle 110 than the second type reagent, the reagent needle 110 sucks the first type reagent before sucking the second type reagent when sucking the second target reagent, and the control component 140 is further configured to control the cleaning component 600 to clean the reagent needle 110 after the reagent needle 110 sucks the first type reagent, and control the liquid path support component 130 to make the reagent needle 110 suck the second type reagent in the second target reagent after the reagent needle 110 cleans.
In some embodiments, the control assembly 140 is further configured to control the liquid path support assembly 130 to reciprocate the remaining first target reagent within the reagent needle 110 during the process of discharging the remaining first target reagent to the cleaning assembly 600 by the control liquid path support assembly 130; after the number of the reciprocating motions reaches a preset number or the time of the reciprocating motions reaches a preset time, the liquid path supporting assembly 130 is controlled to make the reagent needle 110 discharge the remaining first target reagent.
In some embodiments, the first target reagent is a lysate, the second target reagent comprises magnetic beads, an internal standard solution, and proteinase K, and after the lysate is aspirated, the magnetic beads, internal standard solution, and proteinase K are aspirated sequentially.
In some embodiments, the second target reagent includes at least two types, and after each aspiration of one of the second target reagents, the liquid support assembly 130 is controlled to aspirate the reagent needle 110 with a second column of air Y1-Y4.
In some embodiments, the amount of the first target reagent discharged from the reagent needle 110 to the reaction vessel is greater than the amount of the at least one second target reagent aspirated after the first target reagent.
In some embodiments, the amount of the first target reagent discharged from the reagent needle 110 to the reaction vessel is greater than or equal to the sum of the amounts of the second target reagent sucked thereafter.
In some embodiments, the fluid path support assembly 130 includes a reagent syringe 131 and a reagent line 132, the reagent needle 110 being connected to the reagent syringe 131 through the reagent line 132; the sum of the volume of the reagent needle 110 and the volume of the reagent line 132 is greater than the sum of the volumes of the reagent and the column of air drawn by the reagent needle 110, and the volume of the reagent needle 110 is less than the sum of the volumes of the first target reagent, the second target reagent, and the column of first air X drawn by the reagent needle 110.
In some embodiments, the sample analyzer further comprises a cleaning assembly 600, wherein the cleaning assembly 600 is configured to clean the reagent needle 110, and the control assembly 140 is further configured to control the cleaning assembly 600 to clean the inner wall and the outer wall of the reagent needle 110 after the reagent needle 110 discharges the sucked plurality of reagents into the same reaction vessel.
In some embodiments, the control assembly 140 controls the cleaning assembly 600 to clean the inner wall of the reagent needle 110 for:
The control fluid path support assembly 130 discharges the cleaning fluid to the inner wall of the reagent needle 110;
Controlling the liquid path support assembly 130 to suck air from the reagent needle 110 so that the sucked air is mixed with the cleaning liquid;
The control fluid path support assembly 130 causes the reagent needle 110 to discharge the cleaning fluid of the mixed air.
The reagent dispensing device 100 provided by the embodiment of the application comprises a reagent needle 110, a liquid path supporting component 130 and a control component 140, wherein the reagent needle 110 is used for sucking and discharging a reagent; the liquid path support assembly 130 is connected to the reagent needle 110 and serves to provide power for sucking and discharging the reagent to the reagent needle 110; the control assembly 140 is configured to: the control fluid path support assembly 130 enables the same reagent needle 110 to absorb the first air column X, and after absorbing the first air column X, the control fluid path support assembly 130 enables the reagent needle 110 to absorb a plurality of reagents in the reagent container A in sequence; and controlling the liquid path support assembly 130 to cause the reagent needle 110 to discharge the plurality of reagents sucked up to the same reaction container. Multiple reagents can be dispensed in one reagent dispensing flow; compared with the method that each time one reagent is sucked, the sucked reagent is distributed to the reaction container, so that the reagent distribution efficiency can be improved; the reagent discharged later can bring out the part of the reagent discharged earlier remaining in the reagent needle 110 into the reaction vessel, and the utilization ratio of the reagent can be improved.
The specific principle and implementation of the reagent dispensing device 100 according to the embodiment of the present application are similar to those of the sample analyzer according to the previous embodiment, and will not be described here again.
Referring to fig. 9 in combination with the foregoing embodiments, fig. 9 is a flow chart of a reagent dispensing method according to an embodiment of the present application.
As shown in fig. 9, the reagent dispensing method includes the following steps S110 to S130.
Step S110, sucking a first air column through a reagent needle;
Step S120, after the first air column is sucked, sequentially sucking a plurality of reagents through the same reagent needle;
Step S130, discharging the plurality of sucked reagents to the same reaction container through the reagent needle.
