CN117899956A - Automatic pipetting method, automatic pipetting device and immunoassay system - Google Patents
Automatic pipetting method, automatic pipetting device and immunoassay system Download PDFInfo
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- CN117899956A CN117899956A CN202311857366.6A CN202311857366A CN117899956A CN 117899956 A CN117899956 A CN 117899956A CN 202311857366 A CN202311857366 A CN 202311857366A CN 117899956 A CN117899956 A CN 117899956A
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- 238000003018 immunoassay Methods 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000005070 sampling Methods 0.000 claims abstract description 195
- 238000006243 chemical reaction Methods 0.000 claims abstract description 154
- 239000007788 liquid Substances 0.000 claims abstract description 106
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 91
- 238000004140 cleaning Methods 0.000 claims abstract description 84
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 71
- 230000005291 magnetic effect Effects 0.000 claims abstract description 71
- 239000002699 waste material Substances 0.000 claims abstract description 59
- 238000002347 injection Methods 0.000 claims abstract description 36
- 239000007924 injection Substances 0.000 claims abstract description 36
- 238000007599 discharging Methods 0.000 claims abstract description 13
- 238000011534 incubation Methods 0.000 claims description 28
- 238000005406 washing Methods 0.000 claims description 23
- 239000012530 fluid Substances 0.000 claims description 10
- 238000004891 communication Methods 0.000 claims description 8
- 230000007246 mechanism Effects 0.000 abstract description 16
- 238000000926 separation method Methods 0.000 abstract description 16
- 239000000872 buffer Substances 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 28
- 239000011324 bead Substances 0.000 description 10
- 239000000758 substrate Substances 0.000 description 9
- 238000010586 diagram Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000009471 action Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5302—Apparatus specially adapted for immunological test procedures
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
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Abstract
The application relates to an automatic pipetting method, an automatic pipetting device and an immunoassay system, wherein the automatic pipetting method comprises the steps of grabbing a reaction cup through a gripper device and moving the reaction cup to a sample adding position of a magnetic collecting device; injecting a first preset reaction liquid into the reaction cup through sampling needle equipment; controlling the sampling needle equipment to move to the cleaning pool and cleaning the sampling needle of the sampling needle equipment; injecting a second preset reaction liquid into the reaction cup through the first liquid injection equipment; and sucking out the waste liquid in the reaction cup through the sampling needle after the cleaning operation. The automatic pipetting method provided by the application enables sample adding and cleaning separation operations to be completed through the sampling needle equipment and the first liquid injection equipment, and is simple in operation; and the independent sample sucking and discharging mechanism and the reagent sucking and discharging mechanism are not required to be additionally arranged, the sample, the reagent or the cleaning buffer liquid is not required to be additionally injected through the liquid injection mechanism, and the waste liquid sucking and discharging mechanism is not required to suck and discharge the waste liquid in the reaction cup, so that the structure is simple.
Description
Technical Field
The application relates to the technical field of medical detection equipment, in particular to an automatic pipetting method, an automatic pipetting device and an immunoassay system.
Background
The immunoassay technology has been applied more and more in recent years due to the advantages of high sensitivity, good specificity, wide linear range, high throughput, strong platform expansibility, abundant menu of measurable items, etc. In the detection process of immunoassay, the sample carried in the reaction cup needs to be taken, and after the sample finishes the corresponding reaction, the sample is cleaned and separated. However, in the related art, the operations of sample loading, cleaning and separating are complicated, so that the whole immunoassay detection process is time-consuming and labor-consuming, and the immunoassay system is complex in structure and high in cost.
Disclosure of Invention
Based on the above, it is necessary to provide an automatic pipetting method for the problems that in the immunoassay detection process, sample loading and cleaning and separating operations are complicated, the structure of the immunoassay system is complex, and the cost is high.
An automated pipetting method for immunoassays, comprising:
grabbing and moving the reaction cup to a sample adding position of the magnetic collecting device through a grabbing device;
injecting a first preset reaction liquid into the reaction cup through sampling needle equipment;
Controlling the sampling needle equipment to move to a cleaning pool, and cleaning the sampling needle of the sampling needle equipment;
Injecting a second preset reaction liquid into the reaction cup through a first liquid injection device;
And sucking out the waste liquid in the reaction cup through the sampling needle after the cleaning operation.
In one embodiment, the step of injecting the first preset reaction solution into the reaction cup through the sampling needle device specifically includes:
controlling the magnetic collection device to move along a first direction so that the sample adding position is positioned at a first preset position;
Controlling the sampling needle device to move to the reagent sample loading device, and sucking the first preset reaction liquid through the sampling needle;
And controlling a sampling needle for sucking the first preset reaction liquid to move to the magnetic collection device, and injecting the first preset reaction liquid into the reaction cup through the sampling needle.
In one embodiment, the step of controlling the sampling needle device to move to the cleaning pool and performing cleaning operation on the sampling needle of the sampling needle device specifically includes:
controlling the sampling needle to move so as to enable the sampling needle to move into the cleaning pool;
and cleaning the inner wall and the outer wall of the sampling needle through the cleaning pool.
In one embodiment, the step of injecting the second preset reaction liquid into the reaction cup through the first liquid injection device further includes:
Grabbing and moving the reaction cup into an incubation hole of an incubation device through the gripper device;
Performing incubation operation on a first preset reaction liquid in the reaction cup through the incubation equipment;
And grabbing and moving the reaction cup which completes the incubation operation to a collection position of the magnetic collection device through the grabbing device.
