CN111122883B

CN111122883B - Reaction device and immunoassay instrument

Info

Publication number: CN111122883B
Application number: CN201811277576.7A
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: 2023-08-08
Anticipated expiration: 2038-10-30
Also published as: CN111122883A

Abstract

A reaction apparatus comprising: -a rotating disc (210), said rotating disc (210) being used for incubating, washing and measuring reactants in said reactor (20); a washing unit (250) which is located above the rotating disk (210) and can inject washing liquid into the reactor (20) and extract unbound components, the washing unit (250) comprising a signal-injecting reagent section for injecting signal reagent into the reactor (20) after washing separation; a signal reagent mixing unit (430) for mixing the signal reagent into the reactor (20) after adding the signal reagent; a measuring device (230) connected to the rotating disk (210) for measuring an optical signal of the reactant in the reactor (20) after the addition of the signal reagent; and a transfer unit (220) capable of transferring the reactor (20) between the rotating disk (210) and the signal reagent mixing unit (430).

Description

Reaction device and immunoassay instrument

Technical Field

The invention relates to the technical field of in-vitro diagnosis, in particular to a reaction device and an immunoassay instrument.

Background

The full-automatic immunoassay analyzer can quantitatively or qualitatively detect target analytes such as antibodies and antigens contained in a sample to be detected by blood, generally, an empty reactor is added with the sample to be detected and a reagent (or referred to as a reactant), and after steps such as mixing, incubation, washing separation (Bound-free, BF separation, sometimes abbreviated as washing herein) and the like, a signal reagent is added into the reactor to measure optical signals or electrical signals, thereby realizing measurement and analysis of the target analytes contained in the sample to be detected.

For the traditional immunity analyzer, the whole immunity analyzer has the defect of insufficient compact structure due to the large volume of the reaction device.

Disclosure of Invention

One technical problem to be solved by the present invention is how to improve the structural compactness of the reaction apparatus.

A reaction apparatus comprising:

a rotating disc for incubating, washing and measuring reactants in the reactor;

the cleaning assembly is positioned above the rotating disc and can be used for injecting cleaning liquid into the reactor and extracting waste liquid, and comprises a signal injection reagent part for injecting signal reagent into the reactor after cleaning and separation;

the signal reagent mixing unit is used for uniformly mixing the signal reagent in the reactor after the signal reagent is added;

a measurer connected with the rotary disk and used for measuring optical signals of reactants in the reactor after the signal reagent is added; a kind of electronic device with high-pressure air-conditioning system

And the transferring assembly can transfer the reactor between the rotating disc and the signal reagent mixing unit.

In one embodiment, the reactor containing the signal reagent is mixed by eccentric shaking.

In one embodiment, the signal agent is mixed for a period of 2-6 seconds.

In one embodiment, the rotating disk has an incubation ring, a washing ring and a measuring ring arranged around the rotation center, wherein the incubation ring is provided with incubation positions for incubating reactants in the reactor at intervals along the circumference of the incubation ring, the washing ring is provided with washing positions for washing the reactants in the reactor at intervals along the circumference of the washing ring, and the measuring ring is provided with measuring positions for measuring the signals of the reactants in the reactor at intervals along the circumference of the washing ring; the transfer assembly transfers the reaction container among the signal reagent mixing unit, the incubation position, the cleaning position and the measuring position, and the movement track of the transfer assembly is positioned on the same straight line.

In one embodiment, an incubation in-out station, a cleaning out-out station and a measurement in-out station are provided; the incubation and access station is used for allowing the reactor to enter and exit the incubation position, the cleaning and moving-in station is used for allowing the reactor to move into the cleaning position, the cleaning and moving-out station is used for allowing the reactor to move out of the cleaning position, the measurement and access station is used for allowing the reactor to enter and exit the measurement position, and the transfer assembly moves among the incubation and access station, the cleaning and moving-in station, the cleaning and moving-out station and the measurement and access station.

In one embodiment, the transfer assembly moves the reactor containing the signal reagent from the incubation access station out of the wash station and into a signal reagent mixing unit.

In one embodiment, the transfer assembly moves the reactor after completion of signal reagent mixing out of the signal reagent mixing unit and into the measurement site from the measurement access station.

In one embodiment, the incubation ring, the cleaning ring and the measuring ring are sequentially arranged around the rotation center at intervals from inside to outside.

In one embodiment, the device further comprises a waste liquid sucking component, which is positioned above the measuring ring of the rotating disk and is used for sucking out signal reagents in the reactor after measurement.

An immunoassay device comprising any one of the above reaction devices.

One technical effect of one embodiment of the present invention is: the cleaning component not only can inject cleaning liquid and extract waste liquid, but also comprises a signal reagent injection part for injecting signal reagents, and meanwhile, the signal reagent mixing unit is further arranged, so that the reaction device has the functions of injecting and mixing the signal reagents, the whole reaction device is compact in structure, the moving distance of the transfer device between the rotating disc and the signal reagent mixing unit is short, and the moving speed of the transfer component is improved, so that the requirement of test flux is met.

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 mixing device in fig. 1;

fig. 3 is a schematic plan view of an immunoassay device according to a second embodiment;

fig. 4 is a schematic perspective view of the mixing device in fig. 3;

FIG. 5 is a flow chart of a serial 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 flow chart of a reagent sucking method according to an embodiment;

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

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

Detailed Description

In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. The drawings illustrate preferred embodiments of the invention. 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 "fixed 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 are used herein for illustrative purposes only and do not represent the only embodiment.

Incubation of sample reagents (or reactants) refers to the process of antigen-antibody binding reaction or biotin-avidin binding reaction of the reactants in a isothermal environment before the reactor starts to be washed (washing separation). The reagents and analysis items described herein are in a "one-to-one" relationship, i.e., the specific reagents corresponding to different analysis items generally differ in terms of formulation, amount of reagents, number of components, etc. Depending on the specific analysis, the reagent typically comprises a plurality of components, such as the usual 2-5 components, including magnetic particles, enzyme labels, diluents, dissociating agents, etc., e.g. the T4 reagent (thyroxine) comprises three components, magnetic particles, enzyme labels, dissociating agents. Depending on the reaction mode, the plurality of reagent components of one analysis item may be dispensed at one time or in a plurality of steps, and the step of dispensing may be defined as a first reagent, a second reagent, a third reagent, and the like in the order of dispensing. After incubation, washing separation is performed, which means a process of capturing the bound complex of the magnetic particles, antigen and labeled antibody with a magnetic field and simultaneously removing the Free (Free) labeled antibody and other unreacted or bound components (herein, expressed conveniently, simply referred to as unbound components). After washing and separation, the signal reagent is dispensed, signal incubation is performed (typically 1-6 minutes), and finally the amount of luminescence generated by the reaction of the labeled reagent with the signal reagent (referred to herein for convenience as a reactant signal) is measured. The signal reagent is used for generating a measurement signal (usually, luminescence), and is usually one of general-purpose reagents, and the signal reagent is shared by different analysis items in a corresponding relation of 'one-to-many' analysis items. Signal incubation refers to the process of enhancing the signal by allowing the reaction of the separated reactor after addition of the signal reagent for a period of time in a constant temperature environment. It should be noted that, due to the different specific components of the signaling agent, some light emitting systems do not require signaling and can be directly measured during or after dispensing of the signaling agent. The signaling agent may 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 labeling agent is quantitatively or qualitatively measured by the above-described procedure. Furthermore, the immunoassay analyzer can perform analysis corresponding to several different analysis items on the sample.

