CN111122886A

CN111122886A - Dilution method, dilution device, and immunoassay analyzer

Info

Publication number: CN111122886A
Application number: CN201811277653.9A
Authority: CN
Inventors: 张震
Original assignee: Shenzhen Increcare Biotech Co Ltd
Current assignee: Shenzhen Increcare Biotech Co Ltd
Priority date: 2018-10-30
Filing date: 2018-10-30
Publication date: 2020-05-08
Anticipated expiration: 2038-10-30
Also published as: CN111122886B

Abstract

A method of dilution comprising the steps of: moving the blending assembly (120) carrying the first reactor to a first station (11), and adding a sample into the first reactor; moving the first reactor containing the sample to a second station (12), and adding a diluent into the first reactor; mixing the sample and the diluent in the first reactor to form a diluted sample; moving the second reactor to the blending component (120) again and moving the second reactor to the first station (11), and adding a part of the diluted sample in the first reactor into the second reactor; moving the blending assembly (120) to a second station (12) and adding the reagent component to a second reactor; and mixing the diluted sample and the reagent components in the second reactor uniformly.

Description

Dilution method, dilution device, and immunoassay analyzer

Technical Field

The invention relates to the technical field of in-vitro diagnosis, in particular to a diluting method, a diluting device and an immunoassay analyzer comprising the diluting device.

Background

The full-automatic immunoassay analyzer can perform quantitative or qualitative detection on target analysis substances such as antibodies and antigens contained in a sample to be detected such as blood, and generally, after a sample to be detected and a reagent (or called reactant) are added into an empty reactor, and are subjected to steps of uniform mixing, incubation, cleaning and separation (Bound-free, or BF separation, which is sometimes referred to as cleaning) and the like, a signal reagent is added into the reactor to measure optical signals or electric signals, so that the measurement and analysis of the target analysis substances contained in the sample to be detected are realized.

An important parameter for measuring the working efficiency of an immunoassay analyzer is the test throughput, which can be understood as the number of test results that the immunoassay analyzer can report in a unit time, i.e. for the number of reactors containing the target analyte to be measured, the greater the total number of reactors measured in a unit time, the higher the test throughput of the immunoassay analyzer. Because the reaction mode and the test flow of the analysis project are usually different, the test flux of the immunoassay analyzer is not constant, the maximum test flux is usually taken as the measurement standard of the test speed of the immunoassay analyzer, and the test flux refers to the maximum test flux of the immunoassay analyzer unless otherwise specified for convenience of description. Considering the immunoassay instrument as a flow line, if there are N reactors containing target analytes in a unit time that have been measured and leave the flow line, and to ensure that the test is performed continuously and reliably at maximum throughput, N empty reactors must enter the flow line at the same time, i.e., the flow rate of the reactors at the inlet of the flow line (inlet flow rate) is equal to the flow rate at the outlet (outlet flow rate). Similarly, in order to ensure seamless and continuous connection of the whole assembly line, the flow of the reactor in each link in the middle of the assembly line should be equal to the inlet flow and the outlet flow, i.e. the flow of each part of the assembly line is equal.

Generally, for some specific test analysis, before the sample and the reagent are mixed, the sample must be diluted, however, the dilution process takes a long time, so that the flow rate of the reactor in the dilution process is low, which becomes a bottleneck and a short plate affecting the working efficiency, and thus the immunoassay analyzer is difficult to meet the requirement of high test throughput.

Disclosure of Invention

The invention solves a technical problem of how to improve the work efficiency of dilution.

A method of dilution comprising the steps of:

carrying the first reactor by the blending component, moving the first reactor to a first station, and adding a sample into the first reactor;

moving the first reactor containing the sample to a second station, and adding diluent into the first reactor;

mixing the sample and the diluent in the first reactor to form a diluted sample;

moving the second reactor to the blending component again, moving the second reactor to the first station again, and adding a part of the diluted sample in the first reactor into the second reactor;

moving the blending assembly to a second station, and adding reagent components into a second reactor; and

the diluted sample and reagent components in the second reactor are mixed well.

In one embodiment, the homogenizing assembly is cyclically reciprocated between an initial station, in which the first and second reactors are moved into and out of the homogenizing assembly, a first station, and a second station.

In one embodiment, the initial station, the first station and the second station are arranged in a same line, and the initial station is arranged between the first station and the second station.

In one embodiment, both the diluent and reagent components are placed on the same storage unit.

In one embodiment, after a portion of the diluted sample is added to the second reactor, the first reactor is removed from the homogenizing assembly and discarded.

In one embodiment, the blending component blends the sample and the diluent in the first reactor and the diluted sample and the reagent components in the second reactor by non-contact eccentric oscillation.

In one embodiment, the number of blending assemblies is at least two.

A dilution apparatus having a first station and a second station, comprising:

a transport assembly;

the blending assembly is arranged on the conveying assembly and used for bearing the first reactor and the second reactor and blending the sample, the diluent, the diluted sample and the reagent components in the first reactor and the second reactor, and the conveying assembly can drive the blending assembly to move between a first station and a second station; and

the liquid transferring assembly is used for adding the sample into the first reactor when the blending assembly moves to the first station; when the blending assembly moves to the second station, the liquid-transfering assembly adds the diluent into the first reactor; when the blending assembly moves to the first station again, the liquid-transferring assembly adds a part of the diluted sample obtained by blending the diluent and the sample into the second reactor from the first reactor, and when the blending assembly moves to the second station again, the liquid-transferring assembly adds the reagent component into the second reactor containing the diluted sample.

In one embodiment, the pipetting assembly comprises a sample pipetting unit for pipetting a sample and a diluted sample and a reagent pipetting unit for pipetting a dilution and reagent components.

In one embodiment, the number of the blending assemblies is at least two.

In one embodiment, the number of the conveying assemblies is one, and the conveying assemblies synchronously drive all the blending assemblies to circularly reciprocate between the first station and the second station.

In one embodiment, the number of the conveying assemblies is two, each conveying assembly is provided with the blending assembly for bearing the reactor, and each conveying assembly drives the blending assembly to circularly reciprocate between the first station and the second station.

An immunoassay analyzer comprising any of the above dilution devices.

One technical effect of one embodiment of the invention is that: through bearing first reactor and second reactor on same mixing subassembly, both separation distances of first reactor and second reactor are little, can provide the dilution sample from first reactor to the second reactor fast, improve dilution work efficiency on the basis that makes dilution device compact structure. Simultaneously, all add corresponding liquid in first station and two positions of second station department to each reactor, the mixing subassembly moves fast in the short distance, can improve work efficiency and reduce the motion control degree of difficulty of mixing subassembly.

Drawings

Fig. 1 is a schematic plan view of an immunoassay analyzer according to a first embodiment;

FIG. 2 is a schematic perspective view of the blending apparatus shown in FIG. 1;

FIG. 3 is a schematic plan view of an immunoassay analyzer according to a second embodiment;

FIG. 4 is a schematic perspective view of the blending apparatus shown in FIG. 3;

FIG. 5 is a block flow diagram of a tandem blending method according to an embodiment;

fig. 6 is a block flow diagram of a parallel blending method according to an embodiment;

FIG. 7 is a block flow diagram of a reagent pipetting method according to an exemplary embodiment;

FIG. 8 is a block flow diagram of a dilution method provided by an embodiment;

fig. 9 is a block flow diagram of an immunoassay method according to an embodiment.

Detailed Description

To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When 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 "inner", "outer", "left", "right" and the like as used herein are for illustrative purposes only and do not represent the only embodiments.

The incubation of the sample reagent (or reactant) refers to the process of antigen-antibody binding reaction or biotin-avidin binding reaction of the reactant in the reactor under a constant temperature environment before the reactor is cleaned (separated). The reagent and the analysis items are in a one-to-one correspondence relationship, that is, the specific reagents corresponding to different analysis items generally differ in terms of formula, reagent amount, component amount, and the like. According to different specific analysis items, the reagent generally comprises a plurality of components, such as common 2-5 components, including magnetic particles, enzyme labels, diluents, dissociation agents and other reagent components, for example, T4 reagent (thyroxine) comprises three components of magnetic particles, enzyme labels and dissociation agents. Depending on the reaction mode, a plurality of reagent components of one analysis item may be dispensed at one time or in a plurality of steps, and the step dispensing is defined as a first reagent, a second reagent, a third reagent, and the like in the order of dispensing. After the incubation is finished, washing and separating are carried out, wherein the washing and separating refers to a process of capturing a compound of the bound magnetic particles, the antigen and the labeled antibody by using a magnetic field, and simultaneously removing Free labeled antibody and other unreacted or bound components (which are convenient to express and are abbreviated as unbound components). After washing the separation, the signal reagent is dispensed, a signal incubation is carried out (typically for 1-6 minutes), and finally the amount of luminescence produced by the reaction of the labeling reagent with the signal reagent (referred to herein for convenience as the reactant signal) is measured. The signal reagent is used for measuring the generation of a signal (usually, a luminescence amount), and is usually one of general-purpose reagents, and corresponds to an analysis item in a "one-to-many" relationship, that is, the signal reagent is shared by different analysis items. The signal incubation refers to a process of adding a signal reagent into a reactor after washing and separation, and reacting for a period of time in a constant temperature environment to enhance signals. It should be noted that some luminescent systems do not require signal incubation due to the different specific components of the signal agent, and can be measured directly during or after dispensing of the signal agent. The signaling agent can be one or more, such as some signaling agents including a first signaling agent, a second signaling agent, and the like. In the immunoassay device, the antigen or antibody contained in the sample bound to the labeled reagent is quantitatively or qualitatively determined through the above-described procedure. Furthermore, the immunoassay analyzer is capable of analyzing a sample in accordance with several different analysis items.