In one embodiment, the step of sucking out the waste liquid in the reaction cup through the sampling needle device after the cleaning operation specifically includes:
Controlling the magnetic collection device to move along a first direction so as to enable the reaction cup at the collection position to move to a first preset position;
performing magnetic collection operation on the second preset reaction liquid in the reaction cup through the magnetic collection equipment;
And sucking out the waste liquid in the reaction cup after the magnetic collection operation through the sampling needle after the cleaning operation.
In one embodiment, after the step of sucking out the waste liquid in the reaction cup after the magnetic collection operation by the sampling needle after the washing operation, the method further comprises:
And controlling the sampling needle equipment to move to the cleaning pool, and performing secondary cleaning operation on the sampling needle of the sampling needle equipment.
The present application also provides an automatic pipetting device comprising:
a controller;
The magnetic collection device is electrically connected with the controller and is provided with a sample adding position and a collection position, and the sample adding position and the collection position are used for bearing a reaction cup;
The gripper device is electrically connected with the controller, can be close to or far away from the magnetic collection device and is used for grabbing and moving the reaction cup into or out of the sample adding position or the collection position;
The sampling needle device is electrically connected with the controller, can be close to or far away from the magnetic collecting device, and comprises a sampling needle for sucking a first preset reaction liquid and discharging the first preset reaction liquid into the reaction cup; the sampling needle is also used for sucking out waste liquid in the reaction cup;
The cleaning pool is used for cleaning the sampling needle;
The first liquid injection device is electrically connected with the controller and is used for injecting second preset reaction liquid into the reaction cup located in the collecting position.
In one embodiment, the controller is configured to perform control operations including:
controlling the gripper equipment to grasp and move the reaction cup to the sample adding position;
controlling the sampling needle device to inject the first preset reaction liquid into the reaction cup;
Controlling the sampling needle equipment to move to the cleaning pool and cleaning the sampling needle;
Controlling the first liquid injection equipment to inject a second preset reaction liquid into the reaction cup;
and controlling the sampling needle equipment after the cleaning operation to suck out the waste liquid in the reaction cup.
In one embodiment, the automated pipetting device further comprises a reagent sample loading apparatus comprising a first reagent carrier for carrying a first preset reaction liquid;
The controller controls the sampling needle device to approach or depart from the reagent sample loading device and aspirate the first preset reaction liquid through the sampling needle in the first reagent carrier.
In one embodiment, the sampling needle device further comprises a fluid path assembly;
The liquid path component is connected with the controller, and the liquid path component is connected with the sampling needle, and the liquid path component is used for enabling the sampling needle to suck or discharge the first preset reaction liquid or the waste liquid.
In one embodiment, the fluid circuit assembly includes:
A syringe comprising a body and a plunger; the body is provided with a sliding cavity, the plunger is connected with the controller, and the plunger is at least partially accommodated in the sliding cavity and is in sliding connection with the cavity wall of the sliding cavity; a first interface and a second interface are constructed on the sliding cavity, and the first interface is communicated with the sampling needle;
The first control valve is connected with the controller and is communicated with the second interface;
When the sampling needle sucks the first preset reaction liquid or the waste liquid, the first control valve is closed, and the plunger moves towards one side away from the bottom wall of the sliding cavity so as to reduce the air pressure in the sliding cavity;
When the sampling needle discharges the first preset reaction liquid or the waste liquid, the first control valve is closed, and the plunger moves towards one side close to the bottom wall of the sliding cavity so as to increase the air pressure in the sliding cavity.
In one embodiment, the first liquid injection device comprises a second reagent carrier for carrying the second preset reaction liquid;
The liquid path assembly further comprises a second control valve, the second control valve is connected with the controller, and the second control valve is a three-way valve; the second control valve is connected between the first interface and the sampling needle; the second control valve is also in communication with the second reagent carrier;
when the first liquid injection device injects second preset reaction liquid into the reaction cup in the collecting position, the first control valve is closed, the second control valve is opened, and the plunger moves towards one side close to the bottom wall of the sliding cavity.
The application also provides an immunoassay system comprising the automatic pipetting device according to any one of the embodiments.
When the automatic pipetting method is used for adding, taking, cleaning and separating samples on an immunoassay system, the reaction cup is grabbed by the gripper device and moved to the sample adding position of the magnetic collecting device, and then a first preset reaction liquid is injected into the reaction cup by the sampling needle device, wherein the first preset reaction liquid can be a sample in a sample tube and/or a preset reagent in a kit. After the first preset reaction liquid is injected, the sampling needle of the sampling needle device is subjected to cleaning operation. And injecting a second preset reaction liquid into the reaction cup through the first liquid injection device, wherein the second preset reaction liquid can be a cleaning separation buffer liquid. Finally, the waste liquid in the reaction cup is sucked out through the sampling needle after the cleaning operation, and the waste liquid is the unbound part of the reagent which needs to be removed after the reaction cup is cleaned. According to the automatic pipetting method provided by the application, under the cooperative cooperation of the hand grip device, the magnetic collection device, the sampling needle device, the first liquid injection device and the cleaning pool, the sample adding and cleaning separation operation can be completed through the sampling needle device and the first liquid injection device, so that the sample adding and cleaning separation operation of the sample and/or the preset reagent is simpler; and no separate sample sucking and discharging mechanism and reagent sucking and discharging mechanism are required to be additionally arranged; the sample, the reagent or the cleaning buffer solution are not required to be injected through the liquid injection mechanism, and the waste liquid in the reaction cup is not required to be sucked and discharged through the separate waste liquid sucking mechanism, so that the automatic liquid transferring device of the immunoassay system is simpler in structure, smaller in size and lower in manufacturing cost in the preparation process.