A work cycle or cycle, or cycle for short, is a cyclically recurring shortest time window during a test, which generally has a fixed length of time, during which a certain number of process operations, tasks or work packages, etc., such as operations and tasks of liquid extraction, mixing, incubation, wash separation, measurement, etc., are performed serially or in parallel in a controlled order. Tasks of the same component in one cycle are usually executed serially, and tasks of different components in the same cycle can be executed serially or in parallel depending on whether there is a dependency between actions of related components. All process operations performed in one cycle are performed only when needed and do not have to be repeated in another cycle. In particular, certain process operations may occur repeatedly in each cycle, while others may occur once every two or more cycles. When multiple tests are performed in succession, only some of the process operations are dedicated to performing one test and others are dedicated to performing the other test, i.e., different process operations are dedicated to different tests, respectively, in a single cycle, since each test is typically in a different stage of the test process, all of the process operations occurring in the single cycle. Thus, testing is typically accomplished in multiple cycles, wherein different process operations for performing the test occur in different cycles. In order to improve the test efficiency and throughput, for the components with speed bottlenecks, the number of the components can be increased and the period of the components can be prolonged, so that the working periods of different components are not necessarily the same, that is, a plurality of parallel periods may exist in the same system, and usually, the time lengths of the parallel periods have a multiple relationship, and the multiple is usually equal to the number of the same components. When two working periods exist, the two working periods are respectively called a first period and a second period, for example, when the number of the reagent pipetting units is N (N is larger than or equal to 2 and is a natural number), each reagent pipetting unit works in the first period, the length of the first period is N times that of the second period, and the action sequences of the N reagent units are continuously staggered and parallel to the second period. The invention can realize high-flux immune test, the typical second period length is 4-15 seconds, the corresponding test flux is 900-240 tests per hour, namely 900-240 results can be continuously reported per hour.

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 empty reactor 20, the sample supply device 410 is used for adding a sample into the empty reactor 20, the reagent supply device 300 is used for adding a reagent into the reactor 20 containing the sample, the mixing device 100 is used for mixing 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 mixing treatment in the reactor 20.

In some embodiments, the reactor feeder 420 includes a feed bin, a sequencing mechanism, a feed slide, and a feed tray. The supply bin is used for storing clean and empty reactors 20, the supply bin can be positioned at the rear of the reagent supply device 300, so that the whole machine space can be fully utilized, the structure of the immunoassay analyzer 10 is more compact, the sequencing mechanism is used for arranging the randomly placed reactors 20 in order, the supply slide ways are used for guiding the sequenced reactors 20 into the supply tray one by one, the supply tray is used for buffering the reactors 20 conveyed by the supply slide ways, 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, and the reactors 20 are driven to a specified position, which can be defined as a reactor supply station, and the reactors 20 on the supply tray are transferred to the mixing device 100 at the reactor supply station.

In some embodiments, the sample supply 410 includes a sample rack, a sample tube, a transport rail, a sample pipetting unit 411, and the like. The sample racks may cooperate with the transport track, and sample tubes may be placed on the sample racks for holding samples, e.g., five to ten or so sample tubes may be placed on each sample rack. When the sample rack moves the sample tube to a designated position along the transport rail, the sample pipetting unit 411 aspirates the sample of the sample tube and adds the sample to the empty reactor 20. The sample pipetting unit 411 may adopt a steel needle or a disposable suction nozzle, and in order to realize smooth suction of the sample, the sample pipetting unit 411 may perform a motion form such as vertical up-down motion, horizontal linear motion or horizontal rotation.

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

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

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

Each mixing assembly 120 includes a support 121, a drive 123, and a carrying stage 122, the support 121 being slidably disposed on the frame 111 and coupled to the conveyor of the transport assembly 110. Specifically, a sliding rail can be disposed on the frame 111, the support 121 is matched with the sliding rail, the synchronous belt 112 drives the support to slide along the extending direction of the sliding rail, the driver 123 is mounted on the support 121 and connected with the bearing platform 122, the bearing platform 122 is used for placing the reactor 20, the synchronous belt 112 can drive the support 121 on each mixing assembly 120 to move in the same direction, and the driver 123 can drive the bearing platform 122 to generate eccentric oscillation, so that reactants in the reactor 20 are mixed due to non-contact eccentric oscillation.

At least two receiving holes 122a may be provided on the susceptor 122, and the reactor 20 is inserted into the receiving holes 122a, thereby achieving a loading effect of the susceptor 122 on the reactor 20. Of course, the receiving hole 122a may be replaced by a solid structure such as a bracket, so long as the reactor 20 can be placed on the susceptor 122.

When the number of mixing assemblies 120 is two, one mixing assembly 120 includes a first support 1211 and a first carrier 1221, and the other mixing assembly 120 includes a second support 1212 and a second carrier 1222, the first support 1211 having a first mounting end 1211a and the second support 1212 having a second mounting end 1212a, the second mounting end 1212a being disposed proximate to the first mounting end 1211 a. The first stage 1221 is positioned at the first mounting end 1211a and the second stage 1222 is positioned at the second mounting end 1212 a. In short, the first stage 1221 and the second stage 1222 are positioned opposite each other so that samples and reagents can be added to the reactor 20 on different stages 122 at designated locations.

Referring to fig. 5, when the above-mentioned serial mixing device 101 is used to mix a sample and a reagent, a serial mixing method may be formed, and the serial mixing method mainly includes the following steps:

s510, providing at least two mixing assemblies 120 for carrying the reactor 20, and synchronously driving the mixing assemblies 120 to circularly reciprocate between the first station 11 and the second station 12 by adopting the same conveying assembly 110; i.e. the timing belt 112 drives all the carrying platforms 122 to move between the first station 11 and the second station 12.

S520, adding a sample to the reactor 20 at the first station 11, adding a reagent to the reactor 20 at the second station 12, and uniformly mixing the sample and the reagent in the reactor 20. When the timing belt 112 drives the carrying stage 122 to move to the first station 11, the timing belt 112 stops moving, and since the sample pipetting unit 411 is disposed near the first station 11, the sample pipetting unit 411 will aspirate and add the sample to one of the reactors 20; after the sample is added, when the synchronous belt 112 drives the carrying table 122 to move to the second station 12, the synchronous belt 112 stops moving, and the reagent can be added into the reactor 20 containing the sample through 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 can drive the bearing table 122 to generate eccentric vibration, so as to uniformly mix the sample and the reagent in the reactor 20 in a non-contact eccentric vibration mode.

S530, the action sequence or task executed by the mixing component 120 comprises the actions of moving into the reactor 20, receiving the sample added by the sample pipetting unit 411, receiving the reagent added by the reagent pipetting unit 310, eccentrically oscillating, moving out of the reactor 20 after the mixing is completed, and the like, and the shortest time window which can be circularly reproduced is recorded as a first period, namely the minimum time interval of continuously executing the same action twice by the mixing component 120 is recorded as the first period. The value obtained by dividing the first period by the number of blending elements 120 is referred to as the second period. From the first time of transferring one of the mixing assemblies 120 into the reactor 20, the time interval of one second period is sequentially staggered, and then each of the other mixing assemblies 120 is transferred into the reactor 20. It will be appreciated that to achieve the above steps, the duty cycle of the transport assembly 110 is the second period, and the duty cycle of the blending assembly 120 is the first period. The transport assembly 110 may synchronously drive the blending assembly 120 to reciprocate cyclically between the first station 11 and the second station 12 during each second cycle.

And S540, sequentially shifting the uniformly mixed reactors 20 out of the mixing assembly 120 by a time interval of one second period, and shifting a new reactor 20 on the mixing assembly 120 which is shifted out of the reactors 20.

The present invention allows for high throughput immunoassay, 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, etc., with a corresponding throughput of 900-240 tests per hour, i.e., 900-240 results can be reported continuously per hour.

The following description will take 10 seconds as an example for convenience of description.

In the following, the description will be given by taking the example that the transporting assembly 110 drives the two mixing assemblies 120 to move synchronously, and if the immunoassay analyzer 10 has to complete the measurement of one reactor 20 every 10 seconds, i.e. report a test result every 10 seconds, the time of the second period is 10 seconds. Regarding the whole immunoassay analyzer 10 as a flow line, it is necessary to ensure that the flow rates are equal throughout the flow line, and thus the mixing device 100 must output a mixed reactor 20 at intervals of 10 seconds. If there is only one mixing assembly 120, since the sum of the time required for moving the mixing assembly 120 into the reactor 20, receiving the sample from the sample pipetting unit 411, receiving the reagent from the reagent pipetting unit 310, adding the reagent, eccentrically vibrating and mixing, moving out the mixed reactor 20, etc. is more than 10 seconds, which is performed in one cycle, the mixing device 100 cannot output a mixed reactor 20 every 10 seconds, and the flow rate of the mixing device 100 is lower than the outlet flow rate of the flow line, so that the flow line cannot continuously operate with maximum efficiency. Therefore, by setting the first period to be twice the second period, that is, the first period is 20 seconds, and simultaneously making the number of the mixing assemblies 120 be two, the action sequences executed by the two mixing assemblies 120 are executed with respect to each other staggered by the time of the second period (that is, 10 seconds), that is, the two mixing assemblies 120 are separated by one second period and are "staggered in parallel", on the basis that each mixing assembly 120 outputs one mixed reactor 20 every 20 seconds, the whole mixing device 100 outputs one mixed reactor 20 every 10 seconds, and finally, the purpose of "number change time" is achieved.