A working period or cycle, or cycle for short, is the shortest time window that can recur cyclically during a test, which usually has a fixed time length, within which a certain number of process operations, tasks or work packages, etc., such as operations and tasks of liquid extraction, mixing, incubation, washing separation, measurement, etc., are performed in series or in parallel in a controlled order. Tasks of the same component in one cycle are usually executed in series, and tasks of different components in the same cycle can be executed in series or in parallel depending on whether actions of related components are dependent or not. All process operations performed in one cycle are performed only when needed and do not have to be repeated in another cycle. In particular, some process operations may be repeated in each cycle, while others may occur every two or more cycles. When a plurality of tests are carried out in succession, since each test is usually at a different stage of the test procedure, only some of the process operations are dedicated to carrying out one test and some of the other process operations are dedicated to carrying out the other test, i.e. in a single cycle, different process operations are respectively dedicated to different trials. Thus, testing is typically done in multiple cycles, with different process operations for conducting the testing occurring in different cycles. In order to improve the testing efficiency and throughput, for the components with speed bottlenecks, the component speed bottlenecks can be realized by increasing the number of the components and prolonging the periods of the components, so that the working periods of different components are not necessarily the same, namely, a plurality of parallel periods can exist in the same system, and the time lengths of the parallel periods are usually in a multiple relation, wherein the multiple is usually equal to the number of the same components. When there are two working cycles, called the first cycle and the second cycle respectively, for example, when the number of reagent pipetting units is N (N ≧ 2, which is a natural number), each reagent pipetting unit works in the first cycle, the length of the first cycle is N times of the second cycle, and the sequence of actions of the N reagent units is continuously "staggered in parallel" for the second cycle. The invention can realize high-flux immunity test, the typical second period length is 4-15 seconds, the corresponding test flux is 900-.

Referring to fig. 1 to 4, an immunoassay analyzer 10 according to an embodiment of the present invention includes a mixing device 100, a reaction device 200, a reagent supplying device 300, a sample supplying device 410, and a reactor supplying device 420. The reactor supply device 420 is used for providing a clean and vacant reactor 20, the sample supply device 410 is used for adding a sample into the vacant reactor 20, the reagent supply device 300 is used for adding a reagent into the reactor 20 containing the sample, the blending device 100 is used for performing blending processing on the reactor 20 containing the sample and the reagent, and the reaction device 200 is used for incubating, cleaning and measuring the sample and the reagent after the blending processing in the reactor 20.

In some embodiments, the reactor feed device 420 includes a feed silo, a sequencing mechanism, a feed chute, and a feed tray. The supply bin is used for storing clean and empty reactors 20, the supply bin can be located behind the reagent supply device 300, so that the space of the whole machine can be fully utilized, the structure of the immunoassay analyzer 10 becomes more compact, the sorting mechanism is used for sorting the reactors 20 which are randomly placed to be arranged in a certain order, the supply slide guides the sorted reactors 20 into the supply tray one by one, the supply tray is used for buffering the reactors 20 which are conveyed by the supply slide, the reactors 20 can be arranged at intervals along the circumferential direction of the supply tray, the supply tray can rotate around the central axis of the supply tray, so as to drive the reactors 20 to a designated position, the designated position can be defined as a reactor supply station, and the reactors 20 on the supply tray can be transferred to the blending device 100 from the reactor supply station.

In some embodiments, the sample supply device 410 includes a sample rack, a sample tube, a conveying track, a sample pipetting unit 411, and the like. The sample racks may be fitted with a conveying track, and the sample tubes are placed on the sample racks for holding samples, for example, five to about ten sample tubes may be placed on each sample rack. When the sample rack drives the sample tube to move to a designated position along the conveying track, the sample pipetting unit 411 pipettes the sample of the sample tube and adds the sample to the empty reactor 20. The sample pipetting unit 411 may be a steel needle or a disposable nozzle, and in order to achieve smooth suction of the sample, the sample pipetting unit 411 may perform vertical up-and-down movement, horizontal linear movement or horizontal rotation and other movement forms.

Referring to fig. 1 and fig. 2, in some embodiments, the blending device 100 is in series, the mixing device 101 includes a transportation component 110 and blending components 120, at least two blending components 120 are disposed on the transportation component 110, and the transportation component 110 can drive all the blending components 120 to move synchronously in the same direction, in short, all the blending components 120 are connected in series on one transportation component 110.

The transport assembly 110 includes a frame 111 and a conveyor disposed on the frame 111. The conveyor is used for driving all the blending components 120 to synchronously move towards the same direction, and can be composed of one or more of transmission forms or mechanisms such as a synchronous belt, a lead screw transmission, a gear rack and the like.

In some embodiments, the conveyor includes a motor 113, a driving pulley 114, a driven pulley 115, and a timing belt 112, wherein the motor 113 is used for driving the driving pulley 114 to rotate, the timing belt 112 is wound around the driving pulley 114 and the driven pulley 115, and when the motor 113 rotates, the driving pulley 114 and the driven pulley 115 drive the timing belt 112 to move.

Each blending assembly 120 includes a support 121, a driver 123, and a bearing platform 122, the support 121 is slidably disposed on the frame 111 and connected to the conveyor of the transport assembly 110. Specifically, can set up the slide rail on the frame 111, support 121 and slide rail cooperation, hold-in range 112 drives the support and slides along the direction that the slide rail extends, driver 123 installs on support 121 and is connected with plummer 122, plummer 122 is used for placing reactor 20, hold-in range 112 can drive support 121 on every mixing subassembly 120 all towards same direction motion, driver 123 can drive plummer 122 and produce eccentric oscillation, thereby make the reactant in the reactor 20 realize the mixing because of producing non-contact eccentric oscillation.

At least two receiving holes 122a may be formed in the susceptor 122, and the reactor 20 is inserted into the receiving holes 122a, so that the susceptor 122 can support the reactor 20. Of course, the receiving hole 122a may be replaced with a bracket or other solid structure as long as the reactor 20 can be placed on the susceptor 122.

When the number of the blending assemblies 120 is two, one of the blending assemblies 120 includes a first support 1211 and a first bearing platform 1221, and the other blending assembly 120 includes a second support 1212 and a second bearing platform 1222, the first support 1211 has a first mounting end 1211a, the second support 1212 has a second mounting end 1212a, and the second mounting end 1212a is disposed near the first mounting end 1211 a. The first carrier 1221 is positioned at the first mounting end 1211a and the second carrier 1222 is positioned at the second mounting end 1212 a. in short, the first carrier 1221 and the second carrier 1222 are positioned opposite to each other so that samples and reagents can be loaded into the reactors 20 on different carriers 122 at the designated locations.

Referring to fig. 5, when the serial blending apparatus 101 is used to blend the sample and the reagent, a serial blending method can be formed, and the serial blending method mainly includes the following steps:

s510, providing at least two blending assemblies 120 for bearing the reactor 20, and synchronously driving the blending assemblies 120 to circularly reciprocate between a first station 11 and a second station 12 by adopting the same conveying assembly 110; that is, the timing belt 112 drives all the carriers 122 to move between the first station 11 and the second station 12.

And S520, adding a sample into the reactor 20 at the first station 11, adding a reagent into the reactor 20 at the second station 12, and uniformly mixing the sample and the reagent in the reactor 20. When the synchronous belt 112 drives the bearing platform 122 to move to the first station 11, the synchronous belt 112 stops moving, and the sample pipetting unit 411 sucks the sample and adds the sample into one of the reactors 20 as the sample pipetting unit 411 is arranged near the first station 11; after the sample is added, when the timing belt 112 drives the carrier 122 to move to the second station 12, the timing belt 112 stops moving, and the reagent can be added to the reactor 20 containing the sample by the reagent pipetting unit 310 in the reagent supplying apparatus 300. After the sample and the reagent are added into the reactor 20, the driver 123 may drive the bearing platform 122 to generate eccentric oscillation, so as to uniformly mix the sample and the reagent in the reactor 20 in a non-contact eccentric oscillation manner.

S530, the sequence of actions or tasks performed by the mixing component 120 includes actions of moving into the reactor 20, adding a sample into the sample receiving pipetting unit 411, adding a reagent into the reagent receiving pipetting unit 310, eccentrically oscillating, moving out of the reactor 20 after mixing is completed, and the like, and a cyclically reproducible shortest time window is recorded as a first cycle, i.e. a minimum time interval between two consecutive times of performing the same action by the mixing component 120 is a first cycle. The value of the first period divided by the number of blend modules 120 is designated as the second period. From the time when the first mixing module 120 is moved into the reactor 20, and the time interval of the second period is staggered in sequence, and then the first mixing module 120 is moved into the reactor 20. It will be appreciated that to accomplish this, the duty cycle of the transport assembly 110 is the second cycle and the duty cycle of the blending assembly 120 is the first cycle. The transportation assembly 110 may synchronously drive the blending assembly 120 to cyclically reciprocate between the first station 11 and the second station 12 during each second cycle.

