CN114518460A

CN114518460A - Sample analyzer and magnetic bead reagent mixing method

Info

Publication number: CN114518460A
Application number: CN202011303882.0A
Authority: CN
Inventors: 代剑东; 孙娟娟
Original assignee: Shenzhen Mindray Bio Medical Electronics Co Ltd
Current assignee: Shenzhen Mindray Bio Medical Electronics Co Ltd
Priority date: 2020-11-19
Filing date: 2020-11-19
Publication date: 2022-05-20

Abstract

A sample analyzer and a magnetic bead reagent blending method are provided, the sample analyzer comprises an ultrasonic device, a controller, a reagent bearing mechanism and a reagent dispensing mechanism; the controller is used for controlling the ultrasonic device to emit ultrasonic waves to the magnetic bead reagent which is not pretreated. Because the sample analyzer is equipped with ultrasonic device, ultrasonic device is arranged in launching the ultrasonic wave to the magnetic bead reagent not pretreated, and the ultrasonic wave can be with the homogeneous dispersion of the magnetic bead in the magnetic bead reagent not pretreated to subsequent reagent needle can absorb the even magnetic bead reagent of magnetic bead distribution, and then can guarantee the accuracy of detection. The ultrasonic device on the sample analyzer can perform ultrasonic mixing operation on the magnetic bead reagent which is not preprocessed, so that the magnetic bead reagent is not required to be preprocessed such as shaking before being operated on a computer, a doctor can directly operate the computer after taking the magnetic bead reagent, the operation of the doctor is facilitated, and the detection efficiency can be improved.

Description

Sample analyzer and magnetic bead reagent mixing method

Technical Field

The invention relates to in-vitro detection equipment, in particular to a sample analyzer and a magnetic bead reagent mixing method.

Background

An immunoassay analyzer is a high-sensitivity and high-specificity analyzer, and is often used for detecting various analysis indexes of blood, urine or other body fluids in clinical laboratories. Conventional immunoassays have many operating principles, including chemiluminescence, electrochemiluminescence, and the like. Taking a heterogeneous chemiluminescence immunoassay analyzer as an example, the main working principle is as follows: when a certain component in the sample needs to be measured, the corresponding antibody/antigen can be coated on the magnetic beads to form a magnetic bead reagent, and a specific marker is marked on the antibody to form a marking reagent. In the testing process, a sample to be tested, a magnetic bead reagent, a labeling reagent and other reagents are mixed together to form a reaction solution, the reaction solution is incubated under a certain condition to form a reaction complex, then the unbound labels and other reagents and sample components in the reaction system are removed through a magnetic separation technology, finally a substrate is added, the substrate reacts with the labels on the reaction complex to emit light, and then the detection result is obtained through photometric measurement.

The magnetic bead reagent in the immune luminescence analyzer is easy to generate a magnetic bead bottom sinking phenomenon under the condition of standing and storing, the density of the magnetic bead at the bottom is obviously greater than that of the magnetic bead at the upper layer, the magnetic bead and the reagent solution are in an uneven state, part of the magnetic bead reagent is sucked under the state to carry out immune detection, the density of the sucked magnetic bead is easily too large or too small, and then the test result deviates from a true value. In order to solve this problem, the conventional method is: the step of manual shaking is added before the magnetic bead reagents are loaded into the instrument. Although the added steps can achieve a certain mixing effect, additional pretreatment operation is required before the magnetic bead reagent is loaded on a machine, the testing efficiency of the whole machine is reduced, and the mixing effect of manual shaking is not ideal.

Disclosure of Invention

In one embodiment there is provided a sample analyzer comprising:

ultrasonic means for generating ultrasonic vibration to form ultrasonic waves;

a controller connected to the ultrasonic device, the controller being configured to control the ultrasonic device to emit ultrasonic waves into the non-pretreated magnetic bead reagent;

the reagent bearing mechanism is used for bearing a reagent container filled with a magnetic bead reagent; and

and the reagent dispensing mechanism is used for sucking the magnetic bead reagent subjected to ultrasonic operation from the reagent bearing mechanism and discharging the magnetic bead reagent subjected to ultrasonic operation into the containing cup.

In one embodiment, the non-pretreated magnetic bead reagent is a magnetic bead reagent that has not been subjected to any manual or automatic mixing prior to entering the sample analyzer.