Of course, the initial station 13 may also be provided, so that the transporting assembly 110 drives the mixing assembly 120 to circularly reciprocate among the initial station 13, the first station 11 and the second station 12; at the initial station 13, the reactor 20 is moved into or out of the blending assembly 120. The initial station 13, the first station 11 and the second station 12 may be disposed 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 track of the mixing assembly 120 between 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 disposed on the same circumference such that the blending assembly 120 moves circumferentially between the initial station 13, the first station 11, and the second station 12. Compared with the traditional mixing assembly 120 which is fixed at a single station, the transportation assembly 110 drives the mixing assembly 120 to circularly reciprocate among a plurality of stations, so that the mixing assembly 120 orderly completes 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 of the reactor 20, such as tasks of receiving the reactor 20, receiving samples, reagents, mixing and the like, can be realized, and the test flux of the whole machine is improved.

Specifically, when the in-line mixing apparatus 101 starts to operate, one reactor 20 is first added to the first stage 1221 at the initial station 13, and at this time, no reactor 20 is added to the second stage 1222; the conveyor drives the first stage 1221 and the second stage 1222 from the initial station 13 to the first station 11, adding samples to the reactor 20 on the first stage 1221; the conveyor drives the first stage 1221 and the second stage 1222 from the first station 11 to the second station 12, adding reagents to the reactor 20 with the sample on the first stage 1221; the first bearing table 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 and second carriages 1221, 1222 back from the second station 12 to the initial station 13, at which point the first and second carriages 1221, 1222 arrive at the initial station 13 at the 10 th second, adding the reactor 20 to the second carriage 1221 for the first time; the conveyor drives the first stage 1221 and the second stage 1222 from the initial station 13 to the first station 11 again, adding samples to the reactor 20 on the second stage 1222; the conveyor drives the first stage 1221 and the second stage 1222 from the first station 11 to the second station 12 again, adding reagents to the reactor 20 with the samples on the second stage 1222; the second carrying table 1222 generates eccentric oscillation to make the sample and reagent in the reactor 20 begin to mix uniformly; the conveyor drives the first and second carriages 1221, 1222 back from the second station 12 to the initial station 13, at which point the first and second carriages 1221, 1222 arrive at the initial station 13 at the 20 th second, are added to the reactor 20 a second time on the first carriage 1221, and move toward the first station 11. According to this mixing law, when the first and second stages 1221 and 1222 reach the initial station 13 at 20 seconds, the reactor 20 is added a second time on the second stage 1222. By analogy, when the first stage 1221 and the second stage 1222 reach the initial station 13 at 20 seconds, 30 seconds, and 10N seconds (n+.2), the reactor 20 moves into the mixing device 100. Similarly, since the working cycle of each mixing assembly 120 is the first cycle (20 seconds) and the motion sequence between the mixing assemblies 120 is staggered in parallel by the second cycle (10 seconds), each mixing assembly 120 completes one reactor 20 for mixing treatment every 20 seconds and moves out of the mixing device 100 into the reaction device 200, but the whole mixing device 100 outputs one reactor 20 for mixing treatment 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 mixing while fully utilizing the mixing time, the reactor 20 on the other mixing assembly 120 is adding the sample or reagent, thereby allowing the flow rate of the entire mixing apparatus 100 to meet the test throughput requirements.

Of course, the time of the first period may also be longer when the second period is still 10 seconds, at which time the number of mixing assemblies 120 is made three, four or more, the first period may be set to three, four or more times the second period, i.e., the first period is 30 seconds or 40 seconds or the like. On the basis of guaranteeing the test flux, the movement speed of the transport assembly 110 can be reduced, the mixing time of the sample and the reagent is prolonged, and the movement speed bottleneck of the transport assembly 110 and the mixing time bottleneck of the sample and the reagent are effectively solved. Under the condition that the movement speed of the transporting component 110 and the mixing time of the sample and the reagent are fixed, each mixing component 120 still outputs a reactor 20 after the mixing treatment is finished every 20 seconds, namely, the first period is still 20 seconds, if the test flux of the immunity analyzer 10 needs to be improved, for example, a measured reactor 20 is required to be output every 5 seconds (the second period), the mixing components 120 on the transporting component 110 can be increased to four; as another example, the mixing assembly 120 on the transport assembly 110 may be increased to five by requiring one measured reactor 20 to be output every 4 seconds (second cycle).

At least two mixing positions may be disposed in each mixing assembly 120, where a mixing position is a receiving hole 122a on the carrying table 122, and when one mixing position (receiving hole 122 a) is occupied by a reactor 20 that is being mixed or is completed to be mixed, the reactor 20 is moved into another idle mixing position (receiving hole 122 a) on the mixing assembly 120. This can solve the problem of mixing site occupation during the process of moving the reactor 20 in and out on the same carrier 122, and improve the test efficiency and test throughput.

The mixing of the sample and the reagent in the reactor 20 may be performed after the transportation assembly 110 drives the mixing assembly 120 to stop, or may be performed during the movement, for example, when the mixing assembly 120 returns from the second station 12 to the initial station 13, the driver 123 makes the carrying platform 122 generate eccentric oscillation to mix the sample and the reagent. The mixing process during the movement can fully utilize the time of the mixing assembly 120 during the movement to mix the sample and the reagent, so as to ensure that the mixing device 100 meets the test flux requirement.

The time required from the beginning of mixing to the completion of mixing of the sample and reagent loaded reactor 20 is typically 2-10 seconds, the working cycle of transport assembly 110 is a first cycle, and the two mixing assemblies 120 are a second cycle, so that there is enough time for the sample and reagent to mix, ensuring that the sample and reagent can react sufficiently, and improving the accuracy of the subsequent measurement results.

Referring to fig. 3 and 4, in some embodiments, the mixing device 100 is a parallel type mixing device 102 including at least two mixing mechanisms 103, each mixing mechanism 103 including a transporting assembly 110 and a mixing assembly 120, the mixing assembly 120 being disposed on the transporting assembly 110, the transporting assembly 110 driving the mixing assembly 120 to move. For example, where each blending mechanism 103 includes a transport assembly 110 and a blending assembly 120, the strokes of the blending assemblies 120 are in parallel relationship to one another. The structures of the transporting assembly 110 and the mixing assembly 120 are the same as the corresponding structures in the serial mixing device 100, that is, each transporting assembly 110 includes a frame 111 and a conveyor disposed on the frame 111, and each mixing assembly 120 includes a support 121, a driver 123 and a bearing platform 122, which are not described herein. The main differences with the serial mixing device 100 are that: the blending assemblies 120 are disposed on different transport assemblies 110, respectively, and the motions of the blending assemblies 120 on different transport assemblies 110 are not synchronized.

In some embodiments, at least one mixing mechanism 103 includes a transporting assembly 110 and at least two mixing assemblies 120, where the transporting assembly 110 drives the at least two mixing assemblies 120 to move synchronously, at this time, at least two mixing assemblies 120 on the mixing mechanism 103 are connected in series, and the mixing assemblies 120 on the mixing mechanism 103 are connected in parallel with the mixing assemblies 120 on the other mixing mechanism 103, that is, the mixing assemblies 120 in the whole mixing device 100 have a parallel and serial (i.e., parallel-parallel) relationship.

Referring to fig. 6, when the above-mentioned parallel mixing device 102 is used to mix the sample and the reagent, a parallel mixing method may be formed, and the parallel mixing method mainly includes the following steps:

at S610, at least two transport assemblies 110 are provided, such that each transport assembly 110 is provided with a mixing assembly 120 for carrying the reactor 20, and each transport assembly 110 drives the mixing assembly 120 to reciprocate cyclically between the first station 11 and the second station 12.