S540, the reactor 20 that has been mixed completely is shifted by a time interval of the second period in sequence, and then moved out of the mixing module 120, and a new reactor 20 is moved into the mixing module 120 that has been moved out of the reactor 20.

The invention can realize high-flux immunity test, the length of the second period can be any suitable value within 4-15 seconds, such as 4 seconds, 5 seconds, 6 seconds, 9 seconds and the like, and the corresponding test flux is 900-.

For convenience of description, 10 seconds will be described as an example.

Taking the example of the transportation assembly 110 driving the two blending assemblies 120 to move synchronously, if the immunoassay analyzer 10 must complete the measurement of one reactor 20 every 10 seconds, i.e., report a test result every 10 seconds, the second period is 10 seconds. Considering the whole immunoassay analyzer 10 as a flow line, it is necessary to ensure that the flow rates of all parts of the flow line are equal, so that the mixing device 100 also has to output a reactor 20 with the mixing processing completed every 10 seconds. If there is only one mixing assembly 120, since the total time required by the mixing assembly 120 in the sequence of operations of moving into the reactor 20, adding the sample by the sample pipetting unit 411, adding the reagent by the reagent pipetting unit 310, eccentrically shaking for mixing, and moving out of the reactor 20 that has been mixed completely in one cycle is greater than 10 seconds, the mixing apparatus 100 cannot output one reactor 20 that has been mixed completely every 10 seconds, and the flow rate of the mixing apparatus 100 is lower than the outlet flow rate of the flow line, so that the flow line cannot continuously operate at maximum efficiency. Therefore, by setting the first period to be twice the second period, that is, the first period is 20 seconds, and simultaneously setting the number of the kneading assemblies 120 to two, the sequence of actions performed by the two kneading assemblies 120 is performed with a time (that is, 10 seconds) that is staggered from the second period, that is, the two kneading assemblies 120 are "staggered in parallel" with each other by one second period, on the basis that each kneading assembly 120 outputs one reactor 20 that has been subjected to the kneading process every 20 seconds, the whole kneading apparatus 100 outputs one reactor 20 that has been subjected to the kneading process every 10 seconds, and finally, the purpose of "time conversion by number" is achieved.

Of course, an initial station 13 can be further provided, so that the transportation assembly 110 drives the blending assembly 120 to circularly reciprocate among the initial station 13, the first station 11 and the second station 12; at initial station 13, reactor 20 is moved into and out of blending assembly 120. The initial station 13, the first station 11 and the second station 12 can be arranged on the same straight line, and the initial station 13 is located between the first station 11 and the second station 12, so that the movement locus of the blending assembly 120 among the initial station 13, the first station 11 and the second station 12 is a straight line. The initial station 13, the first station 11 and the second station 12 may also be arranged on the same circumference, so that the blending assembly 120 performs a circular motion among the initial station 13, the first station 11 and the second station 12. Compared with the traditional blending assembly 120 which is fixed at a single station, the transportation assembly 110 drives the blending assembly 120 to circularly reciprocate among a plurality of stations, so that the blending assembly 120 can orderly complete different action sequences at different stations, the movement strokes of the sample pipetting unit 411, the reagent pipetting unit 310 and other units are reduced, more flexible and efficient task operation on the reactor 20 can be realized, such as tasks of receiving the reactor 20, receiving samples, reagents, blending and the like, and the test throughput of the whole machine is improved.

Specifically, when the tandem type kneading apparatus 101 starts to operate, a reactor 20 is first loaded on the first loading platform 1221 at the initial station 13, and at this time, no reactor 20 is loaded on the second loading platform 1222; the conveyor drives the first bearing platform 1221 and the second bearing platform 1222 to move from the initial station 13 to the first station 11, and samples are added into the reactor 20 on the first bearing platform 1221; the conveyor drives the first bearing platform 1221 and the second bearing platform 1222 to move from the first station 11 to the second station 12, and reagent is added into the reactor 20 containing the sample on the first bearing platform 1221; the first bearing platform 1221 generates eccentric oscillation, so that the sample and the reagent in the reactor 20 begin to be uniformly mixed; the conveyor drives the first bearing platform 1221 and the second bearing platform 1222 to return to the initial station 13 from the second station 12, at this time, the first bearing platform 1221 and the second bearing platform 1222 arrive at the initial station 13 in 10 seconds, and the reactor 20 is added to the second bearing platform 1221 for the first time; the conveyor drives the first and second carriers 1221, 1222 to move from the initial station 13 to the first station 11 again, adding the sample to the reactor 20 on the second carrier 1222; the conveyor drives the first bearing platform 1221 and the second bearing platform 1222 to move from the first station 11 to the second station 12 again, and reagent is added to the reactor 20 containing the sample on the second bearing platform 1222; the second bearing table 1222 generates eccentric oscillation to make the sample and the reagent in the reactor 20 begin to mix uniformly; the conveyor drives the first and second carriers 1221, 1222 to return from the second station 12 to the initial station 13, at which time the first and second carriers 1221, 1222 arrive at the initial station 13 at 20 seconds, add the reactor 20 a second time on the first carrier 1221, and move toward the first station 11. According to the mixing rule, when the first bearing platform 1221 and the second bearing platform 1222 arrive at the initial station 13 at the 20 th second time, the reactor 20 is loaded on the second bearing platform 1222 for the second time. By analogy, when the first carrying platform 1221 and the second carrying platform 1222 arrive at the initial station 13 at 20 th, 30 th, and 10 nth seconds (N ≧ 2), the reactor 20 is moved into the mixing apparatus 100. Similarly, since the duty cycle of each mixing module 120 is the first cycle (20 seconds) and the sequence of actions between the mixing modules 120 is staggered in parallel for the second cycle (10 seconds), each mixing module 120 completes one reactor 20 for mixing process every 20 seconds and moves out of the mixing device 100 to the reaction device 200, but the whole mixing device 100 outputs one reactor 20 for mixing process every 10 seconds, so that the flow rate of the mixing device 100 is equal to the outlet flow rate of the production line. In fact, when the reactor 20 on one of the mixing assemblies 120 is mixed, the mixing time is fully utilized, and the reactor 20 on the other mixing assembly 120 is added with the sample or reagent, so that the flow of the whole mixing device 100 meets the requirement of testing flux.

Of course, the first period may be longer while the second period is still 10 seconds, such that the number of the kneading assemblies 120 is three, four or more, and the first period may be three, four or more times the second period, i.e., the first period is 30 seconds or 40 seconds, etc. On the basis of ensuring the testing flux, the movement speed of the transportation assembly 110 can be reduced, the mixing time of the sample and the reagent is prolonged, and the bottleneck of the movement speed of the transportation assembly 110 and the bottleneck of the mixing time of the sample and the reagent are effectively solved. Under the condition that the moving speed of the transportation assembly 110 and the blending time of the sample and the reagent are fixed, each blending assembly 120 still outputs one reactor 20 with the blending completed every 20 seconds, that is, the first period is still 20 seconds, if the test throughput of the immunoassay analyzer 10 needs to be improved, for example, one measured reactor 20 is required to be output every 5 seconds (the second period), the number of blending assemblies 120 on the transportation assembly 110 can be increased to four; if it is desired to output a measured reactor 20 every 4 seconds (second cycle), the number of blending assemblies 120 on transport assembly 110 may be increased to five.

At least two blending positions can be arranged on each blending assembly 120, wherein the blending positions are accommodating holes 122a on the bearing platform 122, and when one blending position (accommodating hole 122a) is occupied by the reactor 20 which is blending or completes blending, the reactor 20 is moved to other idle blending positions (accommodating holes 122a) on the blending assembly 120. Therefore, the problem of occupation of the mixing position in the process of moving the reactor 20 in and out on the same bearing table 122 can be solved, and the testing efficiency and the testing flux are improved.

The blending process of the sample and the reagent in the reactor 20 can be performed after the transportation assembly 110 drives the blending assembly 120 to stop moving, or during the movement, for example, during the process of returning the blending assembly 120 from the second station 12 to the initial station 13, the driver 123 makes the bearing platform 122 eccentrically oscillate to blend the sample and the reagent. The time of the blending component 120 in the movement process can be fully utilized to blend the sample and the reagent by blending treatment in the movement process, so that the blending device 100 can meet the requirement of testing flux.

The time required from the beginning to the completion of the mixing in the reactor 20 loaded with the sample and the reagent is usually 2-10 seconds, the working period of the transportation assembly 110 is the first period, and the two mixing assemblies 120 are the second period, so that the sample and the reagent have enough time to be mixed, the sample and the reagent can be ensured to be fully reacted, and the accuracy of the subsequent measurement result is improved.