In one embodiment, the non-pretreated magnetic bead reagent comprises a magnetic bead reagent with a lower magnetic bead density than an upper magnetic bead density of the reagent container.

In one embodiment, the reagent support mechanism is configured to support a reagent container containing an unpretreated magnetic bead reagent, and the ultrasonic device is configured to perform an ultrasonic operation on the unpretreated magnetic bead reagent on the reagent support mechanism.

In one embodiment, the sample analyzer further includes a reagent buffer mechanism for temporarily storing a reagent container containing an unpretreated magnetic bead reagent, the ultrasonic device is configured to perform an ultrasonic operation on the unpretreated magnetic bead reagent located on the reagent buffer mechanism, and the reagent transfer mechanism is configured to transfer the ultrasonically operated magnetic bead reagent on the reagent buffer mechanism to the reagent carrying mechanism.

In one embodiment, the controller is configured to acquire a test item parameter and perform an ultrasonic operation on the non-pretreated magnetic bead reagent by matching one ultrasonic mode from a plurality of preset ultrasonic modes according to the test item parameter.

In one embodiment, the plurality of ultrasound modes each have a different ultrasound intensity and/or ultrasound exposure time.

In one embodiment, the ultrasound device comprises an ultrasound transducer for generating ultrasound vibrations, a transmission member having a first end and a second end, the first end of the transmission member being connected to the ultrasound transducer, the second end of the transmission member having an outer diameter smaller than the inner diameter of the reagent container; the moving device is connected with the ultrasonic transducer, the moving device is used for driving the ultrasonic transducer and the transmission piece to move relative to the reagent container, and the second end of the transmission piece can be inserted into the non-pretreated magnetic bead reagent in the reagent container so as to transmit the ultrasonic vibration generated by the ultrasonic transducer to the non-pretreated magnetic bead reagent in the reagent container.

In one embodiment, the ultrasound device comprises an ultrasound transducer for generating ultrasound vibrations and a transmission member having a first end and a second end, the first end of the transmission member being connected to the ultrasound transducer; the second end of the transmission member is used for abutting against the outer wall of the reagent container, and the contact part of the outer wall of the reagent container and the transmission member is a part surrounding the non-pretreated magnetic bead reagent, so that the ultrasonic vibration generated by the ultrasonic transducer is transmitted to the non-pretreated magnetic bead reagent in the reagent container.

In one embodiment, the transmission member is a solid structure, and the outer diameter of the transmission member gradually decreases or is reduced in a stepped manner from the first end to the second end.

In one embodiment, the sample analyzer further comprises a sample carrying mechanism for carrying the sample, a sample dispensing mechanism for aspirating the sample from the sample carrying mechanism and discharging the sample into the receiving cup, a reaction mechanism for providing an incubation site for the reaction solution in the receiving cup, the reaction solution comprising the sample and the ultrasonically operated magnetic bead reagent, a magnetic separation mechanism for injecting a cleaning solution into the incubated reaction solution to perform a magnetic separation operation, and a measurement mechanism for optically measuring the reaction solution injected into the substrate.

In one embodiment, the ultrasonic device is further configured to perform an ultrasonic operation on at least one of the sample, the reaction solution to be incubated, the reaction solution after incubation, the reaction solution into which the cleaning solution is injected, and the reaction solution into which the substrate is injected.

An embodiment provides a method for uniformly mixing a magnetic bead reagent, which comprises the following steps:

loading a reagent container containing an untreated magnetic bead reagent onto a sample analyzer;

the ultrasonic device emits ultrasonic waves to the magnetic bead reagent which is not pretreated;

the reagent dispensing mechanism sucks the magnetic bead reagent subjected to the ultrasonic operation and injects the magnetic bead reagent subjected to the ultrasonic operation into the containing cup.

In one embodiment, the step of loading the reagent container containing the non-pretreated magnetic bead reagent onto the sample analyzer comprises: loading a reagent container containing magnetic bead reagents without pretreatment on a reagent bearing mechanism,

the method comprises the following steps that ultrasonic waves are transmitted to a magnetic bead reagent which is not pretreated by an ultrasonic device, and specifically comprises the following steps: the ultrasonic device performs ultrasonic operation on the magnetic bead reagent which is not preprocessed and is positioned on the reagent bearing mechanism.