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

S630, the action sequence or task executed by the mixing component 120, including the actions of moving into the reactor 20, receiving the sample from the sample pipetting unit 411, receiving the reagent from the reagent pipetting unit 310, adding the reagent, eccentrically oscillating, moving out of the reactor 20 after the mixing is completed, is recorded as the first period, i.e. the minimum time interval between two consecutive actions of the mixing component 120 is the first period. The value obtained by dividing the first period by the number of blending elements 120 is referred to as the second period. The mixing assemblies 120 on one of the transport assemblies 110 are sequentially moved into the reactor 20 at intervals offset by a second period from the first movement of the mixing assemblies 120 on the other transport assembly 110. It will be appreciated that to achieve the above steps, the duty cycle of each of the transport assembly 110 and blending assembly 120 is a second cycle.

And S640, sequentially shifting the uniformly mixed reactors 20 out of the mixing assembly 120 by a time interval of one second period, and placing a new reactor 20 on the mixing assembly 120 which is shifted out of the reactors 20.

The following description will take two transportation assemblies 110, and each transportation assembly 110 is provided with a blending assembly 120 as an example, and the same points as the serial blending method are referred to above. Assuming that the second period is 10 seconds, and each mixing mechanism 103 outputs a mixed reactor 20 every 20 seconds, that is, the first period is 20 seconds, because the time (10 seconds) between the second periods is staggered in sequence, the mixed reactors 20 are moved onto the mixing assemblies 120 on the other transporting assemblies 110, and finally, the whole mixing device 100 outputs a mixed reactor 20 every 10 seconds, which can also play the role of 'number changing time'.

Referring to the description of the series type mixing method, in the parallel type mixing method, the initial station 13 may be also set, so that the transporting assembly 110 drives the mixing assembly 120 to circularly reciprocate among the initial station 13, the first station 11 and the second station 12; at the initial station 13, the reactor 20 is moved into or out of the blending assembly 120. The initial station 13, the first station 11 and the second station 12 may be disposed 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 track of the mixing assembly 120 between the initial station 13, the first station 11 and the second station 12 is a straight line.

Compared with the traditional mixing assembly 120 which is fixed at a single station, the conveying assembly 110 drives the mixing assembly 120 to circularly reciprocate among a plurality of stations, so that the test flux of the whole machine is improved.

Each mixing assembly 120 is provided with at least two mixing positions, namely, the mixing positions are containing holes 122a on the bearing table 122, and the two mixing positions are used simultaneously or alternately, so that the treatment efficiency of the mixing assembly 120 on the reactor 20 can be improved. When one of the mixing locations (receiving aperture 122 a) is occupied, the reactor 20 may be moved into the other mixing location (receiving aperture 122 a) on the mixing assembly 120. The sample and the reagent in the reactor 20 can be uniformly mixed during the process of driving the mixing assembly 120 by the transporting assembly 110 or after stopping the movement, that is, the mixing of the sample and the reagent in the reactor 20 is not limited by the movement state of the transporting assembly 110, so that the mixing device 100 is more flexible and efficient.

Specifically, when the parallel mixing device 100 starts to operate, one of the transport assemblies 110 is denoted as a first transport assembly 1101, and the other transport assembly 110 is denoted as a second transport assembly 1102. One reactor 20 is first added to the load-table 122 on the first transport assembly 1101 at the initial station 13, while the load-table 122 on the second transport assembly 1102 is not added to the reactor 20.

For the first transport assembly 1101, as it moves from the initial station 13 to the first station 11, a sample is added to the reactor 20 on the carrier 122 of the first transport assembly 1101; the first transport assembly 1101 moves from the first station 11 to the second station 12 and reagent is added to the reactor 20 on the stage 122 of the first transport assembly 1101 that holds the sample; the carrier 122 of the first transport assembly 1101 produces an eccentric oscillation that causes the sample and reagents in its reactor 20 to begin to mix.

For the second transport assembly 1102, 10 seconds after the reactor 20 is first added to the load-carrying stage 122 on the first transport assembly 1101, the reactor 20 is first added to the load-carrying stage 122 on the second transport assembly 1102, and the second transport assembly 1102 is caused to start moving according to the movement law of the first transport assembly 1101. By analogy, both the susceptor 122 on the first transport assembly 1102 and the susceptor 122 on the second transport assembly 1102 will have the reactor 20 moved into the mixing apparatus 100 when the 20 th, 30 th, 10 nth seconds reach the initial station 13. Similarly, since the working cycle of each mixing module 120 is the first cycle (20 seconds) and the motion sequence between the mixing modules 120 is staggered in parallel by the second cycle (10 seconds), each mixing module 120 completes one reactor 20 for mixing treatment every 20 seconds and moves out of the mixing apparatus 100 into the reaction apparatus 200, but the whole mixing apparatus 100 outputs one reactor 20 for mixing treatment every 10 seconds.

For the parallel type mixing method, the transportation assembly 110 drives the mixing assembly 120 to be staggered and parallel at intervals of one second period (10 seconds), and although each mixing mechanism 103 outputs one mixed reactor 20 at intervals of 20 seconds (first period), two mixing mechanisms 103 are staggered for 10 seconds to start to operate from the initial station 13, so that the whole mixing device 100 outputs one mixed reactor 20 every 10 seconds (second period). By increasing the number of mixing mechanisms 103, the transport assembly 110 can move at a slower speed on the basis that the flow rate of the overall mixing apparatus 100 meets the test flux requirements, solving the speed bottleneck of movement of the transport assembly 110 and the mixing time bottleneck between the sample and the reagent. For other similarities, reference is made to the description of the series blending method described above.

When the number of the mixing assemblies 120 arranged on the at least one transporting assembly 110 is not less than two, the transporting assembly 110 drives all the mixing assemblies 120 arranged thereon to move synchronously, that is, the at least one mixing mechanism 103 comprises at least two mixing assemblies 120, the mixing assemblies 120 on the mixing mechanism 103 are in a serial connection, so that the mixing assemblies 120 on the whole mixing device 100 have a parallel connection and a serial connection at the same time, and similarly, each mixing assembly 120 is added into the reactor 20 for the first time at intervals of one second period, and finally, the whole mixing device 100 outputs a mixed reactor 20 at intervals of one second period. By arranging the partial mixing assemblies 120 in series, the overall mixing apparatus 100 may 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 placed 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 into the reactor 20 at the second station 12. The number of the storage parts 321 may be set according to the need, and in consideration of 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 the two storage units 320 can simultaneously store 50 reagent containers on line. Each storage unit 320 stores all reagent components required for a corresponding analysis item, for example, in one analysis item, three reagent components including a magnetic particle, an enzyme label and a dissociation agent must be added to the reactor 20, and then the three components are stored in the same storage unit 320. When an analysis project requires loading of multiple reagent containers to extend the on-board test volume of the project, the multiple reagent containers may be stored in each storage unit in any suitable combination. For example, when the number of storage units is 2, 3 TSH (thyroid stimulating hormone ) reagent containers each containing 100 tests need to be loaded, and all 3 TSH reagent containers can be loaded in the same storage unit, or 1 TSH reagent container can be loaded in one storage unit, and the other 2 TSH reagent containers can be loaded in the other storage unit.

For the conventional reagent supplying apparatus 300, in order to increase the storage amount 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 occupied area of the storage unit 320 is large, which is not conducive to the layout and production and manufacture of the storage unit 320, on the other hand, for the storage unit 320 having a large volume and weight, the difficulty of controlling the movement thereof is increased, which results in that the storage parts 321 cannot reach the designated position for the reagent pipetting unit 310 to aspirate the reagent in a short time, which becomes a bottleneck for realizing high test throughput. In addition, the conventional reagent supplying apparatus 300 stores a plurality of reagent components for the same analysis item on different storage units 320, so that not only the reagent pipetting unit 310 sucks the reagent for the same analysis item on a plurality of different storage units 320, resulting in a large stroke and complex movement logic of the reagent pipetting unit 310, but also the reagent components are required to be stored in a plurality of reagent containers, resulting in problems of high manufacturing cost, inconvenient operation of a user, and the like, and in addition, since a plurality of reagent components for the same analysis item are stored on different storage units 320, when a certain storage unit fails, the instrument is directly caused to be unable to continue the test.

The reagent supplying apparatus 300 of the above embodiment is provided with at least two storage units 320, and each storage unit 320 has a smaller volume, which is beneficial to overall layout and motion control, and also ensures a larger reagent storage capacity of the whole reagent supplying apparatus 300. Meanwhile, each storage unit 320 stores all reagent components required for the corresponding analysis item, so that the reliability and tolerance to faults of the reagent supply device 300 can be improved, and when one storage unit 320 fails and cannot work, the other remaining storage units 320 can continue to work, so that the reagent supply device 300 can still work effectively. Of course, the failed storage unit 320 may be refurbished while the other storage units 320 are operating.