Referring to fig. 3 and fig. 4, in some embodiments, the blending device 100 is in parallel, the mixing device 102 in parallel includes at least two blending mechanisms 103, each blending mechanism 103 includes a transportation assembly 110 and a blending assembly 120, the blending assembly 120 is disposed on the transportation assembly 110, and the transportation assembly 110 drives the blending assembly 120 to move. For example, where each of the blending mechanisms 103 includes one transport assembly 110 and one blending assembly 120, the strokes of the individual blending assemblies 120 are in a parallel relationship to one another. The structure of the transportation assembly 110 and the blending assembly 120 is the same as the corresponding structure in the tandem blending device 100, that is, each transportation assembly 110 includes a frame 111 and a conveyor arranged on the frame 111, and each blending assembly 120 includes a support 121, a driver 123 and a bearing platform 122, which will not be described again. The main difference with the tandem type blending device 100 is that: the blending assemblies 120 are respectively arranged on different transportation assemblies 110, and the movement of the blending assemblies 120 on different transportation assemblies 110 is not synchronous.

In some embodiments, at least one of the blending mechanisms 103 includes a transportation component 110 and at least two blending components 120, the transportation component 110 drives the at least two blending components 120 to move synchronously, at this time, at least two blending components 120 of the blending mechanism 103 are connected in series, and the blending component 120 of the blending mechanism 103 is connected in parallel with the blending components 120 of other blending mechanisms 103, that is, the blending components 120 of the whole blending device 100 have parallel and serial (i.e., parallel-serial) relationships at the same time.

Referring to fig. 6, when the parallel type blending device 102 is used to blend the sample and the reagent, a parallel type blending method can be formed, and the parallel type blending method mainly includes the following steps:

s610, providing at least two transportation assemblies 110, and arranging a blending assembly 120 for carrying the reactor 20 on each transportation assembly 110, wherein each transportation assembly 110 drives the blending assembly 120 to circularly reciprocate between the first station 11 and the second station 12.

And S620, adding a sample into the reactor 20 at the first station 11, adding a reagent into the reactor 20 at the second station 12, and uniformly mixing the sample and the reagent in the reactor 20.

S630, the sequence of actions or tasks executed by the blending module 120 includes moving into the reactor 20, adding a sample into the sample receiving pipetting unit 411, adding a reagent into the reagent receiving pipetting unit 310, eccentrically oscillating, and moving out of the reactor 20 after blending is completed, and the shortest time window that can be cyclically reproduced is recorded as a first cycle, i.e., the minimum time interval between two consecutive times of executing the same action by the blending module 120 is the first cycle. The value of the first period divided by the number of blend modules 120 is designated as the second period. From the time when the mixing module 120 on one of the transporting modules 110 is first moved into the reactor 20, the mixing modules 120 on the other transporting modules 110 are sequentially moved into the reactor 20 by staggering the time interval of a second period. It will be appreciated that to accomplish the above steps, the duty cycle of each of the transport assembly 110 and the blending assembly 120 is the second cycle.

S640, sequentially moving the reactors 20 out of the mixing assembly 120 at intervals of a second period, and placing a new reactor 20 on the mixing assembly 120 moved out of the reactor 20.

The following description will be made by taking the example that the number of the transportation assemblies 110 is two, and one blending assembly 120 is provided on each transportation assembly 110, and please refer to the above description for the same point with the tandem blending method. Assuming that the second period is 10 seconds, and each blending mechanism 103 outputs one blended reactor 20 every 20 seconds, that is, the first period is 20 seconds, since the time (10 seconds) between two periods is staggered in sequence and the reactors 20 are moved into the blending assemblies 120 on the other transport assemblies 110, finally the whole blending device 100 outputs one blended reactor 20 every 10 seconds, which can also play a role of "time conversion".

Referring to the above description of the serial blending method, in the parallel blending method, the initial station 13 may also be provided, so that the transportation component 110 drives the blending component 120 to circularly reciprocate among the initial station 13, the first station 11 and the second station 12; at initial station 13, reactor 20 is moved into and out of blending assembly 120. The initial station 13, the first station 11 and the second station 12 can be arranged on the same straight line, and the initial station 13 is located between the first station 11 and the second station 12, so that the movement locus of the blending assembly 120 among the initial station 13, the first station 11 and the second station 12 is a straight line.

Compared with the traditional blending assembly 120 which is fixed at a single station, the transportation assembly 110 drives the blending assembly 120 to do reciprocating motion circularly among a plurality of stations, so that the testing flux of the whole machine is improved.

Each blending assembly 120 is provided with at least two blending positions, the blending positions are the containing holes 122a on the bearing platform 122, and the two blending positions are used simultaneously or alternately, so that the treatment efficiency of the blending assemblies 120 on the reactor 20 can be improved. When one of the mixing stations (receiving hole 122a) is occupied, the reactor 20 can be moved to another mixing station (receiving hole 122a) on the mixing assembly 120. The sample and the reagent in the reactor 20 can be mixed during the process that the transportation component 110 drives the mixing component 120 to move or after the movement is stopped, that is, the mixing of the sample and the reagent in the reactor 20 is not limited by the movement state of the transportation component 110, so that the mixing device 100 is more flexible and efficient.

Specifically, when the parallel kneading apparatus 100 starts operating, one of the transport units 110 is referred to as a first transport unit 1101, and the other transport unit 110 is referred to as a second transport unit 1102. A reactor 20 is added to the carrier 122 on the first transport assembly 1101 at the initial station 13 for the first time, while no reactor 20 is added to the carrier 122 on the second transport assembly 1102.

For the first transport assembly 1101, adding a sample to the reactor 20 on the carrier table 122 of the first transport assembly 1101 as it moves from the initial station 13 to the first station 11; the first transportation assembly 1101 moves from the first station 11 to the second station 12, and reagent is added into the reactor 20 containing the sample on the bearing platform 122 of the first transportation assembly 1101; the platform 122 of the first transport assembly 1101 eccentrically oscillates to mix the sample and the reagent in the reactor 20.

For the second transport assembly 1102, the reactor 20 is first added to the susceptor 122 on the second transport assembly 1102 at 10 seconds after the reactor 20 is first added to the susceptor 122 on the first transport assembly 1101, and the second transport assembly 1102 is caused to start moving according to the movement law of the first transport assembly 1101. By analogy, when the carrier 122 on the first transportation assembly 1102 and the carrier 122 on the second transportation assembly 1102 reach the initial station 13 at 20 th, 30 th and 10 nth seconds, the reactor 20 moves into the mixing device 100. Similarly, since the duty cycle of each mixing module 120 is the first cycle (20 seconds) and the sequence of the operations between the mixing modules 120 is staggered in parallel for the second cycle (10 seconds), each mixing module 120 completes one mixing-processed reactor 20 every 20 seconds and moves out of the mixing apparatus 100 to the reaction apparatus 200, but the whole mixing apparatus 100 outputs one mixing-processed reactor 20 every 10 seconds.

For the parallel mixing method, the transportation assembly 110 drives the mixing assembly 120 to separate from each other by a second period (10 seconds) and to "stagger parallel", although each mixing mechanism 103 outputs a mixed reactor 20 by 20 seconds (first period), the two mixing mechanisms 103 stagger by 10 seconds and start to operate from the initial station 13, so that the whole mixing device 100 outputs a mixed reactor 20 by every 10 seconds (second period). By increasing the number of the blending mechanisms 103, the transportation assembly 110 can move at a slower speed on the basis that the flow of the whole blending device 100 meets the requirement of testing flux, so that the bottleneck of the movement speed of the transportation assembly 110 and the bottleneck of the blending time between samples and reagents are solved. For other similarities, refer to the above description of the tandem blending method.

When the number of the blending assemblies 120 arranged on at least one of the transportation assemblies 110 is not less than two, the transportation assembly 110 drives all the blending assemblies 120 arranged thereon to move synchronously, that is, at least one blending mechanism 103 comprises at least two blending assemblies 120, and the blending assemblies 120 on the blending mechanism 103 are in a serial relationship, so that the blending assemblies 120 on the whole blending device 100 have a parallel and serial relationship at the same time, similarly, each blending assembly 120 is added into the reactor 20 for the first time at a time interval of a second period, and finally, the whole blending device 100 outputs one reactor 20 which is blended and processed at a time interval of the second period. By placing some of the blending assemblies 120 in series, the overall blending apparatus 100 can be made more compact.

Referring to fig. 1 and 3, in some embodiments, the reagent supplying apparatus 300 is disposed near the second station 12, the reagent supplying apparatus 300 includes a reagent pipetting unit 310 and a storage unit 320, the number of the storage units 320 is at least two, a plurality of storage parts 321 are disposed on the storage unit 320, the storage parts 321 are used for placing and storing reagent containers, reagents are contained in the reagent containers, and the reagent pipetting unit 310 is used for sucking reagent components in the reagent containers on the storage parts 321 and adding the reagent components to the reactor 20 at the second station 12. The number of the storage parts 321 can be set as required, and considering the use requirement, cost and layout, the number of the storage parts 321 on each storage unit 320 is preferably 15-50, for example, the number of the storage parts 321 on each storage unit 320 is 25, so that a total of 50 reagent containers can be simultaneously stored on line in two storage units 320. Each storage unit 320 stores all reagent components required for a corresponding analysis item, for example, in one analysis item, three reagent components of magnetic particles, enzyme label and dissociation agent must be added to the reactor 20, and the three components of magnetic particles, enzyme label and dissociation agent are contained in the same storage unit 320. When a particular analysis project requires multiple reagent containers to be loaded to expand the on-board test volume of the project, the multiple reagent containers may be stored in any suitable combination in each storage unit. For example, when the number of the storage units is 2, 3 TSH (thyroid stimulating hormone) reagent containers each containing 100 TSH to be tested need to be loaded, all of the 3 TSH reagent containers may be loaded in the same storage unit, or 1 TSH reagent container may be loaded in one storage unit, and the other 2 TSH reagent containers may be loaded in the other storage unit.