In one embodiment, the step of loading the reagent container containing the non-pretreated magnetic bead reagent onto the sample analyzer is as follows: loading a reagent container containing magnetic bead reagents without pretreatment on a reagent caching mechanism;

the method comprises the following steps that ultrasonic waves are transmitted to a magnetic bead reagent which is not pretreated by an ultrasonic device, and specifically comprises the following steps: the ultrasonic device performs ultrasonic operation on the magnetic bead reagent which is not preprocessed and is positioned on the reagent caching mechanism,

the ultrasonic device emits ultrasonic waves to the magnetic bead reagent which is not pretreated, the reagent dispensing mechanism sucks the magnetic bead reagent which is operated by ultrasonic waves and injects the magnetic bead reagent which is operated by ultrasonic waves into the containing cup, and the method further comprises the following steps:

the reagent transferring mechanism transfers the reagent container containing the magnetic bead reagent which is operated by ultrasonic to the reagent bearing mechanism.

In one embodiment, the ultrasonic operation of the ultrasonic device is controlled by:

acquiring test item parameters;

and according to the test item parameters, matching one ultrasonic mode from a plurality of preset ultrasonic modes to perform ultrasonic operation on the bead reagent which is not preprocessed.

According to the sample analyzer and the magnetic bead reagent blending method of the embodiment, the sample analyzer is provided with the ultrasonic device, the ultrasonic device is used for transmitting ultrasonic waves to the non-pretreated magnetic bead reagent, and the ultrasonic waves can uniformly disperse magnetic beads in the non-pretreated magnetic bead reagent, so that a subsequent reagent needle can suck the magnetic bead reagent with uniformly distributed magnetic beads, and the detection accuracy can be further ensured. The ultrasonic device on the sample analyzer can perform ultrasonic mixing operation on the magnetic bead reagent which is not preprocessed, so that the magnetic bead reagent is not required to be preprocessed such as shaking before being operated on a computer, a doctor can directly operate the computer after taking the magnetic bead reagent, the operation of the doctor is facilitated, and the detection efficiency can be improved.

Drawings

FIG. 1 is a schematic diagram of an embodiment of an apparatus for analyzing an immune luminescence;

FIG. 2 is a block diagram showing the structure of a control section of an immunofluorescence analyzer in an embodiment;

FIG. 3 is a schematic diagram of the structure of a reagent support mechanism according to an embodiment;

FIG. 4 is a schematic diagram of the structure of a reagent support mechanism according to an embodiment;

FIG. 5 is a schematic diagram of the vortex mixer in one embodiment;

FIG. 6 is a schematic diagram of a contact ultrasonic apparatus according to an embodiment;

FIG. 7 is a structural view of a transmission member in one embodiment;

FIG. 8 is a structural view of a transmission member in one embodiment;

FIG. 9 is a diagram illustrating a mobile device according to an embodiment;

FIG. 10 is a schematic view of an ultrasonic apparatus in one embodiment;

FIG. 11 is a schematic diagram of a non-contact ultrasonic apparatus according to an embodiment;

FIG. 12 is a schematic diagram of a non-contact ultrasonic apparatus according to an embodiment;

FIG. 13 is a side view of a clasping means in an embodiment;

FIG. 14 is a top plan view of a clasping means in one embodiment;

FIG. 15 is a flowchart of a method for mixing a magnetic bead reagent according to an embodiment;

FIG. 16 is a timing diagram of a sample analysis method in accordance with one embodiment;

FIG. 17 is a flow chart of a method of sample analysis in one embodiment;

FIG. 18 is a flowchart of a method for mixing a magnetic bead reagent according to an embodiment;

FIG. 19 is a flow diagram of a method for sample analysis in one embodiment.

Detailed Description

The present invention will be described in further detail with reference to the following detailed description and accompanying drawings. Wherein like elements in different embodiments are numbered with like elements associated therewith. In the following description, numerous details are set forth in order to provide a better understanding of the present application. However, those skilled in the art will readily recognize that some of the features may be omitted or replaced with other elements, materials, methods in different instances. In some instances, operations related to the present application are not shown or described in the specification, so as not to obscure the core of the present application with excessive description, and it is not necessary for those skilled in the art to describe the related operations in detail, so that they can fully understand the related operations according to the description in the specification and the general knowledge in the art.

Furthermore, the features, operations, or characteristics described in the specification may be combined in any suitable manner to form various embodiments. Also, the various steps or actions in the method descriptions may be transposed or transposed in order, as will be apparent to one of ordinary skill in the art. Thus, the various sequences in the specification and drawings are for clarity of description of certain embodiments only and are not meant to be required unless otherwise indicated where a certain sequence must be followed.