The storage unit 320 may be a rotating disc, which periodically rotates intermittently, so as to drive the storage portion 321 to a designated position (i.e., the pipetting station 14), so that the reagent pipetting unit 310 sucks the reagent on the storage portion 321 at the pipetting station 14. The number of reagent pipetting units 310 may be equal to the number of rotating discs, one reagent pipetting unit 310 for each rotating disc, and each reagent pipetting unit 310 aspirates reagent from its corresponding rotating disc. Similar to the sample pipetting unit 411, the reagent pipetting unit 310 may use a steel needle or a disposable suction nozzle, and in order to achieve smooth suction of the reagent, the reagent pipetting unit 310 may perform a vertical up-and-down motion, a horizontal linear motion, or a horizontal rotation motion. Of course, the number of reagent pipetting units 310 may be one, and the one reagent pipetting unit 310 may aspirate the reagent in a plurality of rotating discs.

The reagent supplying apparatus 300 further includes a scanner provided on the storage unit 320, which can recognize bar code information of the reagent container on the storage portion 321, thereby distinguishing different reagents. To make the entire reagent feeding apparatus 300 compact, the scanner adopts a stationary arrangement. The storage unit 320 may further be provided with a refrigerator, which may perform a refrigerating process on the reagent in the storage unit 321, thereby realizing an online long-term storage of the reagent.

Referring to fig. 7, in order to achieve a high throughput immunoassay, when a reagent is suctioned using the reagent supplying apparatus 300 described above, a method of suctioning the reagent may be formed, which includes the steps of:

s710, providing a reagent pipetting unit 310 and at least two storage units 320 for storing reagents, storing reagent containers on the plurality of storage parts 321 of the storage units 320, so that each storage unit 320 stores all reagent components required for the corresponding analysis items.

S720, the storage portion 321 is moved along with the storage unit 320, so that the reagent pipetting unit 310 aspirates the reagent from the storage portion 321 reaching the pipetting station 14. The movement of the storage unit 320 may be a rotation, for example, the storage unit 320 may be intermittently rotated periodically, so that the storage portion 321 is reached at the pipetting station 14 at intervals of a set time, so that the reagent pipetting unit 310 may aspirate the reagent.

S730, the shortest time window in which the action sequence executed by each storage unit 320 can be cyclically reproduced is denoted as the first period, i.e. the smallest time interval in which the storage unit 320 executes the same action twice consecutively is denoted as the first period. The value obtained by dividing the first period by the number of memory cells 320 is denoted as the second period. From the time when one of the storage units 320 drives the storage portion 321 to move towards the liquid suction station 14 for the first time, the storage portions 321 are driven by the other storage units 320 to move towards the corresponding liquid suction stations 14 by sequentially staggering the time interval of a second period.

Taking two storage units 320 as an example, according to the principle that the flow rates are equal everywhere, the value of the second period is equal to the value of the second period mentioned in the above mixing method, and taking 10 seconds as an example, one storage unit 321 reaches the pipetting station 14 for each 10 seconds to suck the reagent by the reagent pipetting unit 310. Of course, the value of the first period is the same as the value of the first period mentioned in the above mixing method, that is, the value of the first period is 20 seconds. Referring to the basic principle of the above mixing method, two storage units 320 are separated by a second period and are "staggered and parallel", although each storage unit 320 will have one storage portion 321 reaching the corresponding pipetting station 14 every 20 seconds, the action sequence of the two storage units 320 is staggered for 10 seconds to start execution, so that each 10 seconds of the whole reagent supplying apparatus 300 will have one storage portion 321 reaching the pipetting station 14 for the reagent pipetting unit 310 to suck the reagent, by increasing the number of storage units 320 for exchanging time, the storage units 320 can be rotated at a slower speed on the basis that the flow rate of the whole reagent supplying apparatus 300 meets the test flux requirement, 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 whole reagent supplying apparatus 300 can be increased without changing the rotational speed of the storage units 320, thereby improving the test throughput of the immunoassay analyzer 10.

In some embodiments, if it is appropriate to reduce the immunoassay meter test throughput or to increase the movement speed of the storage units using other costly designs, the movement speed of the storage units 320 may not be a bottleneck to the immunoassay meter test throughput, the movement sequences of the plurality of storage units 320 may be "synchronized in series", i.e., the movement sequences of the plurality of storage units 320 are synchronized during a work cycle during which each storage unit 320 may position the target storage 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent, but only one storage unit 320 is required to position the target storage 321 to the pipetting station 14 for each work cycle for the reagent pipetting unit 310 to aspirate reagent. 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 illustrated as examples. At 10 seconds 1, one storage portion 321 of the first storage unit reaches the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; 10 seconds 2, one storage portion 321 of the second storage unit reaches the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; 10 seconds 3, one storage portion 321 of the first storage unit reaches the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent; according to this law, two storage units 320 are alternately connected in series every 10 seconds, and one storage unit 321 is reached to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent. Of course, the first storage unit may position the storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent at the 1 st, 2 nd, … nth 10 seconds (n+.1); the nth (n+1), … (n+m) th 10 seconds (m+.1), the second storage unit positions the storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate the reagent. In any case, the storage portion 321 may be positioned by one of the storage units to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent during any one of the work cycles.

For the same storage unit 320, all reagent components required for one test corresponding to the analysis item are stored, 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 supplying device 300 is improved. On the other hand, when the storage unit 320 fails, the instrument can use other storage units 320 to continue testing, so that normal performance of the instrument testing is not affected, and the tolerance to the failure is improved. In addition, all reagent components required for testing the corresponding analysis items are placed in the same storage unit 320, and can be contained in a reagent container with a plurality of reagent chambers, so that the production and manufacturing cost is saved, and the handling operation of users and the like is facilitated.

During the process that the storage portion 321 follows the storage unit 320 to rotate (revolve), at least one cavity (such as a magnetic particle cavity for containing a magnetic particle reagent component) of the reagent container on the storage portion 321 rotates around the central axis of the storage portion, so that the magnetic particle reagent component in the form of solid suspension is vortex, and solid substances (such as magnetic particles) in the magnetic particle reagent component are prevented from precipitating.

The plurality of storage units 320 are independently configured, i.e., each storage unit 320 can be independently rotated to position the reagent on the storage portion 321 to the pipetting station 14. It should be noted that "independent arrangement" herein is independent of the spatial arrangement and physical location between the storage units 320, e.g., multiple storage units 320 may be distributed on the instrument separately and without overlapping, or one storage unit 320 may be nested around or inside another storage unit 320. Of course, for better layout and control, it is preferable that the plurality of memory cells 320 be identically constructed and separately laid out. The plurality of storage units 320 are independently provided, which can improve flexibility of control, further improve efficiency of reagent supply, and thus improve throughput of the apparatus.

The number of reagent pipetting units 310 and the number of storage units 320 may be made equal, and each storage unit 320 corresponds to one reagent pipetting unit 310, i.e. each storage unit 320 is suctioned 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 flux, and the moving speed bottleneck of the reagent pipetting units 310 can be solved.