With the conventional reagent supplying device 300, in order to increase the storage capacity of the analysis items, the number of the storage parts 321 must be increased, which results in an increase in the size of the whole storage unit 320, and the storage unit 320 occupies a large area, which is not favorable for the layout and production of the storage unit 320, and on the other hand, with the storage unit 320 having a large volume and weight, the difficulty of controlling the movement thereof is also increased, so that the storage parts 321 cannot reach the designated position in a short time for the reagent pipetting unit 310 to aspirate the reagent, which is a bottleneck in achieving a high test throughput. In addition, the conventional reagent supplying apparatus 300 stores a plurality of reagent components for the same analysis item in different storage units 320, so that the reagent pipetting unit 310 pipettes the reagent for the same analysis item on the different storage units 320, which results in a large stroke and complex motion logic of the reagent pipetting unit 310, and thus high test throughput cannot be realized, and further requires the reagent components to be stored in a plurality of reagent containers, which results in problems of high production and manufacturing costs, inconvenience for user operation, and the like.

The reagent supply device 300 of the above embodiment is provided with at least two storage units 320, and each storage unit 320 has a small volume, thereby being beneficial to overall layout and motion control, and also ensuring that the whole reagent supply device 300 has a large reagent storage capacity. Meanwhile, each storage unit 320 stores all reagent components required by a corresponding analysis item, so that the reliability and fault tolerance of the reagent supply device 300 can be improved, and when one storage unit 320 fails to work, the other remaining storage units 320 can continue to work, so that the reagent supply device 300 can still work effectively. Of course, a failed memory cell 320 may be refurbished while other memory cells 320 are operating.

The storage unit 320 may be a rotary disk which periodically and intermittently rotates to bring the storage portion 321 to a designated position (i.e., the pipetting station 14), so that the reagent pipetting unit 310 pipettes the reagent on the storage portion 321 at the pipetting station 14. The reagent pipetting units 310 may be equal in number to the number of rotating discs, one for each reagent pipetting unit 310, each reagent pipetting unit 310 aspirating reagent from its corresponding rotating disc. Similar to the sample pipetting unit 411, the reagent pipetting unit 310 may be a steel needle or a disposable nozzle, and in order to achieve smooth reagent pipetting, the reagent pipetting unit 310 may perform vertical up-and-down movement, horizontal linear movement or horizontal rotation and other movement forms. Of course, the number of reagent pipetting units 310 can also be one, the one reagent pipetting unit 310 pipetting reagent in a plurality of rotating discs.

The reagent supplying apparatus 300 further includes a scanner provided on the storage unit 320, and the scanner can recognize barcode information of the reagent container on the storage part 321, thereby distinguishing different reagents. In order to make the entire reagent supplying apparatus 300 compact, the scanner is fixedly installed. The storage unit 320 may further be provided with a refrigerator, and the refrigerator may perform a refrigeration process on the reagent in the storage part 321, thereby implementing an online long-term preservation of the reagent.

Referring to fig. 7, in order to realize a high-throughput immunoassay, when the reagent is aspirated by using the above-described reagent supplying apparatus 300, an aspiration method of the reagent may be formed, the aspiration method mainly including the steps of:

s710, the reagent pipetting unit 310 and at least two storage units 320 for storing reagents are provided, and reagent containers are stored in the plurality of storage sections 321 of the storage unit 320, so that each storage unit 320 stores all reagent components necessary for a corresponding analysis item.

S720, the storage part 321 is moved along with the storage unit 320, and the reagent pipetting unit 310 pipettes the reagent from the storage part 321 that arrives at the pipetting station 14. The movement of the storage unit 320 may be a rotation, for example, the storage unit 320 is periodically rotated intermittently, so that the storage portion 321 arrives at the pipetting station 14 at every set time, so that the reagent pipetting unit 310 pipettes the reagent.

S730, the shortest time window in which the motion sequence executed by each storage unit 320 can recur circularly is recorded as a first period, i.e. the minimum time interval between two consecutive executions of the same motion by the storage unit 320 is the first period. The value obtained by dividing the first period by the number of memory cells 320 is denoted as a second period. When one of the storage units 320 first drives the storage portion 321 to move toward the pipetting station 14, the time interval of a second period is staggered in sequence, so that the other storage units 320 drive the storage portion 321 to move toward the corresponding pipetting station 14.

Taking two storage units 320 as an example, the value of the second period is equal to the value of the second period mentioned in the above-mentioned mixing method according to the principle that the flow rate is equal everywhere, and taking 10 seconds as an example, that is, one storage part 321 arrives at the pipetting station 14 every 10 seconds for the reagent pipetting unit 310 to aspirate the reagent. Of course, the value of the first period is the same as the value of the first period mentioned in the above-mentioned method of homogenisation, i.e. the value of the first period is 20 seconds. Referring to the basic principle of the blending method, two storage units 320 are separated by a second period and are staggered in parallel, although each storage unit 320 has a storage part 321 reaching the corresponding pipetting station 14 every 20 seconds, the action sequences of the two storage units 320 are staggered by 10 seconds and are started to be executed, so that the whole reagent supply device 300 has a storage part 321 reaching the pipetting station 14 every 10 seconds for the reagent pipetting unit 310 to aspirate the reagent, and by increasing the number of the storage units 320 for the time of pipetting, on the basis that the flow of the whole reagent supply device 300 meets the requirement of the test throughput, the storage units 320 can rotate at a slower speed, and then the bottleneck of the movement speed of the storage units is solved. Of course, when the number of the storage units 320 is larger, the flow rate of the entire reagent supplying apparatus 300 can be increased without changing the rotation speed of the storage units 320, thereby improving the test throughput of the immunoassay analyzer 10.

In some embodiments, if the immunoassay test throughput is reduced or the movement speed of the storage unit is increased by other costly designs, and the movement speed of the storage unit 320 does not become a bottleneck in the immunoassay test throughput, the sequence of motions of the plurality of storage units 320 can be "synchronized serial," i.e., the sequence of motions of the plurality of storage units 320 are synchronized during a work cycle, and in serial between work cycles, each storage unit 320 can position the target storage 321 to the pipetting station 14 for reagent pipetting unit 310 to aspirate reagent during each work cycle, but only one storage unit 320 is required to position the target storage 321 to the pipetting station 14 for reagent pipetting unit 310 per work cycle. Two memory cells 320 (respectively referred to as a first memory cell and a second memory cell) and a duty cycle of 10 seconds are taken as an example for explanation. At the 1 st 10 seconds, one storage portion 321 of the first storage unit arrives at the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; for the 2 nd 10 seconds, one storage portion 321 of the second storage unit arrives at the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; for the 3 rd 10 seconds, one storage portion 321 of the first storage unit arrives at the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; in this manner, two storage units 320 are alternately connected in series every 10 seconds, and one storage portion 321 is brought to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent. Of course, the first storage unit may position the storage section 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent for the nth 10 seconds (N ≧ 1) of 1 st, 2 nd, and … th; the nth (N +1) th (N + M) th (M ≧ 1) … th (N + M), the second storage unit positions the storage section 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate a reagent. In any case, in any working cycle, one of the storage units can position the storage part 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent.

All reagent components required for testing the corresponding analysis items are stored in the same storage unit 320, so that the reagent pipetting unit 310 can conveniently and rapidly aspirate the reagent, and the flow rate of the reagent supplied by the reagent supply device 300 can be increased. On the other hand, when the storage unit 320 fails, the instrument can continue testing by using other storage units 320, normal operation of instrument testing is not affected, and fault tolerance is improved. In addition, all reagent components required by one test corresponding to an analysis project are placed in the same storage unit 320, and can be contained in one reagent container with a plurality of reagent cavities, so that the production and manufacturing cost is saved, and the operations of loading and unloading and the like of a user are facilitated.

During the rotation (revolution) of the storage part 321 along with the storage unit 320, at least one chamber of the reagent container on the storage part 321 (such as a magnetic particle chamber for containing magnetic particle reagent components) is made to rotate around its own central axis, so that the magnetic particle reagent components existing in the form of solid suspension are made to swirl, and the solid matters (such as magnetic particles) therein are prevented from being precipitated.

The plurality of storage units 320 are independently arranged, that is, each storage unit 320 can independently rotate to position the reagent on the storage portion 321 to the pipetting station 14. It should be noted that the "independent setting" herein is not related to the spatial layout and physical location between the storage units 320, for example, a plurality of storage units 320 may be distributed on the instrument without overlapping, and one storage unit 320 may be nested on the periphery or inside of another storage unit 320. Of course, for better layout and control, the plurality of memory cells 320 are preferably identically constructed and separately arranged. The plurality of storage units 320 are independently arranged, so that the flexibility of control can be improved, the efficiency of reagent supply can be further improved, and the processing flux of the instrument can be improved.

It is possible to have equal numbers of reagent pipetting units 310 and storage units 320, with one reagent pipetting unit 310 for each storage unit 320, i.e. each storage unit 320 is aspirated by its corresponding reagent pipetting unit 310. Obviously, when the number of the reagent pipetting units 310 is increased, the running speed of each reagent pipetting unit 310 can be reduced on the basis of meeting the test throughput, and the bottleneck of the moving speed of the reagent pipetting units 310 is solved.