Drawings
Fig. 1 is a schematic flow chart of an automatic pipetting method according to some embodiments of the application.
Fig. 2 is a schematic diagram of an automatic pipetting device according to some embodiments of the application mounted to an immunoassay system.
Fig. 3 is a top view of the immunoassay system shown in fig. 2.
Fig. 4 is a schematic diagram of a magnetic collection device in the immunoassay system shown in fig. 3.
Fig. 5 is a schematic diagram of a sampling needle device in the immunoassay system shown in fig. 3.
Fig. 6 is a schematic diagram of a fluid circuit assembly of a sampling needle device in the immunoassay system shown in fig. 3.
Reference numerals: 100-gripper equipment; 200-magnetic collection device; 210-sample adding position; 220-collection site; 300-sampling needle device; 310-sampling needle; 400-reaction cup loading device; 500-a first liquid injection device; 510-a second reagent carrier; 520-a third reagent carrier; 600-reagent sample loading device; 610-a first reagent carrier; 700-incubation device; 710-incubating the wells; 800-a liquid path assembly; 810-a syringe; 811-a body; 8111-sliding chamber; 8112-first interface; 8113-second interface; 812-plunger; 820-a first control valve; 830-a second control valve; 840-a cleaning waste carrier; 850-substrate priming; 860-substrate carrier; 870-injection mechanism; 900-waste cup channel; 1000-a cleaning pool; 1100-reaction cup.
Detailed Description
In order that the above objects, features and advantages of the application will be readily understood, a more particular description of the application will be rendered by reference to the appended drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. The present application may be embodied in many other forms than described herein and similarly modified by those skilled in the art without departing from the spirit of the application, whereby the application is not limited to the specific embodiments disclosed below.
In the description of the present application, it should be understood that, if any, these terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., are used herein with respect to the orientation or positional relationship shown in the drawings, these terms refer to the orientation or positional relationship for convenience of description and simplicity of description only, and do not indicate or imply that the apparatus or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore should not be construed as limiting the application.
Furthermore, the terms "first," "second," and the like, if any, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the present application, the terms "plurality" and "a plurality" if any, mean at least two, such as two, three, etc., unless specifically defined otherwise.
In the present application, unless explicitly stated and limited otherwise, the terms "mounted," "connected," "secured," and the like are to be construed broadly. For example, the two parts can be fixedly connected, detachably connected or integrated; can be mechanically or electrically connected; either directly or indirectly, through intermediaries, or both, may be in communication with each other or in interaction with each other, unless expressly defined otherwise. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art according to the specific circumstances.
In the present application, unless expressly stated or limited otherwise, the meaning of a first feature being "on" or "off" a second feature, and the like, is that the first and second features are either in direct contact or in indirect contact through an intervening medium. Moreover, a first feature being "above," "over" and "on" a second feature may be a first feature being directly above or obliquely above the second feature, or simply indicating that the first feature is level higher than the second feature. The first feature being "under", "below" and "beneath" the second feature may be the first feature being directly under or obliquely below the second feature, or simply indicating that the first feature is less level than the second feature.
It will be understood that if an element is referred to as being "fixed" or "disposed" on another element, it can be directly on the other element or intervening elements may also be present. If an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and the like as used herein, if any, are for descriptive purposes only and do not represent a unique embodiment.
The immunoassay technology has been applied more and more in recent years due to the advantages of high sensitivity, good specificity, wide linear range, high throughput, strong platform expansibility, abundant menu of measurable items, etc. In the detection process of immunoassay, the sample carried in the reaction cup needs to be taken, and after the sample finishes the corresponding reaction, the sample is cleaned and separated. However, in the related art, the operations of sample loading, cleaning and separating are complicated, so that the whole immunoassay detection process is time-consuming and labor-consuming, and the immunoassay system is complex in structure and high in cost. Based on the above problems, the present application provides an automatic pipetting method.
Referring to fig. 1, fig. 1 is a schematic flow chart of an automatic pipetting method according to some embodiments of the application. Some embodiments of the application provide an automated pipetting method for immunoassays comprising:
s10: the cuvette 1100 is grasped by the gripper apparatus 100 and moved into the loading site 210 of the magnetic collection apparatus 200.
S20: a first preset reaction liquid is injected into the reaction cup 1100 through the sampling needle device 300.
S30: the sampling needle device 300 is controlled to move to the washing tub 1000 and the sampling needle 310 of the sampling needle device 300 is subjected to a washing operation.
S40: a second preset reaction liquid is injected into the reaction cup 1100 through the first liquid injection apparatus 500.
S50: the waste liquid in the cuvette 1100 is sucked out through the sampling needle 310 after the washing operation.
When the automatic pipetting method is used in an immunoassay system to perform sample loading and cleaning separation, the cuvette 1100 is gripped and moved to the loading position 210 of the magnetic collection device 200 by the gripper device 100, and then a first preset reaction solution is injected into the cuvette 1100 by the sampling needle device 300, where the first preset reaction solution may be a preset reagent in a sample and/or a kit in a sample tube. After the first preset reaction liquid is injected, the sampling needle 310 of the sampling needle device 300 is subjected to a washing operation. And a second preset reaction liquid, which may be a cleaning separation buffer, is injected into the reaction cup 1100 through the first liquid injection device 500. Finally, the waste liquid in the reaction cup 1100 is sucked out through the sampling needle 310 after the cleaning operation, and the waste liquid is the unbound part of the reagent which needs to be removed after the reaction cup 1100 is cleaned. According to the automatic pipetting method provided by the application, under the cooperative cooperation of the gripper device 100, the magnetic collection device 200, the sampling needle device 300, the first liquid injection device 500 and the cleaning pool 1000, sample adding and cleaning separation operations can be completed through the sampling needle device 300 and the first liquid injection device 500, so that sample and/or preset reagents are easy to sample adding and cleaning separation operations; and no separate sample sucking and discharging mechanism and reagent sucking and discharging mechanism are required to be additionally arranged; the sample, the reagent or the cleaning buffer solution is not required to be injected through the liquid injection mechanism, and the waste liquid in the reaction cup 1100 is not required to be sucked and discharged by the independent waste liquid sucking mechanism, so that the automatic liquid transferring device of the immunoassay system is simpler in structure, smaller in size and lower in manufacturing cost in the preparation process.