In some embodiments, the sequentially drawing a plurality of reagents through the same reagent needle after drawing the first column of air comprises: and after the first air column is sucked, sequentially sucking a first target reagent, a second air column and at least one second target reagent through the same reagent needle.
In some embodiments, the discharging the plurality of reagents aspirated through the reagent needle into the same reaction vessel comprises: discharging all of the second target reagent sucked up and part of the first target reagent to the same reaction vessel through the reagent needle; moving the reagent needle to a wash assembly and discharging the remaining first target reagent to the wash assembly; after discharging the first target reagent, the cleaning assembly is controlled to clean the reagent needle.
In some embodiments, the first target reagent is a lysate, the second target reagent comprises magnetic beads, an internal standard solution, and proteinase K, and after the lysate is aspirated, the magnetic beads, internal standard solution, and proteinase K are aspirated sequentially.
The specific principle and implementation manner of the reagent dispensing method provided by the embodiment of the present application are similar to those of the reagent dispensing device and the sample analyzer in the foregoing embodiment, and are not repeated here.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.
It should also be understood that the term "and/or" as used in the present application and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes such combinations.
While the application has been described with reference to certain preferred embodiments, it will be understood by those skilled in the art that various changes and substitutions of equivalents may be made and equivalents will be apparent to those skilled in the art without departing from the scope of the application. Therefore, the protection scope of the application is subject to the protection scope of the claims.
Claims (18)
1. A sample analyzer, comprising:
a reagent storage device for housing a reagent container;
a reagent dispensing device for dispensing a plurality of extraction reagents in the reagent container to a first reaction container;
a sample dispensing device for dispensing a sample to the first reaction vessel, the sample and the extraction reagent forming a first mixed solution;
a nucleic acid extraction device for extracting nucleic acid from the first mixed solution in the first reaction vessel; the sample dispensing device is further used for transferring the nucleic acid in the first reaction container to a second reaction container, and the nucleic acid and the amplification reagent in the second reaction container form a second mixed solution;
An amplification device for amplifying nucleic acids in the second mixed solution;
A detection device for detecting the amplified nucleic acid;
the reagent dispensing device includes:
a reagent needle for sucking up a reagent and discharging the reagent;
A liquid path support assembly connected to the reagent needle and for providing motive power for sucking and discharging a reagent to the reagent needle through a liquid;
the sample analyzer further comprises a control assembly for:
Controlling the liquid path supporting component to enable the same reagent needle to absorb a first air column;
controlling the liquid path support assembly after the first air column is sucked so that the reagent needle sequentially sucks a plurality of reagents in the reagent container;
Controlling the liquid path support assembly to enable the reagent needle to discharge the sucked multiple reagents to the same first reaction container.
2. The sample analyzer of claim 1, wherein the reagent dispensing device includes a drive assembly for driving the reagent needle between the reagent storage device and the location of the first reaction vessel, the control assembly further for:
The liquid path support component is controlled to enable the same reagent needle to suck a first air column before the driving component drives the reagent needle to move towards the reagent container, or during the process of driving the reagent needle to move towards the reagent container, or after the driving component drives the reagent needle to move towards the reagent container.
3. The sample analyzer of claim 1, wherein said controlling said fluid path support assembly after said first column of air to cause said reagent needle to sequentially aspirate a plurality of reagents in a reagent container comprises:
Controlling the liquid path support assembly to enable the reagent needle to suck a first target reagent;
After the reagent needle sucks the first target reagent, controlling the liquid path support component to suck the second air column by the reagent needle;
And controlling the liquid path supporting component to enable the reagent needle to suck at least one second target reagent after sucking the second air column.
4. The sample analyzer of claim 3, further comprising a cleaning assembly for cleaning the reagent needle, the controlling the fluid path support assembly to cause the reagent needle to discharge the plurality of reagents aspirated into the same first reaction vessel comprising:
controlling the liquid path support assembly to enable the reagent needle to discharge all the sucked second target reagent and part of the first target reagent to the same first reaction container;
controlling a driving assembly to drive the reagent needle to move to the cleaning assembly, and controlling the liquid path supporting assembly to discharge the residual first target reagent to the cleaning assembly;
After discharging the first target reagent, the cleaning assembly is controlled to clean the reagent needle.
5. The sample analyzer of claim 4, wherein the drive assembly is controlled to move the reagent needle to the purge assembly after the reagent needle aspirates the second column of air and before aspirating the second target reagent, and wherein the purge assembly is controlled to purge an outer wall of the reagent needle.
6. The sample analyzer of claim 3 wherein said second target reagent comprises at least two and said second target reagent comprises a first type reagent and a second type reagent, said first type reagent having a greater adsorptivity to said reagent needle than said second type reagent, said reagent needle aspirating said first type reagent prior to aspirating said second type reagent when aspirating said second target reagent, said control assembly further configured to control a wash assembly to wash said reagent needle after said reagent needle aspirating said first type reagent, and to control said fluid path support assembly to cause said reagent needle to aspirate said second type reagent of said second target reagent after said reagent needle has been washed.