Referring to fig. 1 and 3, in some embodiments, the reaction apparatus 200 includes a rotating plate 210, a transferring assembly 220, a measuring unit 230, and a cleaning assembly 250. The rotating disc 210 is provided with an incubation ring 203, a cleaning ring 202 and a measurement ring 201, the incubation ring 203, the cleaning ring 202 and the measurement ring 201 are all arranged around the rotating center of the rotating disc 210, the incubation ring 203 is provided with incubation positions 213, and the incubation positions 213 are arranged at intervals along the circumferential direction of the incubation ring 203; the cleaning ring 202 is provided with cleaning positions 212, and the cleaning positions 212 are arranged at intervals along the circumferential direction of the cleaning ring 202; the measuring ring 201 is provided with measuring positions 211, and the measuring positions 211 are arranged at intervals along the circumferential direction of the measuring ring 201. The incubation position 213, the cleaning position 212 and the measurement position 211 are used for placing the reactor 20, and the three positions can be slots or brackets and other structures suitable for carrying the reactor 20. The measuring unit 230 is connected to the rotating disc 210, and the measuring unit 230 can measure the optical signal of the reaction vessel 20 after the signal reagent is added, so as to further analyze the reactant. The cleaning assembly 250 is located above the cleaning ring 202 and includes a liquid injection part for injecting a cleaning buffer solution into the reactor 20 at the cleaning position 212 and a liquid absorption part which can be lowered and raised into and out of the reactor 20 at the cleaning position 212 to extract and remove unbound components in the reactor 20. Further, for the sake of a simplified structure, the cleaning assembly 250 further includes a signal reagent injection part for injecting a signal reagent into the reactor 20 after the cleaning separation at the cleaning station 212. In some embodiments, the reaction apparatus 200 further comprises a waste liquid absorbing assembly 240 and a signal reagent blending unit 430. Inhale waste liquid subassembly 240 and be located the top of measuring ring 201, after reactor 20 measures, inhale waste liquid subassembly 240 can descend and rise and pass in and out the reactor 20 on measuring position 211, with the waste liquid (mainly being signal reagent) absorption in the reactor 20, move the reactor 20 after removing the waste liquid to abandoning the station at last to realize the branch of solid rubbish and liquid rubbish and put the processing, reduce the biohazard risk. Further, the waste liquid absorbing assembly 240 can be connected to the liquid absorbing part of the cleaning assembly 250, and together with the liquid absorbing part of the cleaning assembly 250, can be lowered to the bottom in the reactor to absorb liquid, and then lifted away from the reactor after absorption. Therefore, the function of the cleaning component 250 can be fully utilized, the mechanism volume is reduced, the cost is saved, and the problems of complex structure, high cost and the like caused by independently arranging a waste liquid sucking component are solved. The signal reagent blending unit 430 is disposed independently of the rotating disk 210, and includes a blending assembly similar to or the same as the blending assembly 120, and performs eccentric oscillation blending on the reactor 20 containing the signal reagent.

The transferring component 220 moves the reactor 20 after the mixing process from the mixing device 100 to the incubation position 213, and the incubation position 213 incubates the sample and the reagent after the mixing process in the reactor 20 for a set time while the reactor 20 rotates along with the rotating disc 210. After the reactor 20 is incubated, the transfer module 220 transfers the reactor 20 from the incubation position 213 to the cleaning position 212, in the process that the reactor 20 rotates along with the rotating disc 210, the liquid injection part of the cleaning module 250 can inject cleaning liquid into the reactor 20 in the cleaning position 212, then the magnetic particle compound is adsorbed on the inner side wall of the reactor 20 through a magnetic field, the liquid absorption part of the cleaning module 250 extracts unbound components from the reactor 20, and after multiple rounds of 'injection of cleaning liquid, adsorption and extraction of unbound components', reactants of the reactor 20 are cleaned and separated. After the washing and separation of the reactant in the reactor 20 are completed, the signal reagent injection unit may add the signal reagent to the reactor 20, and the transfer unit 220 may transfer the reactor 20 to which the signal reagent is added from the washing station 212 to the signal reagent kneading unit 430, and may knead the signal reagent by the signal reagent kneading unit 430. In order to ensure that the signal reagent is fully mixed without influencing the testing flux of the instrument, the mixing time of the signal reagent is 2-6 seconds. After the mixing of the reactor 20 containing the signal reagent is completed, the transferring assembly 220 transfers the reactor 20 from the signal reagent mixing unit 430 to the measuring position 211, if signal incubation needs to be continued for the reactor 20 containing the signal reagent, the measuring position 211 incubates the reactor 20 for a set time while the reactor 20 rotates along with the rotating disc 210, and when the reactor 20 moves forward along with the rotating disc 210 to the position of the measuring device 230, the measuring device 230 measures the signal of the reactant in the reactor 20 so as to analyze the reactant.

The incubation ring 203, the cleaning ring 202 and the measurement ring 201 are concentrically arranged, that is, the three are all centered on the rotation center of the rotating disk 210. The incubation ring 203, the cleaning ring 202 and the measurement ring 201 are arranged at intervals from inside to outside in sequence around the rotation center, namely the measurement ring 201 is close to the edge of the rotating disc 210, the incubation ring 203 is close to the center of the rotating disc 210, and the cleaning ring 202 is arranged between the incubation ring 203 and the measurement ring 201. In order to meet the requirement of the incubation time of the analysis item, while ensuring the number of the incubation positions 213, the rotating disc 210 of the reaction device 200 is not oversized, the number of the incubation circles 203 is at least two, and for example, may be 2 to 10, wherein the incubation circle 203 closest to the rotation center is referred to as an inner incubation circle, and the incubation circle 203 farthest from the rotation center is referred to as an outer incubation circle. The number of the cleaning rings 202 is set to 1-2 as required for cleaning efficiency. The number of the measuring rings 201 is 1, which can meet the measuring requirement.

The reaction apparatus 200 is provided with an incubation in-and-out station 15, a wash in-and-out station 16, a wash out-and-out station 17, and a measurement in-and-out station 18. In order that the reactor can enter and exit each incubation ring 203, cleaning ring 202 and measuring ring 201 of the reaction device 200, the number of the incubation in-out stations 15 is not less than the number of the incubation rings 203, the number of the cleaning in-out stations 16 and the number of the cleaning out-out stations 17 are respectively equal to the number of the cleaning rings 202, and the number of the measuring in-out stations 18 is not less than the number of the measuring rings 201, namely at least one. Further, in order to make the layout of the whole machine compact, reduce the movement stroke of the transfer assembly 220, improve the reliability of the transfer assembly, and further improve the working efficiency, the cleaning moving-in station 16 and the cleaning moving-out station 17 are respectively arranged at two sides of the rotation center of the rotating disc 210, namely at two ends of the diameter of the cleaning ring 202, the incubation in-out station 15 is at the same side as the cleaning moving-in station 16, and the measurement in-out station 18 is at the same side as the cleaning moving-out station 17. The reactor thus removed from the incubation and in-and-out station 15 can be moved proximally from the wash transfer station 16 to the wash ring 202, and the reactor removed from the wash transfer station 17 can be moved proximally from the measurement and in-and-out station 18 to the measurement ring 201.

Specifically, taking the test of the one-step reaction mode as an example, the transfer module 220 moves the reactor 20 on the mixing device 100 from the incubation entry and exit station 15 to the incubation position 213, and when the reactor 20 moves to the incubation entry and exit station 15 following the rotating disc 210, the transfer module 220 moves the reactor 20 from the incubation entry and exit station 15 to the incubation position 213 and from the cleaning entry station 16 to the cleaning position 212; when the reactor 20 moves to the cleaning removal station 17 along with the rotating disc 210, the transfer assembly 220 moves the reactor 20 out of the cleaning location 212 from the cleaning removal station 17 and into the signal reagent blending unit 430 for signal reagent blending, and after the signal reagent blending is completed, the reactor 20 moves into the measurement location 211 from the measurement in-and-out station 18; when the reactor 20 moves to the position of the measurer 230 along with the rotating disc 210, after the measurer 230 finishes measuring the reaction signal, the reactor 20 continues to move to the position of the waste liquid suction assembly 240 along with the rotating disc 210, the waste liquid suction assembly 240 sucks all waste liquid in the reactor 20, the reactor 20 after sucking the waste liquid continues to move to the measurement in-out station 18 along with the rotating disc 210, and at this time, the transfer assembly 220 moves the reactor 20 after completing the measurement and sucking the waste liquid out of the measurement position 211 and moves the reactor 20 into a discarding station at the measurement in-out station 18. When performing other reaction mode tests, such as the delayed one-step or two-step test, transfer module 220 can move reactor 20 removed from incubation access station 15 at incubation location 213, and reactor 20 removed from wash removal station 17 at wash location 212 into blending apparatus 100.