It should be noted that, the order of the step S30 and the step S40 is not particularly limited, and the step S30 may be executed first, and then the step S40 may be executed; the step S40 may be executed first, and then the step S30 may be executed; of course, the step S30 and the step S40 may be performed simultaneously.
It should be noted that the first preset reaction solution may be a sample in the sample tube and/or a preset reagent in the kit. The second preset reaction liquid may be a wash separation buffer for wash separation. Of course, in other embodiments, the first preset reaction solution and the second preset reaction solution may be other reagents, which are not limited in particular.
The automatic pipetting method is specifically described below. In some of these embodiments, step S20: the injection of the first preset reaction liquid into the reaction cup 1100 through the sampling needle device 300 specifically includes:
The magnetic collection device 200 is controlled to move in a first direction, specifically, the xx' direction in fig. 2 and 3, so that the sample application site 210 is located at a first preset position. By controlling the magnetic collection device 200 to move along the xx' direction in fig. 2 and 3, the sample loading position 210 on the magnetic collection device 200 is located at the first preset position, that is, the moving position, so that the subsequent sample loading operation on the first preset reaction solution in the reaction cup 1100 is convenient.
The sampling needle device 300 is controlled to move to the reagent sample loading device 600 and aspirate the first preset reaction solution through the sampling needle 310. When the sampling needle device 300 is required to suck the first preset reaction solution, the sampling needle device 300 is controlled to move to the reagent sample loading device 600 along the xx ', yy ' and zz ' directions in fig. 2, and the first preset reaction solution is sucked through the sampling needle 310, where the first preset reaction solution may be a sample in a sample tube and/or a preset reagent in a reagent kit, or may be other reagents, which is not limited in particular.
The sampling needle 310 for sucking the first preset reaction liquid is controlled to move to the magnetic collection device 200, and the first preset reaction liquid is injected into the reaction cup 1100 through the sampling needle 310. After the sampling needle 310 sucks the first preset reaction liquid, the sampling needle device 300 is moved to the magnetic collection device 200, and the first preset reaction liquid is injected into the reaction cup 1100 through the sampling needle 310.
In some of these embodiments, step S30: the control of the movement of the sampling needle device 300 to the cleaning tank 1000 and the cleaning operation of the sampling needle 310 of the sampling needle device 300 specifically includes: controlling the movement of the sampling needle 310 to move the sampling needle 310 into the washing tub 1000; the inner and outer walls of the sampling needle 310 are subjected to a cleaning operation by the cleaning bath 1000. When the sampling needle device 300 is moved to the washing cell 1000, the sampling needle 310 is controlled to move in the zz' direction in fig. 2, so that the sampling needle 310 moves into the washing cell 1000; then cleaning operation is carried out on the inner wall and the outer wall of the sampling needle 310 through a cleaning pump, an inner wall cleaning valve and a vacuum pump in the cleaning pool 1000, so that reagent sucking operation of the sampling needle 310 at the next time is convenient, and the possibility of polluting the reagent sucking at the next time is reduced.
In some embodiments, the step of injecting the second preset reaction liquid into the reaction cup 1100 by the first liquid injection apparatus 500 further includes: the cuvette 1100 is grasped by the gripper device 100 and moved into the incubation aperture 710 of the incubation device 700; performing incubation operation on a first preset reaction liquid in the reaction cup 1100 through the incubation device 700; the cuvette 1100, which has completed the incubation operation, is grasped by the gripper device 100 and moved into the collection station 220 of the magnetic collection device 200. After the first preset reaction solution is injected into the reaction cup 1100 and before the second reagent is injected, the reaction cup 1100 is grabbed and moved into the incubation hole 710 of the incubation device 700 by the gripper device 100, and the incubation operation is performed on the first preset reaction solution in the reaction cup 1100 by the incubation device 700, and after the incubation operation is completed, the reaction cup 1100 after the incubation operation is grabbed and moved into the collection position 220 of the magnetic collection device 200 by the gripper device 100, so that the subsequent cleaning and separation operations are facilitated.
It should be noted that, after the incubation operation is performed on the first preset reaction solution in the reaction cup 1100, the reaction cup 1100 after the incubation operation is grabbed and moved onto the collection position 220 of the magnetic collection device 200 by the gripper device 100, and then the second preset reaction solution is injected into the reaction cup 1100 by the first injection device 500, so that the reaction mixture after the incubation reaction is washed and separated in the reaction cup 1100.
It should be noted that, the cleaning and separating means that the reactant in the reaction cup 1100 after completing the incubation reaction collects the magnetic beads and the magnetic bead complexes (the magnetic beads are abbreviated as "magnetic beads" in the present application) on the wall of the cup under the action of the magnetic field, and finally removes the portion of the reactant body not bound to the magnetic beads.
It should be noted that, the magnetic beads in the reaction cup 1100 are added when the first preset reaction liquid is added to the reaction cup 1100, that is, the magnetic beads are mixed in the first preset reaction liquid.