The numbering of the components as such, e.g., "first", "second", etc., is used herein only to distinguish the objects as described, and does not have any sequential or technical meaning. The term "connected" and "coupled" when used in this application, unless otherwise indicated, includes both direct and indirect connections (couplings).

For an immune luminescence analyzer, the one-step test item in the invention means that one test item only needs one-step incubation; accordingly, a multi-step test item refers to a test item requiring multiple incubations, for example, a two-step test item refers to a test item requiring two incubations, where the reagents required for the first incubation are added to the sample, followed by the first incubation, and after the first incubation time is reached, the reagents required for the second incubation are added, followed by the second incubation, and after the second incubation time is reached, magnetic separation is performed again, and then the assay is performed. Generally, a multi-step test procedure requires magnetic separation after the final incubation step is completed before the assay can be performed; in a multi-step method test item, except the last step of incubation, whether magnetic separation is needed after other steps of incubation depends on the type of the test item and other factors. For example, a two-step test item may be referred to as a two-step two-separation test item if magnetic separation is required after incubation in the first step of the test, or as a two-step one-separation test item if magnetic separation is not required after incubation in the first step of the test.

In the one-step test item or the multi-step test item, the type of the reagent to be added in each step of incubation or each time of incubation can be one or more, which is determined according to the type of the test item and other factors; when there are a plurality of types of reagents to be added for incubation in a one-step test item or a multi-step test item, such a test item may be referred to as a multi-component test item.

In one embodiment, an ultrasonic device is arranged in the sample analyzer, and the non-pretreated magnetic bead reagent is ultrasonically and uniformly mixed through the ultrasonic device, so that the accuracy of item detection is improved. After the magnetic bead reagent is placed for a period of time, the magnetic beads sink to the bottom of the reagent container under the action of self weight, so that the density of the magnetic beads at the bottom of the reagent container is greater than that at the upper part of the reagent container. The non-pretreated magnetic bead reagent does not perform any treatment such as manual mixing or automatic mixing on the magnetic bead reagent before loading, and the magnetic beads of the non-pretreated magnetic bead reagent are generally in a non-uniformly distributed state.

Referring to fig. 1 and 2, the sample analyzer may be a biochemical analyzer or an immunoassay analyzer, and the immunoassay analyzer mainly includes an ultrasonic device 10, a sample carrying mechanism 21, a sample dispensing mechanism 22, a reagent carrying mechanism 31, a reagent dispensing mechanism 32, a reaction mechanism 40, a magnetic separation mechanism 50, and a controller 60. The sample support mechanism 21, the sample dispensing mechanism 22, the reagent support mechanism 31, the reagent dispensing mechanism 32, the reaction mechanism 40, the magnetic separation mechanism 50, and the ultrasonic apparatus 10 are all mounted on the base 100, the controller 60 is mounted on the main body of the base 100, and the controller 60 may also be mounted on the base 100. The biochemical analyzer does not include the magnetic separation mechanism described above.

The immune luminescence analyzer further comprises a cup loading mechanism 71, a cup throwing position 72, a first transfer mechanism 81, a second transfer mechanism 82 and a measuring mechanism 90 which are arranged on the base 100.

Wherein, the reaction mechanism 40 is arranged in the middle, and the reagent bearing mechanism 31, the magnetic separation mechanism 50, the ultrasonic device 10, the cup feeding mechanism 71, the cup throwing position 72 and the measuring mechanism 90 are respectively arranged around the reaction mechanism 40.

The cup loading mechanism 71 is used for storing a new used receiving cup 103, and the receiving cup 103 is also called a reaction cup. The cup loading mechanism 71 itself also has a cup moving function, and can move the storage cup 103 from the storage position to a position to be gripped.

The first transfer mechanism 81 is a cup grasping mechanism, and the first transfer mechanism 81 is used for transferring a new receiving cup 103 on the cup loading mechanism 71 to the sample loading position 101 near the reaction mechanism 40 and transferring the receiving cup 103 on the sample loading position 101 to the reaction mechanism 40.

The cup throwing position 72 is arranged close to the first transfer mechanism 81, and the cup throwing position 72 is used for recycling the used accommodating cup 103. The first transfer mechanism 81 is also used for transferring the detected containing cup 103 on the reaction mechanism 40 to the cup throwing position 72.