The movement locus of the transfer unit 220 between the initial station 13, the incubation in-out station 15, the wash in-out station 16, the wash out station 17 and the measurement in-out station 18 is a straight line passing through the rotation center of the rotating disk 210 in the orthographic projection of the rotating disk 210. Therefore, the movement of the transfer assembly 220 can be simplified, and the working efficiency of the transfer assembly 220 can be improved so as to meet the requirement of testing flux. The straight line of the motion trail of the transfer assembly 220 also passes through the signal reagent blending unit 430, and the transfer assembly 220 can transfer the reactor 20 between the signal reagent blending unit 430, the measuring ring 201 and the cleaning ring 202.

To reduce the movement stroke of the single transfer unit 220 and further improve the work efficiency and control accuracy, the number of transfer units 220 may be set to two, and the relay station 214 may be provided within the inner incubation circle (closest to the rotation center) of the rotating disk 210, the relay station 214 being used to temporarily carry the reactor 20. The motion track of one transfer assembly 220 forms a first projection on the rotating disc 210, the motion track of the other transfer assembly 220 forms a second projection on the rotating disc 210, and the first projection and the second projection are connected to form a same straight line at the relay station 214 and are recorded as a track straight line; a line passing through the relay station 214 and perpendicular to the trajectory line is taken as a reference line. One of the transfer units 220 is responsible for the transfer of the portion of the reactor 20 located to the right of the reference line, and the other transfer unit 220 is responsible for the transfer of the portion of the reactor 20 located to the left of the reference line. For example, in the two-step reaction mode test, when the transfer unit 220 moves the reactor 20 from the cleaning removal station 17 to the cleaning position 212 and moves the reactor 20 to the mixing unit 120 for filling with the second reagent, it is necessary to transfer the reactor 20 from the left part to the right part of the reference line, the reactor 20 may be transferred from the cleaning position 212 of the left part of the reference line to the relay station by one transfer unit 220, and then the reactor 20 may be transferred from the relay station to the mixing unit 120 of the right part of the reference line by another transfer unit 220.

In some embodiments, the relay station 214 is disposed at the center of rotation of the carousel 210 for compact layout and to further improve the efficiency of the coordination between the transfer assemblies 220, and thus the instrument throughput.

Referring to fig. 1 and 3, in the immunoassay analyzer 10, the transportation assembly 110, the homogenizing assembly 120, the sample pipetting unit 411 and the reagent pipetting unit 310 can be combined to form a dilution apparatus, that is, the dilution apparatus includes the transportation assembly 110, the homogenizing assembly 120 and the pipetting assembly, and the pipetting assembly includes the sample pipetting unit 411 and the reagent pipetting unit 310, of course, the structures and positions of the transportation assembly 110, the homogenizing assembly 120, the sample pipetting unit 411 and the reagent pipetting unit 310 can be kept unchanged. Similarly to the blending apparatus 100, the diluting apparatus may also be provided with an initial station 13, a first station 11 and a second station 12, and of course, the initial station 13 may be omitted.

The blending assembly 120 is disposed on the transporting assembly 110, and the blending assembly 120 can simultaneously carry at least two reactors 20, for example, two reactors 20, wherein one reactor 20 is referred to as a first reactor and the other reactor 20 is referred to as a second reactor. The blending component 120 is provided with at least two containing holes 122a, and the first reactor and the second reactor can be respectively placed in different containing holes 122 a. The transport assembly 110 drives the blending assembly 120 between the initial station 13, the first station 11, and the second station 12.

During operation of the dilution apparatus, the first reactor is transferred from the supply tray into the trim assembly 120 by the transfer assembly 220 while the trim assembly 120 is at the initial station 13; when the blending assembly 120 moves to the first station 11, the sample is sucked by the sample pipetting unit 411 and added into the first reactor; when the blending assembly 120 moves to the second station 12, the diluent is sucked by the reagent pipetting unit 310 and added into the first reactor, and the sample and the diluent are blended to form a diluted sample; when the blending assembly 120 returns to the initial station 13 again, the blending assembly 120 is moved into the second reactor through the transfer assembly 220; when the blending assembly 120 moves to the first station 11 again, a part of the diluted sample is transferred from the first reactor to the second reactor through the sample pipetting unit 411, and when the blending assembly 120 moves to the second station 12 again, the reagent pipetting unit 310 sucks the reagent components to be added into the second reactor containing the diluted sample, and the diluted sample and the reagent components are blended; when the mixing module 120 is finally moved to the initial station 13, the second reactor is moved into the incubation position 213 of the reaction apparatus 200 by the transfer module 220. Of course, the first reactor may be moved to a discard station for disposal. According to the above operation rule, the diluting device can continuously output the reactor 20 in which the diluted sample and the reagent component are uniformly mixed, thereby realizing the automatic dilution of the sample.

Further, in order to improve the efficiency of automatic dilution of the sample, the number of the mixing assemblies 120 is at least two, each mixing assembly 120 can realize automatic dilution of the sample, and the mixing assemblies 120 can realize automatic dilution of the sample in parallel or in series. Similar to the aforesaid tandem type blending device, the same transportation component 110 synchronously drives the blending component 120 to circularly reciprocate between the first station 11 and the second station 12; similar to the parallel type blending device, at least two transport assemblies 110 are provided, each transport assembly 110 is provided with a blending assembly 120 for carrying the reactor 20, and each transport assembly 110 drives the blending assembly 120 to circularly reciprocate between the first station 11 and the second station 12.

Referring to fig. 8, when the dilution apparatus is used to automatically dilute the sample and mix the diluted sample and the reagent components, a dilution method may be formed, which mainly includes the following steps:

s810, carrying the first reactor by the blending component 120, moving the first reactor to a first station 11, and adding a sample into the first reactor 20;

s820, moving the first reactor containing the sample to the second station 12, and adding diluent into the first reactor;

s830, uniformly mixing the sample in the first reactor with the diluent to form a diluted sample;

s840, moving a second reactor to the blending component 120, moving the second reactor to the first station 11 again, and adding a part of the diluted sample in the first reactor 20 to the second reactor;

s850, moving the blending assembly 120 to the second station 12, and adding reagent components into the second reactor; and

and S860, uniformly mixing the diluted sample and the reagent component in the second reactor, and transferring the second reactor to the incubation position 213 of the reaction device 200 after the diluted sample and the reagent component are uniformly mixed.

When the number of the homogenizing assemblies 120 is at least two, each of the homogenizing assemblies 120 can be used alternately in the dilution step described above. Taking two blending components 120 as an example, the first blending component is used for automatically diluting the first sample, the second blending component is used for diluting the second sample, and the first blending component … is used for automatically diluting the third sample

To improve the efficiency of operation, both the diluent and reagent components are placed on the same storage unit 320. After a part of the diluted sample is added to the second reactor, the first reactor is moved out of the blending assembly 120 and discarded to the discarding station, and of course, in order to realize solid-liquid separation, the rest diluted sample in the first reactor may be first sucked, and then the first reactor formed after the diluted sample is completely sucked is discarded.

To facilitate movement of the reactors 20 into and out of the blending assembly 120, the blending assembly 120 is cyclically reciprocated between an initial station 13, a first station 11 and a second station 12, the first and second reactors 20 being moved into and out of the blending assembly 120 at the initial station 13. Similarly, the initial station 13, the first station 11 and the second station 12 are arranged in the same line, so that the initial station 13 is located between the first station 11 and the second station 12. The mixing component 120 mixes the sample and the diluent in the first reactor 20 and the diluted sample and the reagent in the second reactor 20 by non-contact eccentric oscillation.

It can be seen that the dilution device of the present invention integrates the blending assembly 120, and can move between different stations to complete automatic dilution and blending of samples, thereby avoiding the dilution of the pipetting unit at a fixed station and then the blending of the samples by transferring the reactor to another station, improving the efficiency and effect of dilution and blending, and solving the problem of high-throughput bottleneck of immunoassay test limited by automatic dilution of samples.

Referring to fig. 9, an immunoassay method, for example, a one-step reaction mode of immunoassay, can be formed by using the above-mentioned immunoassay analyzer 10, and the immunoassay method mainly includes the following steps:

s910, providing at least two blending assemblies 120 for carrying the reactor 20, and enabling the blending assemblies 120 to drive the reactor 20 to reciprocate between the first station 11 and the second station 12.

S920, the shortest time window in which the action sequence or the task executed by the blending module 120 can recur circularly is recorded as a first period, that is, the minimum time interval between two consecutive times of executing the same action by the blending module 120 is a first period, and a value obtained by dividing the first period by the number of the blending modules 120 is recorded as a second period. From the time when the first mixing module 120 is moved into the reactor 20, and the time interval of the second period is staggered in sequence, and then the first mixing module 120 is moved into the reactor 20.

S930, sequentially moving the reactor 20 out of the mixing module 120 at intervals of a second period, and moving the reactor 20 to a new reactor 20 on the mixing module 120 moved out of the reactor 20.

And S940, the reactor 20 which is moved out of the blending component 120 and contains the reactants is sequentially incubated, cleaned, separated and measured. The incubation time of the reactor 20 is between 5 and 60 minutes.

It is understood that the second period is equal to the time between the consecutive output of two adjacent measured reactors 20 from the reaction apparatus 200, i.e., the time between the consecutive reporting of two adjacent test results by the immunoassay analyzer 10.

When performing the reaction mode test of other methods, such as the delayed one-step method and the two-step method, in step S940, the incubated or washed reactor 20 may be moved into the mixing apparatus 100 again according to steps S920 and S930 to add the second reagent and mix, and after mixing, incubation, washing separation and measurement may be performed according to step S940.