In some of these embodiments, step S50: the method for sucking out the waste liquid in the reaction cup 1100 through the sampling needle device 300 after the cleaning operation specifically comprises the following steps:
Controlling the magnetic collection device 200 to move in a first direction to move the cuvette 1100 at the collection site 220 to a first preset position; when the incubation operation is completed by the first preset reaction liquid in the reaction cup 1100 and the second preset reaction liquid is added into the reaction cup 1100, the magnetic collection device 200 is controlled to move along the first direction, so that the reaction cup 1100 at the collection position 220 moves to the first preset position, that is, the liquid moving position, thereby facilitating the subsequent absorption of the waste liquid in the reaction cup 1100 by the sampling needle 310.
Performing magnetic collection operation on a second preset reaction liquid in the reaction cup 1100 through the magnetic collection device 200; when the cuvette 1100 at the collection site 220 is moved to the first preset position, the magnetic collection operation of the reactants in the cuvette 1100 after the incubation reaction is performed by the magnet at the outer periphery of the collection site 220. The magnetic collection operation is to collect and collect paramagnetic beads in the reaction cup 1100 under the action of the magnetic field of the magnet on the inner wall of the reaction cup 1100 so as to separate the magnetic beads from reactants which are not combined with the magnetic beads.
The waste liquid in the cuvette 1100 after the magnetic collection operation is sucked out through the sampling needle 310 after the washing operation. After the magnetic collection operation is performed on the second preset reaction liquid in the reaction cup 1100, the waste liquid in the reaction cup 1100 after the magnetic collection operation is sucked out through the sampling needle 310 after the cleaning operation, so that the cleaning and separation operation on the liquid in the reaction cup 1100 is realized.
In some of these embodiments, after the step of sucking out the waste liquid in the cuvette 1100 after the magnetic collection operation by the sampling needle 310 after the washing operation, it further includes: the sampling needle device 300 is controlled to move to the washing tub 1000 and the sampling needle 310 of the sampling needle device 300 is subjected to a secondary washing operation. When the sampling needle device 300 is moved to the washing tank 1000 after the waste liquid in the reaction cup 1100 is sucked out through the sampling needle 310, the sampling needle 310 is controlled to move in the zz' direction in fig. 2 so that the sampling needle 310 moves into the washing tank 1000; then, the inner wall and the outer wall of the sampling needle 310 are subjected to secondary cleaning operation by the cleaning pump in the cleaning tank 1000, the inner wall cleaning valve and the vacuum pump, so that the reagent sucking operation of the sampling needle 310 at the next time is facilitated, and the possibility of polluting the reagent sucking at the next time is reduced.
The present application also provides an automatic pipetting device, please refer to fig. 2 and 3, and fig. 2 is a schematic diagram showing an automatic pipetting device according to some embodiments of the present application mounted to an immunoassay system in combination with fig. 4 and 5. Fig. 3 shows a top view of the immunoassay system shown in fig. 2. Fig. 4 shows a schematic diagram of a magnetic collection device 200 in the immunoassay system shown in fig. 3. Fig. 5 shows a schematic diagram of a sampling needle device 300 in the immunoassay system shown in fig. 3. An automatic pipetting device according to an embodiment of the application includes a controller (not shown), a magnetic collection device 200, a gripper device 100, a sampling needle device 300, a wash basin 1000, and a first pipetting device 500. The magnetic collection device 200 is electrically connected with the controller, and the magnetic collection device 200 is provided with a sample adding position 210 and a collection position 220, wherein the sample adding position 210 and the collection position 220 are used for bearing the reaction cup 1100; the gripper device 100 is electrically connected with the controller, the gripper device 100 can be close to or far away from the magnetic collection device 200, and the gripper device 100 is used for grabbing and moving the reaction cup 1100 into or out of the sample adding position 210 or the collection position 220; the sampling needle device 300 is electrically connected with the controller, the sampling needle device 300 can be close to or far away from the magnetic collection device 200, the sampling needle device 300 comprises a sampling needle 310, and the sampling needle 310 is used for sucking a first preset reaction liquid and discharging the first preset reaction liquid into the reaction cup 1100; and the sampling needle 310 is also used for sucking out the waste liquid in the reaction cup 1100; the cleaning tank 1000 is used for performing a cleaning operation on the sampling needle 310; the liquid injection device is electrically connected to the controller, and the first liquid injection device 500 is used for injecting the second preset reaction liquid into the reaction cup 1100 located in the collection position 220.
When the automatic pipetting device is used in an immunoassay system to perform sample loading and washing separation, the cuvette 1100 is gripped and moved to the loading position 210 of the magnetic collection device 200 by the gripper device 100, and then a first preset reaction solution is injected into the cuvette 1100 by the sampling needle device 300, where the first preset reaction solution may be a sample in a sample tube and/or a preset reagent in a kit. After the first preset reaction liquid is injected, the sampling needle 310 of the sampling needle device 300 is subjected to a washing operation. And a second preset reaction liquid, which may be a cleaning separation buffer, is injected into the reaction cup 1100 through the first liquid injection device 500. Finally, the waste liquid in the reaction cup 1100 is sucked out through the sampling needle 310 after the cleaning operation, and the waste liquid is the unbound part of the reagent which needs to be removed after the reaction cup 1100 is cleaned. The automatic pipetting device provided by the application enables sample adding and cleaning separation operations to be completed through the sampling needle device 300 and the first pipetting device 500 under the cooperative cooperation of the gripper device 100, the magnetic collecting device 200, the sampling needle device 300, the first pipetting device 500 and the cleaning pool 1000, so that a separate sample sucking and discharging mechanism and a separate reagent sucking and discharging mechanism are not required to be additionally arranged for sucking and discharging waste liquid in the reaction cup 1100, and the automatic pipetting device is simpler in structure, smaller in size and lower in manufacturing cost in the preparation process.