Referring to both fig. 1 and 3, in some embodiments, the reaction apparatus 200 includes a rotating disk 210, a transfer assembly 220, a measurer 230, and a cleaning assembly 250. The rotating disk 210 is provided with an incubation ring 203, a cleaning ring 202 and a measuring ring 201, the incubation ring 203, the cleaning ring 202 and the measuring ring 201 are all arranged around the rotating center of the rotating disk 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 sites 211, and the measuring sites 211 are arranged at intervals along the circumferential direction of the measuring ring 201. The incubation site 213, the washing site 212 and the measurement site 211 are used for placing the reactor 20, and the three may be slots or brackets or other structures suitable for carrying the reactor 20. The measurer 230 is connected to the rotating disk 210, and the measurer 230 can measure an optical signal of the reactor 20 after adding a signal reagent to realize further analysis of the reactant. The cleaning assembly 250 is located above the cleaning ring 202 and includes a liquid filling portion for filling the reactor 20 at the cleaning position 212 with cleaning buffer and a liquid suction portion which can be lowered and raised into and out of the reactor 20 at the cleaning position 212 to extract and remove unbound components from the reactor 20. Further, for simplicity, the cleaning assembly 250 further includes a signal reagent injection section for injecting a signal reagent into the separated reactor 20 cleaned at the cleaning station 212. In some embodiments, the reaction device 200 further includes a waste-absorbing assembly 240 and a signal reagent mixing unit 430. The waste liquid absorbing assembly 240 is located above the measuring ring 201, after the measurement of the reactor 20 is completed, the waste liquid absorbing assembly 240 can descend and ascend into and out of the reactor 20 on the measuring position 211, waste liquid (mainly signal reagent) in the reactor 20 is absorbed, and finally the reactor 20 after the waste liquid is absorbed is transferred to a discarding station, so that separate treatment of solid garbage and liquid garbage is realized, and the risk of biohazard is reduced. Further, the waste liquid sucking assembly 240 may be connected to the liquid sucking part of the cleaning assembly 250, and may be lowered to the bottom of the reactor together with the liquid sucking part of the cleaning assembly 250 to suck the liquid, and lifted off the reactor after the liquid sucking is completed. Thus, the functions of the cleaning assembly 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 the waste liquid sucking assembly are avoided. The signal reagent mixing unit 430 is provided independently of the rotary disk 210, and includes a mixing assembly similar to or identical to the aforementioned mixing assembly 120, and performs eccentric oscillation mixing on the reactor 20 containing the signal reagent.

The transfer assembly 220 removes the homogenized reactor 20 from the homogenizing apparatus 100 and moves it to the incubation site 213, and the incubation site 213 incubates the homogenized sample and reagent in the reactor 20 for a set time period while the reactor 20 follows the rotation of the rotating disk 210. After the incubation of the reactor 20 is completed, the transfer component 220 transfers the reactor 20 from the incubation position 213 to the cleaning position 212, the liquid injection portion of the cleaning component 250 can inject cleaning liquid into the reactor 20 located in the cleaning position 212 in the process of following the rotation of the rotating disk 210, then the magnetic particle compound is adsorbed on the inner side wall of the reactor 20 through a magnetic field, the liquid suction portion of the cleaning component 250 extracts unbound components from the reactor 20, and after a plurality of rounds of "injecting cleaning liquid-adsorbing-extracting unbound components", the cleaning separation of the reactants of the reactor 20 is completed. After the cleaning and separation of the reactants in the reactor 20 are completed, the signal reagent injection part may add a signal reagent into the reactor 20, and the transfer unit 220 transfers the reactor 20 to which the signal reagent is added from the cleaning position 212 to the signal reagent mixing unit 430, and mixes the signal reagent by the signal reagent mixing unit 430. In order to ensure that the signal reagent is fully and evenly mixed without influencing the test flux of the instrument, the mixing time of the signal reagent is 2-6 seconds. After the reactor 20 containing the signal reagent is mixed, the transfer component 220 transfers the reactor 20 from the signal reagent mixing unit 430 to the measurement position 211, if the signal incubation needs to be continued on the reactor 20 containing the signal reagent, the measurement position 211 can incubate the reactor 20 for a set time in the process that the reactor 20 follows the rotation of the rotating disc 210, and when the reactor 20 follows the rotation disc 210 to the position of the measurer 230, the measurer 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 measuring ring 201 are concentrically arranged, i.e. all the three take the rotation center of the rotary disk 210 as the center of circle. The incubation ring 203, the cleaning ring 202 and the measuring ring 201 are sequentially arranged at intervals from inside to outside around the rotation center, namely, the measuring ring 201 is close to the edge of the rotary disk 210, the incubation ring 203 is close to the center of the rotary disk 210, and the cleaning ring 202 is arranged between the incubation ring 203 and the measuring ring 201. In order to meet the requirements of incubation time of the analysis items, the number of incubation sites 213 is ensured without causing the size of the rotating disk 210 of the reaction device 200 to be too large, and the number of incubation circles 203 is at least two, for example, may be 2-10, wherein the incubation circle 203 closest to the rotation center is denoted as an inner incubation circle, and the incubation circle 203 farthest from the rotation center is denoted as an outer incubation circle. The number of the cleaning rings 202 is set to 1-2 according to the need of cleaning efficiency. The number of measuring rings 201 is 1, which can meet the measurement requirement.

The reaction apparatus 200 is provided with an incubation in and out station 15, a wash in station 16, a wash out station 17 and a measurement in and out station 18. In order that the reactor can enter and exit the respective incubation ring 203, cleaning ring 202 and measuring ring 201 of the reaction apparatus 200, the number of incubation in and out stations 15 is not less than the number of incubation rings 203, the number of cleaning in and out stations 16 and 17 is respectively equal to the number of cleaning rings 202, and the number of measuring in and out stations 18 is not less than the number of measuring rings 201, i.e. is at least one. Further, for the compactness of the overall layout, the movement stroke of the transfer assembly 220 is reduced and the reliability is improved, and the working efficiency is further improved, the cleaning and moving-in station 16 and the cleaning and moving-out station 17 are respectively arranged at two sides of the rotation center of the rotary disk 210, namely at two ends of the diameter of the cleaning ring 202, the incubation in-out station 15 is on the same side as the cleaning and moving-in station 16, and the measurement in-out station 18 is on the same side as the cleaning and moving-out station 17. The reactor thus removed from incubation access station 15 may be moved proximally from wash access station 16 to wash ring 202 and the reactor removed from wash removal station 17 may be moved proximally from measurement access station 18 to measurement ring 201.

Specifically, taking a one-step reaction mode of testing as an example, the transfer assembly 220 moves the reactor 20 on the mixing device 100 from the incubation in-out station 15 to the incubation site 213, and when the reactor 20 moves to the incubation in-out station 15 following the rotating disk 210, the transfer assembly 220 moves the reactor 20 out of the incubation site 213 from the incubation in-out station 15 and into the washing site 212 from the washing in-out station 16; when the reactor 20 moves to the cleaning and removing station 17 along with the rotating disc 210, the transferring component 220 moves the reactor 20 out of the cleaning and removing station 17 to the cleaning position 212 and into the signal reagent mixing unit 430 for signal reagent mixing, and then moves into the measuring position 211 from the measuring in-out station 18 after the mixing is completed; 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 sucking assembly 240 along with the rotating disc 210, the waste liquid sucking assembly 240 sucks all the waste liquid in the reactor 20, the reactor 20 after the waste liquid is sucked continues to move to the measuring in-out station 18 along with the rotating disc 210, at this time, the transferring assembly 220 moves the reactor 20 after the measurement is completed and the waste liquid is sucked out of the measuring station 211 at the measuring in-out station 18 and moves the reactor 20 into the discarding station. When performing other reaction mode tests, such as a time-lapse one-step or two-step test, transfer set 220 may move reactor 20 from incubation access station 15 out of incubation site 213, and reactor 20 from wash removal station 17 out of wash site 212 into mixing apparatus 100.

The movement path of the transfer assembly 220 between the initial station 13, the incubation access station 15, the wash access station 16, the wash access station 17, and the measurement access station 18 is a straight line that is projected in front of the rotating disk 210 through the center of rotation of the rotating disk 210. This may simplify the movement of the transfer set 220 and increase the efficiency of operation of the transfer set 220 to meet test throughput requirements. The straight line of the motion track of the transfer component 220 also passes through the signal reagent mixing unit 430, and the transfer component 220 can transfer the reactor 20 between the signal reagent mixing unit 430 and the measuring ring 201 and the cleaning ring 202.

To reduce the movement stroke of the individual transfer members 220, further improving the working efficiency and control accuracy, the number of transfer members 220 may be set to two, and a relay station 214 may be provided in 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 disk 210, the motion track of the other transfer assembly 220 forms a second projection on the rotating disk 210, and the first projection and the second projection are connected into the same straight line at the relay station 214 and are marked as a track straight line; a straight line passing through the relay 214 and perpendicular to the trajectory straight line is taken as a reference straight line. One of the transfer modules 220 is responsible for transferring the portion of the reactor 20 to the right of the reference line and the other transfer module 220 is responsible for transferring the portion of the reactor 20 to the left of the reference line. For example, in a two-step reaction mode test, transfer module 220 may be required to transfer reactor 20 from the left portion of the reference line to the right portion of the reference line when reactor 20 is moved from wash removal station 17 to wash station 212 and into mixing module 120 for filling with a second reagent, and reactor 20 may be transferred from wash station 212 to the left portion of the reference line to a relay station by one transfer module 220 and then transferred from the relay station to mixing module 120 to the right portion of the reference line by another transfer module 220.