The sample support mechanism 21 is used for supporting a sample. The Sample support mechanism 21 may include, in some examples, a Sample Delivery Module (SDM); in other examples, the sample carrier mechanism 21 may be a sample tray including a plurality of sample sites for placing samples, such as sample tubes, and the sample tray may be configured to rotate to dispatch the samples to corresponding locations, such as locations for the sample dispensing mechanism 22 to aspirate the samples.

The sample dispensing mechanism 22 includes a sampling needle, a moving mechanism for driving the sampling needle to move between the sample carrying mechanism 21 and the sample application site 101, and a drive pump for providing the sampling needle with power for sucking and discharging samples. The sample dispensing mechanism 22 is used for sucking the sample in the sample tube on the sample carrying mechanism 21 and for dispensing the sucked sample into the receiving cup 103 on the dispensing position 101.

The reaction mechanism 40 is used for providing an incubation place for the reaction solution, the reaction mechanism 40 can be a reaction disc which is arranged in a disc-shaped structure and provided with one or more placing positions for placing reaction cups, and the reaction disc can rotate and drive the reaction cups in the placing positions to rotate and is used for scheduling the reaction cups in the reaction disc and incubating the reaction solution in the reaction cups.

The magnetic separation mechanism 50 comprises a cleaning solution dispensing structure, a magnetic absorption structure, a liquid absorption structure and a substrate dispensing structure, wherein the cleaning solution dispensing structure is used for dispensing a cleaning solution into the incubated reaction solution, and the cleaning solution is used for separating free substances in the incubated reaction solution; the magnetic attraction structure is used for performing magnetic attraction operation on the reaction liquid filled with the cleaning liquid, and is used for adsorbing a reaction compound combined with the magnetic beads; the liquid-absorbing structure is used for discharging the components other than the reaction complex bound to the magnetic beads out of the receiving cup 103; the substrate dispensing mechanism is used to dispense a substrate into the reaction solution in the receiving cup 103, and the substrate reacts with the reaction complex in the reaction solution, and the substrate labels the reaction complex by light emission.

The number of the magnetic separation mechanisms 50 is two, and the two magnetic separation mechanisms 50 can work independently of each other to improve the testing efficiency.

A mixing position 102 is provided at a position close to the reaction mechanism 40 and the magnetic separation mechanism 50, a cup holder for placing the holding cup 103 is provided at the mixing position 102 and the sample addition position 101, and the second transfer mechanism 82 is used for transferring the holding cup 103 among the reaction mechanism 40, the magnetic separation mechanism 50 and the mixing position 102.

The measurement means 90 is used to perform optical measurement on the reaction solution after completion of incubation, and obtain reaction data of the sample. For example, the measuring unit 90 detects the light emission intensity of the reaction solution to be measured, and calculates the concentration of the component to be measured in the sample from the calibration curve.

The base 100 is further provided with a cleaning mechanism and a waste liquid suction mechanism, the cleaning mechanism is used for cleaning the sampling needle and the reagent needle, and the waste liquid suction mechanism is used for sucking reaction liquid after detection.

Referring to fig. 1 and 3, the reagent carrying mechanism 31 is used for carrying the magnetic bead reagent without pretreatment. In one embodiment, the reagent carrying mechanism 31 may be a reagent disk, the reagent disk is configured in a disk-shaped structure and has a plurality of positions for carrying reagent containers, and the reagent carrying mechanism 31 can rotate and drive the reagent containers carried by the reagent carrying mechanism 31 to rotate to a specific position, for example, a position for sucking reagent by the reagent dispensing mechanism 32. The number of the reagent carrying mechanism 31 may be one or more.

The ultrasonic device 10 is disposed near the reagent carrying mechanism 31, the ultrasonic device 10 is configured to perform an ultrasonic blending operation on the non-pretreated magnetic bead reagent in the reagent container 105 on the reagent carrying mechanism 31, the ultrasonic device 10 is configured to transmit an ultrasonic wave to the non-pretreated magnetic bead reagent in the reagent container 105, and the ultrasonic wave uniformly disperses the magnetic beads in the non-pretreated magnetic bead reagent, so that the magnetic beads in the magnetic bead reagent are uniformly distributed in the reagent container 105.