In some of these embodiments, the controller is configured to perform control operations comprising: the control gripper device 100 grips and moves the reaction cup 1100 to the sample adding position 210; controlling the sampling needle device 300 to inject a first preset reaction liquid into the reaction cup 1100; controlling the sampling needle device 300 to move to the cleaning tank 1000 and performing a cleaning operation on the sampling needle 310; controlling the first liquid injection device 500 to inject a second preset reaction liquid into the reaction cup 1100; the sampling needle device 300 after the washing operation is controlled to suck out the waste liquid in the reaction cup 1100. Through above-mentioned operation of controller control to make this automatic pipetting device when carrying out the pipetting operation to reagent, can be more automatic, efficiency is higher.
Referring to fig. 3, in some embodiments, the automatic pipetting device further includes a reagent sample loading apparatus 600, the reagent sample loading apparatus 600 includes a first reagent carrier 610, and the first reagent carrier 610 is configured to carry a first preset reaction solution; the controller controls the approaching or separating of the sampling needle device 300 with respect to the reagent sample loading device 600 and the aspiration of the first preset reaction solution through the sampling needle 310 into the first reagent carrier 610. The first preset reaction liquid is carried by the first reagent carrier 610 and the controller is caused to control the sampling needle device 300 to approach or depart from the reagent sample loading device 600 in the xx ', yy ' and zz ' directions in fig. 2, so that the sampling needle 310 sucks the first preset reaction liquid in the first reagent carrier 610.
Referring to fig. 6, fig. 6 shows a schematic diagram of a fluid circuit assembly 800 of a sampling needle device 300 in the immunoassay system shown in fig. 3. In some of these embodiments, the sampling needle device 300 further comprises a fluid path assembly 800; the liquid path assembly 800 is connected with the controller, and the liquid path assembly 800 is connected with the sampling needle 310, and the liquid path assembly 800 is used for enabling the sampling needle 310 to suck or discharge the first preset reaction liquid or the waste liquid. The liquid path assembly 800 is controlled by the controller, so that the sampling needle 310 sucks or discharges the first preset reaction liquid or waste liquid under the control of the preset program of the controller, and the whole process is high in automation and difficult to be disordered.
Referring to fig. 6, in some embodiments, a fluid circuit assembly 800 includes a syringe 810 and a first control valve 820. The syringe 810 includes a body 811 and a plunger 812; the body 811 is provided with a sliding cavity 8111, the plunger 812 is connected with the controller, and the plunger 812 is at least partially accommodated in the sliding cavity 8111 and is in sliding connection with the cavity wall of the sliding cavity 8111; the sliding cavity 8111 is provided with a first interface 8112 and a second interface 8113, and the first interface 8112 is communicated with the sampling needle 310; the first control valve 820 is connected with the controller, and the first control valve 820 is communicated with the second interface 8113; when the sampling needle 310 sucks the first preset reaction liquid or waste liquid, the first control valve 820 is closed, and the plunger 812 moves toward the side away from the bottom wall of the sliding chamber 8111, so that the air pressure in the sliding chamber 8111 is reduced; when the sampling needle 310 discharges the first preset reaction solution or waste liquid, the first control valve 820 is closed, and the plunger 812 moves toward the side close to the bottom wall of the sliding chamber 8111, so that the air pressure in the sliding chamber 8111 increases.
When the sampling needle 310 is required to suck the first preset reaction liquid or waste liquid, the controller controls the first control valve 820 to be closed at this time, and causes the controller to control the plunger 812 to move toward a side away from the bottom wall of the sliding cavity 8111, that is, from m to m' in fig. 6, so that the air pressure in the sliding cavity 8111 is reduced, and the sampling needle 310 is enabled to suck the first preset reaction liquid or waste liquid under the action of the atmospheric pressure. When the sampling needle 310 needs to discharge the sucked first preset reaction solution or waste solution, the controller controls the plunger 812 to move toward the side close to the bottom wall of the sliding chamber 8111, that is, from m' to m in fig. 6, so that the air pressure in the sliding chamber 8111 is increased, and the sampling needle 310 discharges the first preset reaction solution or waste solution under the action of the atmospheric pressure. In one embodiment, the first control valve 820 is a first solenoid valve.
Referring to fig. 6, in some embodiments, the first liquid injection apparatus 500 includes a second reagent carrier 510, where the second reagent carrier 510 is used to carry a second preset reaction liquid; the fluid circuit assembly 800 further includes a second control valve 830, the second control valve 830 being a three-way valve; second control valve 830 is connected between first interface 8112 and sampling needle 310; the second control valve 830 is also in communication with the second reagent carrier 510; when the first filling device 500 fills the reaction cup 1100 located in the collection position 220 with the second preset reaction liquid, the first control valve 820 is closed, the second control valve 830 is opened, and the plunger 812 moves toward the side close to the bottom wall of the sliding chamber 8111. When it is desired to inject the second preset reaction liquid into the reaction cup 1100 through the first liquid injection apparatus 500, at this time, the first control valve 820 is closed and the second control valve 830 is opened, and then the controller controls the plunger 812 to move toward one side close to the bottom wall of the sliding chamber 8111, that is, from m' toward m in fig. 6, so that the second preset reaction liquid flowing into the sliding chamber 8111 from the second reagent carrier 510 is injected into the reaction cup 1100. In one embodiment, the second control valve 830 is a second solenoid valve.