In some embodiments, the relay station 214 is disposed at the center of rotation of the rotating disk 210 for compact layout and further to improve the efficiency of the coordinated engagement between the transfer units 220, thereby improving instrument throughput.

Referring to fig. 1 and 3, in the immunoassay analyzer 10, the transporting assembly 110, the mixing assembly 120, the sample pipetting unit 411 and the reagent pipetting unit 310 may be combined to form a diluting device, that is, the diluting device includes the transporting assembly 110, the mixing assembly 120 and the pipetting assembly, and the pipetting assembly includes the sample pipetting unit 411 and the reagent pipetting unit 310, where, of course, the structures and positions of the transporting assembly 110, the mixing assembly 120, the sample pipetting unit 411 and the reagent pipetting unit 310 may be kept unchanged. Similar to the above-described mixing device 100, the diluting device may be provided with the initial station 13, the first station 11, and the second station 12, and of course, the initial station 13 may be omitted.

The mixing assembly 120 is disposed on the transporting assembly 110, and the mixing assembly 120 is capable of simultaneously carrying at least two reactors 20, for example, two reactors 20, wherein one reactor 20 is denoted as a first reactor and the other reactor 20 is denoted as a second reactor. At least two receiving holes 122a are provided on the mixing assembly 120, and the first reactor and the second reactor can be placed in different receiving holes 122a, respectively. 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, when blending assembly 120 is at initial station 13, the first reactor is transferred from the supply tray into blending assembly 120 by transfer assembly 220; when the mixing assembly 120 moves to the first station 11, the sample is sucked up by the sample pipetting unit 411 and added to the first reactor; as the mixing assembly 120 moves to the second station 12, diluent is drawn into the first reactor by the reagent pipetting unit 310 and mixed with the sample to form a diluted sample; when the mixing assembly 120 returns to the initial station 13 again, the mixing assembly 120 is moved into the second reactor by the transfer assembly 220; transferring a portion of the diluted sample from the first reactor to the second reactor through the sample pipetting unit 411 when the mixing assembly 120 moves to the first station 11 again, aspirating a reagent component to the second reactor containing the diluted sample through the reagent pipetting unit 310 when the mixing assembly 120 moves to the second station 12 again, and mixing the diluted sample and the reagent component; when the mixing assembly 120 is finally moved to the initial station 13, the second reactor is moved into the incubation portion 213 of the reaction apparatus 200 by the transfer assembly 220. Of course, the first reactor may be moved to a disposal station for disposal. According to the above operation rule, the diluted sample and the reactor 20 in which the reagent components are uniformly mixed can be continuously output through the diluting device, so that the automatic dilution of the sample is realized.

Further, in order to greatly improve the efficiency of automatic sample dilution, the number of the mixing assemblies 120 is at least two, each mixing assembly 120 can realize automatic sample dilution, and the mixing assemblies 120 can realize automatic sample dilution in parallel or in series. Similar to the tandem mixing apparatus described above, the same transport assembly 110 synchronously drives the mixing assembly 120 to reciprocate cyclically between the first station 11 and the second station 12; similar to the parallel mixing apparatus described above, at least two transport assemblies 110 are provided, each transport assembly 110 having a mixing assembly 120 for carrying a reactor 20, each transport assembly 110 driving the mixing assembly 120 to reciprocate cyclically between the first station 11 and the second station 12.

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

s810, moving the mixing component 120 to the first station 11 with the first reactor, 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 and the diluent to form a diluted sample;

s840, transferring a second reactor onto the mixing assembly 120 and moving to the first station 11 again, and adding a part of the diluted sample in the first reactor 20 into the second reactor;

s850, moving the mixing assembly 120 to the second station 12, and adding the reagent component into the second reactor; a kind of electronic device with high-pressure air-conditioning system

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

When the number of mixing assemblies 120 is at least two, each mixing assembly 120 may be used in turn in the dilution step described above. Taking two mixing assemblies 120 as an example, a first mixing assembly is used for automatic dilution of a first sample, a second mixing assembly is used for dilution of a second sample, and a first mixing assembly … is used for automatic dilution of a third sample

To improve the efficiency of operation, both the diluent and the reagent components are placed on the same storage unit 320. When a portion of the diluted sample is added to the second reactor, the first reactor is removed from the mixing assembly 120 and discarded to a discarding station, although, for solid-liquid separation, the remaining diluted sample in the first reactor may be sucked first, and then the diluted sample is discarded from the first reactor formed after the complete suction.

To facilitate movement of the reactor 20 into and out of the mixing assembly 120, the mixing assembly 120 is cycled back and forth between the initial station 13, the first station 11, and the second station 12, with the first and second reactors 20 being moved into and out of the mixing assembly 120 at the initial station 13. Similarly, the initial station 13, the first station 11, and the second station 12 are arranged on the same line such that the initial station 13 is located between the first station 11 and the second station 12. For the sample and diluent in the first reactor 20, and the diluted sample and reagent in the second reactor 20, the mixing assembly 120 mixes them by means of non-contact eccentric oscillation.

It can be seen that the dilution device of the invention integrates the mixing component 120, can move between different stations, completes automatic dilution and mixing of samples, avoids dilution of a pipetting unit at one fixed station, transfers the reactor to another station for mixing, improves the efficiency and effect of dilution and mixing, and solves the problem of high throughput bottleneck of automatic dilution of samples for limiting immunoassay.

Referring to fig. 9, using the immunoassay device 10, an immunoassay method may be formed, and the immunoassay method mainly includes the following steps:

S910, at least two mixing assemblies 120 for carrying the reactor 20 are provided, such that the mixing assemblies 120 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 task executed by the blending component 120 can be circularly reproduced is denoted as a first period, that is, the smallest time interval in which the blending component 120 executes the same action twice consecutively is denoted as a first period, and the value obtained by dividing the first period by the number of the blending components 120 is denoted as a second period. From the first time of transferring one of the mixing assemblies 120 into the reactor 20, the time interval of one second period is sequentially staggered, and then each of the other mixing assemblies 120 is transferred into the reactor 20.

And S930, sequentially shifting the uniformly mixed reactors 20 out of the mixing assembly 120 by a time interval of one second period, and shifting a new reactor 20 on the mixing assembly 120 out of the reactor 20.

S940, the reactor 20, which is removed from the mixing assembly 120 and contains the reactants, is sequentially incubated, washed, separated and measured. The incubation time for the reactor 20 is 5-60 minutes.

It will be appreciated that this second period is equal to the time between consecutive outputs of two adjacent measured reactors 20 from the reaction device 200, i.e. the time between consecutive reports of two adjacent test results by the immunoassay meter 10.

When performing the reaction mode test of other methods, such as the time-lapse one-step method and the two-step method, in the above step S940, the incubated or washed reactor 20 may be transferred again to the mixing device 100 according to the steps S920 and S930, the second reagent is added and mixed uniformly, and after the mixing is completed, incubation, washing separation and measurement are performed according to the step S940.

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

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

And (3) second incubation, wherein the second reagent is added into the reactor 20 after the first incubation, and then the incubation is carried out 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 transferred to the mixing device 100 again according to the steps of S920 and S930, the second reagent is added and mixed, and after the mixing is completed, the second incubation, washing separation and measurement are performed according to the step S940.

The reagent is added to the reactor 20 in two portions, and the reactor 20 is uniformly mixed by the mixing device 100 after each addition of the reagent components. In some embodiments, the immunoassay method further comprises the steps of:

The reactor 20 after the first incubation is subjected to a first washing;

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

the reactor 20 after the second incubation is subjected to a second wash.

Specifically, after the reactor 20 is subjected to steps S910, S920, and S930, the reactor 20 is first incubated by the reaction device 200, then the reactor 20 after the first incubation is first cleaned by the reaction device 200, after the first cleaning, the reactor 20 is transferred to the mixing device 100 again according to steps S920 and S930, the second reagent is added and mixed uniformly, and after the mixing is completed, incubation, second cleaning and measurement are performed according to step S940.