The reagent dispensing mechanism 32 includes a reagent needle, a moving mechanism for driving the reagent needle to move between the reagent carrying mechanism 31 and the reaction mechanism 40, and a drive pump for supplying power to the reagent needle for sucking and discharging a reagent. The reagent dispensing mechanism 32 is used for sucking the non-pretreated magnetic bead reagent in the reagent tube of the reagent bearing mechanism 31, and for filling the sucked non-pretreated magnetic bead reagent into the containing cup 103 with the sample on the reaction mechanism 40, and the sample and the reagent in the containing cup 103 are mixed and reacted to form a reaction solution.

Referring to fig. 4, in an embodiment, a reagent buffer mechanism 33 and a reagent transferring mechanism 34 are further disposed on the rack 100, the reagent buffer mechanism 33 is disposed near the reagent carrying mechanism 31, and a plurality of placing positions are disposed in the reagent buffer mechanism 33, and the placing positions are used for carrying the reagent containers 105 containing the non-pretreated magnetic bead reagents. When the flux of the magnetic bead reagent on the machine is greater than the consumed flux of the magnetic bead reagent on the reagent bearing mechanism 31, the reagent buffer mechanism 33 is used for buffering excessive reagent containers 105 containing the magnetic bead reagent which is not preprocessed, so that the reagent separate-injection mechanism 32 can be ensured to continuously and uninterruptedly fill the magnetic bead reagent, and the detection efficiency is improved.

The reagent transfer mechanism 34 has the same or similar structure as the first transfer mechanism 81 and the second transfer mechanism 82, the reagent transfer mechanism 34 is installed between the reagent buffer mechanism 33 and the reagent support mechanism 31, and the reagent transfer mechanism 34 is used for transferring the reagent container 10 containing the non-pretreated magnetic bead reagent on the reagent buffer mechanism 33 into the reagent support mechanism 31.

The ultrasonic device 10 is disposed near the reagent buffer mechanism 33, the ultrasonic device 10 is configured to perform an ultrasonic blending operation on the non-pretreated magnetic bead reagent in the reagent container 105 on the reagent buffer mechanism 33, the ultrasonic device 10 is configured to transmit an ultrasonic wave to the non-pretreated magnetic bead reagent in the reagent container 105, and the ultrasonic wave uniformly disperses the magnetic beads in the non-pretreated magnetic bead reagent, so that the magnetic beads in the non-pretreated magnetic bead reagent are uniformly distributed in the reagent container 105.

In one embodiment, the ultrasonic apparatus 10 is provided with a plurality of ultrasonic apparatuses, wherein one ultrasonic apparatus 10 is disposed near the mixing position 102, the second transfer mechanism 82 is configured to transfer the containing cup 103 containing the reaction solution to be incubated from the reaction mechanism 40 to the mixing position 102, and the ultrasonic apparatus 10 is configured to perform an ultrasonic mixing operation on the reaction solution at the mixing position 102.

The second transfer mechanism 82 is further configured to transfer the cup 103 containing the incubated reaction solution from the reaction mechanism 40 to the mixing position 102, and the ultrasonic apparatus 10 is further configured to perform an ultrasonic mixing operation on the reaction solution incubated on the mixing position 102.

The second transfer mechanism 82 is also used for transferring the reaction liquid containing cup 103 filled with the injected substrate from the magnetic separation mechanism 50 to the mixing position 102, and the ultrasonic device 10 is also used for performing ultrasonic mixing operation on the reaction liquid filled with the substrate at the mixing position 102.

In one embodiment, the ultrasonic device 10 is provided with a plurality of ultrasonic devices, one of the ultrasonic devices 10 is disposed near the sample loading site 101, and the ultrasonic device 10 is configured to perform an ultrasonic mixing operation on the sample loaded on the sample loading site 101.

In one embodiment, the ultrasonic device 10 is provided with a plurality of ultrasonic devices 10, wherein one ultrasonic device 10 is arranged near the magnetic separation mechanism 50, or one ultrasonic device 10 is installed in the magnetic separation mechanism 50, and the ultrasonic device 10 is used for performing an ultrasonic blending operation on the reaction liquid injected with the cleaning liquid in the magnetic separation mechanism 50.