Referring to fig. 6, in some embodiments, the first control valve 820 is a three-way valve, one of which is further in communication with the wash tank 1000, and the other of which is in communication with the second reagent carrier 510, so that the second predetermined reaction solution, i.e., the wash separation buffer, is in communication with the wash tank 1000 by controlling the on-off interface of the first control valve 820, thereby performing a wash operation on the inner and outer walls of the sampling needle 310.
Referring to fig. 6, in one embodiment, the normally closed end of the first control valve 820 is connected to the second port 8113 of the body 811, and the normally open end of the first control valve 820 is connected to the purge tank 1000. When the first control valve 820 is de-energized, the body 811 is disconnected from the wash tank 1000, forming a closed circuit. The common end of the second control valve 830 is connected to the first port 8112 of the body 811, the normally closed end of the second control valve 830 is connected to the injection mechanism 870 of the second preset reaction liquid, and the normally open end of the second control valve 830 is connected to the sampling needle 310.
When the sampling needle 310 is required to suck the waste liquid in the reaction cup 1100, the sampling needle 310 is moved to the bottom of the reaction cup 1100 at this time, and the plunger 812 is moved toward the side away from the bottom wall of the sliding chamber 8111, so that the air pressure of the sliding chamber 8111 is reduced and a vacuum is formed, and at the same time, since the first control valve 820 is closed, the restoration of the inside of the sliding chamber 8111 to the atmospheric pressure requires the suction of the waste liquid from the port of the sampling needle 310, thereby realizing the suction of the waste liquid in the reaction cup 1100 into the inside of the sampling needle 310.
When the waste liquid is sucked into the sampling needle 310, the sampling needle 310 is transferred into the cleaning tank 1000, and the waste liquid in the sampling needle 310 is discharged and the inner and outer walls are cleaned, so that the sampling needle 310 is cleaned.
When the sampling needle 310 is required to suck the first preset reaction liquid, the sampling needle 310 is moved above the suction level and is lowered into the first reagent carrier 610 carrying the first preset reaction liquid, and the control plunger 812 is moved towards the side far away from the bottom wall of the sliding cavity 8111, so that the air pressure of the sliding cavity 8111 is reduced and a vacuum is formed, and meanwhile, the first control valve 820 is closed, so that the first preset reaction liquid is required to be sucked from the port of the sampling needle 310 in the sliding cavity 8111, and the first preset reaction liquid in the first reagent carrier 610 is sucked into the interior of the sampling needle 310. Alternatively, the first preset reaction solution may be a sample, or may be a reagent. When the sample or reagent is sucked up by the sampling needle 310, the sampling needle device 300 is moved to the magnetic collection device 200, and the sampling needle 310 is lowered into the reaction cup 1100, and the control plunger 812 is moved toward the side close to the bottom wall of the sliding chamber 8111, that is, from m' toward m in fig. 6, so that the reagent or sample is injected into the reaction cup 1100.
When the second preset reaction solution is required to be injected into the reaction cup 1100, the magnetic collection device 200 is controlled to move along the first direction to move the reaction cup 1100 to the first injection level, after the antigen-antibody or the cleaning solution in the reaction cup 1100 is discharged through the sampling needle 310, the second control valve 830 is opened, the first control valve 820 is closed, the plunger 812 moves toward the side close to the bottom wall of the sliding cavity 8111, that is, moves from m' to m in fig. 6, and the cleaning buffer solution is discharged into the reaction cup 1100.
Referring to fig. 6, in some embodiments, the bottom wall of the washing tank 1000 is further connected to a washing waste liquid carrier 840, and when the inner and outer walls of the sampling needle 310 are washed, waste liquid generated during the washing process flows into the washing waste liquid carrier 840.
Referring to fig. 6, in some embodiments, the fluid circuit assembly 800 further comprises a substrate carrier 860 and a substrate injector 850. The substrate carrier 860 and the substrate injector 850 are connected by a control valve, and the substrate injector 850 is capable of injecting the substrate of the substrate carrier 860 into the cuvette 1100.
Referring to fig. 6, in some embodiments, the liquid path assembly 800 further includes a third reagent carrier 520, the third reagent carrier 520 is in communication with the second reagent carrier 510, and the third reagent carrier 520 also carries a second predetermined reaction liquid therein. Thereby replenishing the second preset reaction liquid into the second reagent carrier 510 through the third reagent carrier 520.
Referring to fig. 2 and 3, the present application also provides an immunoassay system, comprising the automatic pipetting device according to any one of claims 7 to 12. At least one of the technical effects described above can be achieved.
It should be understood that, in the embodiment of the present application, at least a part of the steps in the preparation method may include a plurality of steps or a plurality of stages, which are not necessarily performed at the same time, but may be performed at different times, and the order of performing the steps or stages is not necessarily performed sequentially, but may be performed alternately or alternately with other steps or at least a part of the steps or stages in other steps.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the application, which are described in detail and are not to be construed as limiting the scope of the claims. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the application, which are all within the scope of the application. Accordingly, the scope of protection of the present application is to be determined by the appended claims.
Claims (13)
1. An automated pipetting method for use in immunoassays, the automated pipetting method comprising:
grabbing and moving the reaction cup to a sample adding position of the magnetic collecting device through a grabbing device;
injecting a first preset reaction liquid into the reaction cup through sampling needle equipment;
Controlling the sampling needle equipment to move to a cleaning pool, and cleaning the sampling needle of the sampling needle equipment;
Injecting a second preset reaction liquid into the reaction cup through a first liquid injection device;
And sucking out the waste liquid in the reaction cup through the sampling needle after the cleaning operation.