Specifically, the incubation of step S940 may further include a first incubation and a second incubation as follows:

a first incubation, in which the reactor 20 containing the sample and the first reagent is incubated for a set time.

And a second incubation step of adding a second reagent to the reactor 20 after the first incubation step and then incubating for a set time.

When the incubation includes the first incubation and the second incubation, before the washing step, the reactor 20 after the first incubation is moved into the mixing apparatus 100 again according to the steps S920 and S930 to add the second reagent and mix, and after the mixing is completed, the second incubation, the washing separation and the measurement are performed according to the step S940.

The reagent is added into the reactor 20 twice, and the reagent components are added each time and then uniformly mixed in the reactor 20 through the uniformly mixing device 100. In some embodiments, the immunoassay method further comprises the steps of:

performing a first washing on the reactor 20 after the first incubation;

performing a second incubation on the reactor 20 subjected to the first cleaning treatment;

the reactor 20 subjected to the second incubation is subjected to a second washing.

Specifically, after the reactor 20 passes through steps S910, S920, and S930, first incubating the reactor 20 with the reaction device 200, then washing the reactor 20 after the first incubation with the reaction device 200 for the first time, after the first washing, moving the reactor 20 into the mixing device 100 again according to steps S920 and S930 to add the second reagent and mix the reagent uniformly, and after the mixing is completed, incubating, washing and measuring the second time according to step S940.

In some embodiments, for example, the same transport assembly 110 drives all of the blending assemblies 120 to move synchronously, i.e., the sample and reagents in the reactor 20 are blended using the above-described in-line blending method. In another example, the number of the transportation assemblies 110 is multiple, and each transportation assembly 110 drives at least one of the blending assemblies 120 to move, i.e. the sample and the reagent in the reactor 20 are blended by the above-mentioned parallel blending method.

Referring to the above-mentioned serial and parallel blending methods, the transportation component 110 can drive the blending component 120 to reciprocate cyclically among the initial station 13, the first station 11 and the second station 12; at initial station 13, reactor 20 is moved into and out of blending assembly 120, a sample is added to reactor 20 at first station 11, and reagents are added to reactor 20 at second station 12.

Referring to the structure and the working principle of the reaction apparatus 200, the reactor 20 may enter the incubation position 213 on the rotating disc 210 from the incubation in-out station 15 for incubation, the reactor 20 enters the washing position 212 on the rotating disc 210 from the washing moving-in station 16 for washing and separation, the reactor 20 moves the reactor 20 after washing and separation out of the washing position 212 from the washing moving-out station 17, and the reactor 20 moves into the measurement position 211 on the rotating disc 210 from the measurement in-out station 18 for measurement; the movement locus of the transfer unit 220 between the incubation entry and exit station 15, the wash entry station 16, the wash exit station 17 and the measurement entry and exit station 18 is aligned.

A relay station 214 is arranged in the inner incubation circle of the rotating disc 210 (closest to the rotation center), in particular, the relay station 214 for temporarily carrying the reactor 20 is arranged at the rotation center, and the number of the transfer assemblies 220 is two, wherein the motion track of one transfer assembly 220 forms a first projection at the rotating disc 210, the motion track of the other transfer assembly 220 forms a second projection at the rotating disc 210, and the first projection and the second projection are connected into a same straight line at the relay station 214. The incubation position 213, the wash separation and measurement position 211 are arranged on the same rotating disc 210.

When the measurement is completed, the waste liquid in the reactor 20 is first sucked, and the reactor 20 from which the waste liquid is sucked is discarded.

Referring to the reagent aspiration method, when the blending assembly 120 is at the second station 12, the reagent is aspirated from the storage unit 320 by the reagent pipetting unit 310 and is added to the reactor 20, and the reagent aspiration comprises the following sub-steps:

a reagent pipetting unit 310 and at least two storage units 320 for storing reagents are provided, and the reagents are contained in reagent containers on a plurality of storage sections 321 of the storage unit 320.

The storage section 321 is moved to follow the storage unit 320, and the reagent pipetting unit 310 pipettes a reagent in a reagent container arriving at the storage section 321 of the pipetting station 14.

The shortest time window for making the action sequence or task executed by each storage unit 320 recurable circularly is equal to the first period, i.e. the smallest time interval for the storage unit 320 to execute the same action twice in succession is equal to the first period. From the time when one of the storage units 320 first drives the reagent to move toward the pipetting station 14, the other storage units 320 are sequentially driven to move toward the corresponding pipetting station 14 by staggering the time interval of a second period.

In some embodiments, when the speed of movement of the storage unit 320 does not become a bottleneck in the throughput of the immunoassay analyzer, the aspiration of the reagent comprises the following sub-steps:

The operation sequences of the plurality of storage units 320 are synchronized in series, that is, the operation sequences of the plurality of storage units 320 in the work cycle are synchronized, and in series between the work cycles, each storage unit 320 can position the target storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent in each work cycle, but only one storage unit 320 is required to position the target storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent in each work cycle. In any case, in any cycle, one of the storage units is caused to position the storage section 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent.

All reagent components required for the corresponding analysis items are contained in the same storage unit 320. The number of reagent pipetting units 310 and storage units 320 is equal, and each storage unit 320 corresponds to one reagent pipetting unit 310.

Referring to the dilution method described above, when sample dilution is required, a diluent is added to the sample in the reactor 20 for dilution to form a diluted sample before other reagent components, other than the diluent components, are added to the reactor 20 at the second station 12.

For a single reactor 20, the work flow on the immunoassay analyzer 10 is as follows, taking the one-step test as an example: first, empty and clean reactor 20 is placed from a supply tray by transfer assembly 220 onto blending assembly 120 at initial station 13; secondly, the transportation assembly 110 drives the blending assembly 120 to move to the first station 11, and the sample pipetting unit 411 adds a sample to the reactor 20 at the first station 11; thirdly, the transportation assembly 110 drives the blending assembly 120 to move to the second station 12, the reagent pipetting unit 310 adds the reagent into the reactor 20 located at the second station 12, and the blending assembly 120 blends the sample and the reagent in the reactor 20; fourthly, the transferring component 220 transfers the reactor 20 after the blending treatment from the blending component 120 to the incubation position 213 of the rotating disc 210 through the incubation in-out station 15; fifth, after incubation, transfer module 220 moves reactor 20 from incubation position 213 at incubation in-out station 15 and from wash transfer station 16 to wash position 212 on carousel 210; sixthly, after the cleaning and separation are finished, adding a signal reagent into the reactor 20, moving the reactor 20 out of the cleaning position 212 at the cleaning and moving-out position 17 by the transfer component 220, putting the reactor into the signal reagent blending unit 430 for blending, transferring the reactor after the signal reagent blending is finished to the measuring position 211 of the rotating disc 210 from the measuring in-out position 18 by the transfer component 220, and measuring the optical signal in the reactor 20 by the measurer 230; sixthly, waste liquid in the reaction after the measurement is finished is absorbed by the waste liquid absorption component 240; seventh, transfer assembly 220 moves reactor 20 from measurement access station 18 out of rotating disk 210 and discards reactor 20 to a discard station.

When the delayed one-step test and the two-step test are performed, the transfer component 220 may move the incubated or cleaned reactor 20 into the mixing component 120 of the mixing device 100 again, add the second reagent and mix the mixture, and after the mixing is completed, the transfer component 220 moves the mixed reactor 20 into the reaction device 200 to perform the incubation, cleaning, separation and measurement.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. A method of dilution comprising the steps of:

the diluted sample and reagent components in the second reactor are mixed well.

2. The dilution method of claim 1, wherein the homogenizing assembly is cyclically reciprocated between an initial station, in which the first and second reactors are moved into and out of the homogenizing assembly, a first station, and a second station.

3. The dilution method defined in claim 2, wherein the initial station, the first station and the second station are positioned in a common line with the initial station being between the first station and the second station.

4. The method of dilution according to claim 1, wherein both the diluent and the reagent component are placed on the same storage unit.

5. The method of claim 1, wherein after the portion of the diluted sample is added to the second reactor, the first reactor is removed from the homogenizing assembly and discarded.

6. The dilution method according to claim 1, wherein the homogenizing assembly homogenizes the sample and the diluent in the first reactor and the diluted sample and the reagent components in the second reactor by non-contact eccentric oscillation.

7. The dilution method according to claim 1, wherein the number of kneading modules is at least two.

8. A dilution apparatus having a first station and a second station, comprising:

a transport assembly;

9. The dilution apparatus according to claim 8, wherein the pipetting assembly comprises a sample pipetting unit for pipetting samples and diluted samples and a reagent pipetting unit for pipetting diluent and reagent components.

10. The dilution apparatus of claim 8, wherein the blending assemblies are at least two in number.

11. The dilution apparatus according to claim 8, wherein the number of the transportation assemblies is one, and the transportation assemblies synchronously drive all the blending assemblies to circularly reciprocate between the first station and the second station.

12. The dilution apparatus defined in claim 8 wherein there are two transport assemblies, each transport assembly carrying a reactor of the blending assembly, each transport assembly driving the blending assembly to reciprocate cyclically between the first and second stations.

13. An immunoassay analyzer comprising the dilution apparatus of any one of claims 8 to 12.