In one embodiment, at least two mixing positions 102 are provided, the placing positions of the containing cups 103 are increased, one ultrasonic device 10 corresponds to at least two mixing positions 102, that is, one ultrasonic device 10 can perform ultrasonic mixing on reaction liquids 104 in a plurality of containing cups 103 respectively, one containing cup 103 can perform transfer or other operations during ultrasonic mixing, the containing cups 103 on other mixing positions 102 can perform transfer or other operations, and the containing cups 103 on a plurality of mixing positions 102 realize alternate mixing, so as to improve the detection efficiency.

In one embodiment, the ultrasonic devices 10 may also be disposed in a one-to-one correspondence with the blending locations 102.

Referring to fig. 5, in an embodiment, a vortex mixing device 200 is further installed at the mixing position 102, the vortex mixing device 200 includes a driving motor 201, a transmission belt 202, an eccentric rotating shaft 203, a mounting base 204, and the like, the driving motor 201 is fixedly installed on the mounting base 204, an output shaft of the driving motor 201 is downward disposed, the eccentric rotating shaft 203 is rotatably installed on the mounting base 204 through a bearing, the eccentric rotating shaft 203 is vertically disposed, the eccentric rotating shaft 203 has a first section and a second section that are not collinear, the first section is located at a lower position, the second section is located at an upper position, and the first section and the second section of the eccentric rotating shaft 203 are both parallel to the output shaft of the driving motor 201. Install the band pulley respectively on the output shaft of driving motor 201 and the first section of eccentric pivot 203, drive belt 202 is connected on the band pulley of driving motor 201 and eccentric pivot 203, driving motor 201 passes through the eccentric pivot 203 of drive belt 202 drive and rotates, install on the eccentric pivot 203 and be used for placing the cup holder 205 that holds cup 103, and then eccentric pivot 203 can drive the cup 103 eccentric rotation that holds that is located on the cup holder 205, carry out the swirl mixing operation to the reaction liquid that holds in the cup 103. The driving motor 201 is connected with the controller 60, and the controller 60 controls the output power and the output duration of the driving motor 201 so as to realize multiple vortex mixing modes with different intensities and time.

In the present embodiment, the controller 60 is connected to the ultrasonic apparatus 10, the sample dispensing mechanism 22, the reagent dispensing mechanism 32, the reaction mechanism 40, the magnetic separation mechanism 50, the first transfer mechanism 81, and the second transfer mechanism 82, respectively, and the controller 60 is configured to control the test timing of the entire sample analyzer.

When the controller 60 controls the ultrasonic apparatus 10, the controller 60 obtains a test item input or selected by a doctor, obtains a test item parameter corresponding to the test item, and matches one ultrasonic mode from a plurality of ultrasonic modes according to the test item parameter to perform an ultrasonic mixing operation on the non-pretreated magnetic bead reagent.

Different ultrasonic modes respectively have different ultrasonic blending intensities or different ultrasonic blending times, wherein the blending intensity is controlled by input power, at least three ultrasonic blending intensities including intensity, intensity and intensity can be set, and at least two ultrasonic blending times including 1s and 2s can be set.

The ultrasonic blending mode at least comprises the following steps:

in the first blending mode, an ultrasonic blending operation is performed by adopting an ultrasonic device 10, the ultrasonic blending intensity is medium, and the ultrasonic blending time is 1 s;

in the second blending mode, an ultrasonic blending operation is executed by adopting an ultrasonic device 10, the ultrasonic blending intensity is weak, and the ultrasonic blending time is 2 s;

in the third blending mode, the ultrasonic blending operation is performed by the ultrasonic device 10, the ultrasonic blending intensity is strong, and the ultrasonic blending time is 1 s.

The test item parameters include numbers, letters, or a combination thereof, etc., such as the test item parameter of the TNI (troponin) item of 2, and the test item parameter of the E2 (estradiol) item of 0 and 1. The controller 60 is pre-stored with project test parameters corresponding to different test projects, each corresponding to a blending mode. If the test item parameter 0 corresponds to the first blending mode, when the test item parameter acquired by the controller 60 is 0, driving the ultrasonic device 10 to perform ultrasonic blending with the intensity of the non-pretreated magnetic bead reagent and the time of 1 s; the test item parameter 1 corresponds to the second blending mode, and when the test item parameter acquired by the controller 60 is 1, the ultrasonic device 10 is driven to perform ultrasonic blending with weak intensity and 2 seconds on the non-pretreated magnetic bead reagent; the test item parameter 2 corresponds to the third blending mode, and when the test item parameter acquired by the controller 60 is operation 2, the ultrasonic device 10 is driven to perform ultrasonic blending with strong intensity and 1s of time on the non-pretreated magnetic bead reagent.