2. The automatic pipetting method as recited in claim 1, wherein the step of injecting the first predetermined reaction liquid into the reaction cup through the sampling needle device comprises:
controlling the magnetic collection device to move along a first direction so that the sample adding position is positioned at a first preset position;
Controlling the sampling needle device to move to the reagent sample loading device, and sucking the first preset reaction liquid through the sampling needle;
And controlling a sampling needle for sucking the first preset reaction liquid to move to the magnetic collection device, and injecting the first preset reaction liquid into the reaction cup through the sampling needle.
3. The automatic pipetting method according to claim 1, wherein the step of controlling the sampling needle device to move to a wash basin and performing a wash operation on the sampling needle of the sampling needle device comprises:
controlling the sampling needle to move so as to enable the sampling needle to move into the cleaning pool;
and cleaning the inner wall and the outer wall of the sampling needle through the cleaning pool.
4. The automated pipetting method of claim 1 wherein the step of injecting a second predetermined reaction liquid into the reaction cup by the first liquid injection apparatus is preceded by the step of:
Grabbing and moving the reaction cup into an incubation hole of an incubation device through the gripper device;
Performing incubation operation on a first preset reaction liquid in the reaction cup through the incubation equipment;
And grabbing and moving the reaction cup which completes the incubation operation to a collection position of the magnetic collection device through the grabbing device.
5. The automatic pipetting method as recited in claim 1 wherein the step of aspirating the waste fluid from the cuvette through the needle apparatus after the washing operation specifically comprises:
Controlling the magnetic collection device to move along a first direction so as to enable the reaction cup at the collection position of the magnetic collection device to move to a first preset position;
performing magnetic collection operation on the second preset reaction liquid in the reaction cup through the magnetic collection equipment;
And sucking out the waste liquid in the reaction cup after the magnetic collection operation through the sampling needle after the cleaning operation.
6. The automatic pipetting method as recited in claim 5, further comprising, after the step of sucking out the waste liquid in the cuvette after the magnetic collection operation by the sampling needle after the washing operation:
And controlling the sampling needle equipment to move to the cleaning pool, and performing secondary cleaning operation on the sampling needle of the sampling needle equipment.
7. An automatic pipetting device, comprising:
a controller;
The magnetic collection device is electrically connected with the controller and is provided with a sample adding position and a collection position, and the sample adding position and the collection position are used for bearing a reaction cup;
The gripper device is electrically connected with the controller, can be close to or far away from the magnetic collection device and is used for grabbing and moving the reaction cup into or out of the sample adding position or the collection position;
The sampling needle device is electrically connected with the controller, can be close to or far away from the magnetic collecting device, and comprises a sampling needle for sucking a first preset reaction liquid and discharging the first preset reaction liquid into the reaction cup; the sampling needle is also used for sucking out waste liquid in the reaction cup;
The cleaning pool is used for cleaning the sampling needle;
The first liquid injection device is electrically connected with the controller and is used for injecting second preset reaction liquid into the reaction cup located in the collecting position.
8. The automatic pipetting device of claim 7, wherein the controller is configured to perform control operations comprising:
controlling the gripper equipment to grasp and move the reaction cup to the sample adding position;
controlling the sampling needle device to inject the first preset reaction liquid into the reaction cup;
Controlling the sampling needle equipment to move to the cleaning pool and cleaning the sampling needle;
Controlling the first liquid injection equipment to inject a second preset reaction liquid into the reaction cup;
and controlling the sampling needle equipment after the cleaning operation to suck out the waste liquid in the reaction cup.
9. The automated pipetting device of claim 7, further comprising a reagent sample loading apparatus comprising a first reagent carrier for carrying a first preset reaction liquid;
The controller controls the sampling needle device to approach or depart from the reagent sample loading device and aspirate the first preset reaction liquid through the sampling needle in the first reagent carrier.
10. The automated pipetting device of claim 7 wherein the sampling needle apparatus further comprises a fluid path assembly;
The liquid path component is connected with the controller, and the liquid path component is connected with the sampling needle, and the liquid path component is used for enabling the sampling needle to suck or discharge the first preset reaction liquid or the waste liquid.
11. The automated pipetting device of claim 10, wherein the liquid path assembly comprises:
A syringe comprising a body and a plunger; the body is provided with a sliding cavity, the plunger is connected with the controller, and the plunger is at least partially accommodated in the sliding cavity and is in sliding connection with the cavity wall of the sliding cavity; a first interface and a second interface are constructed on the sliding cavity, and the first interface is communicated with the sampling needle;
The first control valve is connected with the controller and is communicated with the second interface;
When the sampling needle sucks the first preset reaction liquid or the waste liquid, the first control valve is closed, and the plunger moves towards one side away from the bottom wall of the sliding cavity so as to reduce the air pressure in the sliding cavity;
When the sampling needle discharges the first preset reaction liquid or the waste liquid, the first control valve is closed, and the plunger moves towards one side close to the bottom wall of the sliding cavity so as to increase the air pressure in the sliding cavity.
12. The automated pipetting device of claim 11 wherein the first pipetting apparatus comprises a second reagent carrier for carrying the second preset reaction liquid;
The liquid path assembly further comprises a second control valve, the second control valve is connected with the controller, and the second control valve is a three-way valve; the second control valve is connected between the first interface and the sampling needle; the second control valve is also in communication with the second reagent carrier;
when the first liquid injection device injects second preset reaction liquid into the reaction cup in the collecting position, the first control valve is closed, the second control valve is opened, and the plunger moves towards one side close to the bottom wall of the sliding cavity.
13. An immunoassay system comprising the automated pipetting device of any one of claims 7-12.
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