7. The sample analyzer of claim 4, wherein said control assembly is further configured to control said fluid path support assembly to reciprocate the remaining first target reagent within said reagent needle during said controlling said fluid path support assembly to discharge the remaining first target reagent to said washing assembly; and controlling the liquid path support assembly to enable the reagent needle to discharge the residual first target reagent after the number of the reciprocating motions reaches a preset number or the time of the reciprocating motions reaches a preset time.
8. The sample analyzer of any of claims 3-6, wherein the first target reagent is a lysate and the second target reagent comprises magnetic beads, an internal standard solution, and proteinase K, and wherein after the lysate is aspirated, the magnetic beads, the internal standard solution, and proteinase K are aspirated sequentially.
9. The sample analyzer of any of claims 3-6, wherein the second target reagent comprises at least two, and wherein after each aspiration of one of the second target reagents, the liquid path support assembly is controlled to aspirate a second column of air with the reagent needle.
10. The sample analyzer of any of claims 3-6, wherein the reagent needle discharges a greater amount of the first target reagent to the first reaction vessel than at least one second target reagent aspirated after the first target reagent.
11. The sample analyzer of any of claims 3-6, wherein the amount of the first target reagent discharged from the reagent needle into the first reaction vessel is greater than or equal to the sum of the amounts of the second target reagent aspirated thereafter.
12. The sample analyzer of claim 1 or 2, wherein the fluid path support assembly comprises a reagent syringe and a reagent line, the reagent needle being connected to the reagent syringe by the reagent line; the sum of the volume of the reagent needle and the volume of the reagent pipeline is larger than the sum of the volumes of the reagent and the air column sucked by the reagent needle, and the volume of the reagent needle is smaller than the sum of the volumes of the first target reagent, the second target reagent and the first air column sucked by the reagent needle.
13. A sample analyzer according to any of claims 1-3, further comprising a cleaning assembly for cleaning the reagent needle, the control assembly further being adapted to control the cleaning assembly to clean the inner and outer walls of the reagent needle after the reagent needle discharges the plurality of reagents aspirated into the same first reaction vessel.
14. The sample analyzer of claim 13, wherein the control assembly controls the cleaning assembly to clean the interior wall of the reagent needle to:
Controlling the liquid path supporting component to discharge cleaning liquid to the inner wall of the reagent needle;
controlling the liquid path support assembly to suck air from the reagent needle so as to mix the sucked air with the cleaning liquid;
and controlling the liquid path supporting component to enable the reagent needle to discharge the cleaning liquid of the mixed air.
15. A reagent dispensing device, comprising:
a reagent needle for sucking up a reagent and discharging the reagent;
A fluid path support assembly connected to the reagent needle and adapted to provide motive power for sucking and discharging a reagent to the reagent needle;
a control assembly for:
Controlling the liquid path supporting component to enable the same reagent needle to absorb a first air column;
Controlling the liquid path support assembly after the first air column is sucked so that the reagent needle sequentially sucks a plurality of reagents in the reagent container; and
And controlling the liquid path supporting component to enable the reagent needle to discharge the sucked multiple reagents into the same reaction container.
16. A method of dispensing a reagent, comprising:
Sucking a first air column through a reagent needle;
sequentially sucking a plurality of reagents through the same reagent needle after sucking the first air column;
The plurality of reagents sucked up are discharged to the same reaction vessel through the reagent needle.
17. The reagent dispensing method according to claim 16, wherein the sucking up a plurality of reagents through the same reagent needle after sucking up the first air column, comprises: sequentially sucking a first target reagent, a second air column and at least one second target reagent through the same reagent needle after sucking the first air column;
Said discharging said plurality of reagents sucked up through said reagent needle to the same reaction vessel, comprising:
Discharging all of the second target reagent sucked up and part of the first target reagent to the same reaction vessel through the reagent needle;
moving the reagent needle to a wash assembly and discharging the remaining first target reagent to the wash assembly;
After discharging the first target reagent, the cleaning assembly is controlled to clean the reagent needle.
18. The reagent dispensing method according to claim 17, wherein the first target reagent is a lysate, the second target reagent comprises magnetic beads, an internal standard solution and proteinase K, and the magnetic beads, the internal standard solution and proteinase K are sequentially sucked after sucking the lysate.
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CN202211685976 | 2022-12-27 | ||
CN2022116859768 | 2022-12-27 |
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CN202311835153.3A Pending CN118259039A (en) | 2022-12-27 | 2023-12-27 | Reagent dispensing device, reagent dispensing method, and sample analyzer |
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