In some embodiments, for example, the same transport assembly 110 drives all mixing assemblies 120 in synchronization, i.e., the sample and reagents in the reactor 20 are mixed using the series mixing method described above. For another example, the number of the transporting assemblies 110 is plural, and each transporting assembly 110 drives at least one mixing assembly 120 to move, that is, the sample and the reagent in the reactor 20 are mixed by the parallel mixing method.

With reference to the serial-type and parallel-type mixing methods, the transportation assembly 110 can drive the mixing assembly 120 to circularly reciprocate among the initial station 13, the first station 11 and the second station 12; at the initial station 13, the reactor 20 is moved into or out of the mixing assembly 120, a sample is added to the reactor 20 at the first station 11, and a reagent is added to the reactor 20 at the second station 12.

With reference to the structure and working principle of the reaction device 200, the reactor 20 can be incubated from the incubation in-out station 15 to the incubation position 213 on the rotating disk 210, the reactor 20 is moved from the cleaning in-out station 16 to the cleaning position 212 on the rotating disk 210 for cleaning and separation, the reactor 20 is moved from the cleaning out-out station 17 to the cleaning position 212 after the cleaning and separation are completed, and the reactor 20 is moved from the measuring in-out station 18 to the measuring position 211 on the rotating disk 210 for measurement; the movement tracks of the transfer assembly 220 between the incubation access station 15, the wash access station 16, the wash access station 17, and the measurement access station 18 are aligned.

A relay station 214 is disposed within an inner incubation ring (closest to a rotation center) of the rotating disk 210, and in particular, a relay station 214 for temporarily carrying the reactor 20 is disposed at the rotation center, and the number of transfer units 220 is set to two, wherein the movement locus of one transfer unit 220 forms a first projection at the rotating disk 210, and the movement locus of the other transfer unit 220 forms a second projection at the rotating disk 210, so that the first projection and the second projection are connected in a same line at the relay station 214. The incubation site 213, wash separation and measurement site 211 are arranged on the same rotating disc 210.

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

Referring to the above-described reagent sucking method, when the mixing assembly 120 is at the second station 12, reagent is sucked from the storage unit 320 to the reactor 20 by the reagent pipetting unit 310, and the reagent sucking includes 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 parts 321 of the storage units 320.

The storage portion 321 is moved along with the storage unit 320 so that the reagent pipetting unit 310 aspirates reagent in the reagent container arriving on the storage portion 321 of the pipetting station 14.

The shortest time window in which the sequence of actions or tasks performed by each memory unit 320 can be cyclically reproduced is equal to the first period, i.e. the smallest time interval in which the memory units 320 perform 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 towards the pipetting station 14, the other storage units 320 sequentially drive the reagent to move towards the corresponding pipetting station 14 by sequentially 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 for the immunoassay meter test throughput, the aspiration of the reagent includes the following sub-steps:

The action sequences of the plurality of storage units 320 are synchronized in series, i.e., the action sequences of the plurality of storage units 320 are synchronized in a working cycle during which each storage unit 320 can position the target storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent, but only one storage unit 320 is needed to position the target storage portion 321 to the pipetting station 14 for each working cycle for the reagent pipetting unit 310 to aspirate reagent. In any case, one of the storage units is caused to position the storage portion 321 to the pipetting station 14 for the reagent pipetting unit 310 to aspirate reagent for any one of the work cycles.

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

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

For a single reactor 20, taking one-step testing as an example, its workflow on the immunoassay analyzer 10 is as follows: first, empty and clean reactors 20 are placed on the mixing assembly 120 at the initial station 13 from the supply tray by transfer assembly 220; second, the transporting assembly 110 drives the mixing assembly 120 to move to the first station 11, and the sample pipetting unit 411 adds the sample into the reactor 20 located at the first station 11; third, the transporting assembly 110 drives the mixing assembly 120 to move to the second station 12, the reagent pipetting unit 310 adds reagent into the reactor 20 located at the second station 12, and the mixing assembly 120 mixes the sample and the reagent in the reactor 20; fourth, transfer assembly 220 moves the homogenized reactor 20 from the homogenizing assembly 120 through incubation access station 15 into incubation location 213 of rotating disk 210; fifth, after incubation, transfer assembly 220 removes reactor 20 from incubation site 213 at incubation access station 15 and transfers it from wash access station 16 to wash station 212 of carousel 210; sixthly, after the cleaning and separation are finished, adding a signal reagent into the reactor 20, removing the reactor 20 from the cleaning position 212 at the cleaning and removing station 17 by the transferring component 220, putting the reactor 20 into the signal reagent mixing unit 430 for mixing uniformly, transferring the reactor after the signal reagent mixing is finished to the measuring position 211 of the rotating disc 210 from the measuring and feeding station 18 by the transferring component 220, and measuring the optical signal in the reactor 20 by the measurer 230; sixth, waste liquid in the reaction after the measurement is completed is sucked up through the waste liquid sucking component 240; seventh, transfer assembly 220 removes reactor 20 from measurement access station 18, removes reactor 20 from rotating disk 210, and discards it to a discard station.

When the time-lapse one-step and two-step tests are performed, the transfer assembly 220 may transfer the incubated or washed reactor 20 again to the mixing assembly 120 of the mixing apparatus 100 to add the second reagent and mix, and after the mixing is completed, the transfer assembly 220 may transfer the uniformly mixed reactor 20 to the reaction apparatus 200 to perform incubation, washing separation and measurement.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims

1. A reaction apparatus, comprising:

A rotating disk for incubating, washing and measuring reactants in the reactor, the rotating disk having an incubation ring, a washing ring and a measuring ring disposed around a rotation center thereof;

a washing unit which is positioned above the rotating disk and can inject washing liquid into the reactor and extract unbound components, the washing unit comprising a signal-injecting reagent section for injecting a signal reagent into the reactor after washing separation;

the signal reagent mixing unit is used for mixing the signal reagent into the reactor after the signal reagent is added, and the signal reagent mixing unit is independent of the rotating disc;

The transfer component can transfer the reactor between the rotating disk and the signal reagent mixing unit, the movement track of the transfer component is positioned on the same straight line, and the straight line of the movement track of the transfer component passes through the signal reagent mixing unit; and

the waste liquid absorbing assembly is used for absorbing and removing signal reagents in the reactor after measurement is completed, and is connected to the liquid absorbing part of the cleaning assembly, can descend to the bottom in the reactor together with the liquid absorbing part of the cleaning assembly to absorb liquid, and is lifted off the reactor after absorption.

2. The reaction apparatus of claim 1, wherein the reactor containing the signal reagent is mixed by eccentric shaking.

3. The reaction apparatus of claim 1, wherein the signal reagent is mixed for a period of 2 to 6 seconds.

4. The reaction device according to claim 1, wherein the incubation ring is provided with incubation sites for incubating reactants in the reactor at intervals along its circumference, the washing ring is provided with washing sites for washing reactants in the reactor at intervals along its circumference, and the measuring ring is provided with measuring sites for measuring signals of reactants in the reactor at intervals along its circumference; the transfer component transfers the reaction container among the signal reagent mixing unit, the incubation position, the cleaning position and the measuring position.

5. The reaction apparatus of claim 4, wherein an incubation access station, a wash access station, and a measurement access station are provided; the incubation and access station is used for allowing the reactor to enter and exit the incubation position, the cleaning and moving-in station is used for allowing the reactor to move into the cleaning position, the cleaning and moving-out station is used for allowing the reactor to move out of the cleaning position, the measurement and access station is used for allowing the reactor to enter and exit the measurement position, and the transfer assembly moves among the incubation and access station, the cleaning and moving-in station, the cleaning and moving-out station and the measurement and access station.

6. The reaction apparatus of claim 5, wherein the transfer assembly moves the reactor containing the signal reagent from the incubation access station out of the wash station and into a signal reagent mixing unit.

7. The reaction apparatus of claim 5, wherein the transfer assembly moves the reactor after completion of the signal reagent mixing out of the signal reagent mixing unit and into the measurement site from the measurement in-out station.

8. The reaction device of claim 5, wherein the incubation ring, the washing ring, and the measuring ring are sequentially spaced around the rotation center from inside to outside.

9. The reaction device of claim 4, wherein the waste liquid absorbing assembly is located above a measuring ring of a rotating disk.

10. An immunoassay analyzer comprising the reaction device of any one of claims 1 to 9.