Different ultrasonic blending modes can be set according to specific test items, so that the ultrasonic device 10 can perform effective ultrasonic blending on the non-pretreated magnetic bead reagent in different test items.

Referring to fig. 6, in the present embodiment, the ultrasonic apparatus 10 is a device independent from other mechanisms, that is, the ultrasonic apparatus 10 can operate independently, for example, the ultrasonic apparatus 10 can operate independently from the sample dispensing mechanism 22, and the ultrasonic apparatus 10 can operate synchronously or asynchronously with other mechanisms, so as to improve the efficiency of item detection.

The ultrasonic device 10 is a contact type ultrasonic device, the ultrasonic device 10 comprises an ultrasonic transducer 11, a transmission piece 12 and a moving device 13, the ultrasonic transducer 11 comprises a back lining layer, a piezoelectric layer and a matching layer which are sequentially connected, the piezoelectric layer is a piezoelectric crystal, the piezoelectric crystal generates compression and expansion in the thickness direction through inverse piezoelectric effect under the action of a driving electric signal, and the frequency of the deformation reaches ultrasonic frequency to form ultrasonic vibration.

Referring to fig. 6 and 7, the transmission member 12 is a solid rod-shaped structure, the transmission member 12 has a first end and a second end, the first end is an upper end, the second end is a lower end, the first end of the transmission member 12 is provided with an external thread, the lower end of the ultrasonic transducer 11 is provided with an internal thread, the transmission member 12 is installed at the lower end of the ultrasonic transducer 11 in a threaded connection manner, and the transmission member 12 can also be connected with the ultrasonic transducer 11 in other manners such as clamping. The transmission member 12 is a resonant rod, the transmission member 12 is connected to the matching layer of the ultrasonic transducer 11, and the transmission member 12 transmits the ultrasonic vibration. Compared with the transmission member 12 with a hollow structure, the solid transmission member 12 is beneficial to the transmission of axial vibration, and when the outer diameter of the transmission member 12 is reduced along the transmission direction of ultrasonic vibration, the solid transmission member 12 is beneficial to the convergence of energy so as to realize better ultrasonic uniform mixing effect.

The external diameter of the transmission part 12 is gradually reduced or reduced in a step mode from the first end to the second end, the transmission part 12 has the function of energy gathering, when the ultrasonic vibration is transmitted from the first end to the second end, the axial cross-sectional area of the second end relative to the first end is reduced, the ultrasonic vibration is gathered more at the second end relative to the first end, the amplitude of the emergent ultrasonic vibration is enlarged by the second end of the transmission part 12 relative to the first end, and therefore the emergent ultrasonic energy is improved.

Specifically, the transmission member 12 includes a first end 121, an intermediate section 122, and a second end 123, wherein the first end 121 is an externally threaded connecting end, the second end 123 is a needle bar structure, and the second end 123 has an outer diameter smaller than the inner diameter of the receiving cup 103, such that the second end 123 of the transmission member 12 can be inserted into the receiving cup 103. Middle section 122 is loudspeaker column structure, and the one end that middle section 122 and first end 121 are connected is the loudspeaker main aspects, and the one end that middle section 122 and second end 123 are connected is the loudspeaker tip, and the diameter of axle that middle section 122 followed the loudspeaker main aspects to the loudspeaker tip reduces gradually.

The intermediate section 122 may also be comprised of one or any combination of cylindrical and conical rods. Referring to FIG. 8, the middle section 122 of the a-structure includes two cylindrical rods with different diameters; the middle section 122 of the b-structure comprises four cylindrical rods with different diameters; the middle section 122 of the c-configuration comprises a section of conical rod; the intermediate section 122 of the d-configuration comprises two cylindrical rods of different diameters and one conical rod. The five structures of the transmission member 12 are all structures that gradually decrease or step-wise decrease from the first end to the second end, and can play a role in amplifying the amplitude.

Referring to fig. 9, the moving device 13 includes a mounting seat 131, a swing arm assembly 132, a first moving assembly 133 and a second moving assembly 134.

The swing arm assembly 132 comprises a swing arm 1321 and a lifting rod 1322, the lifting rod 1322 can be vertically lifted and can be rotatably installed on the installation seat 131, the swing arm 1321 is horizontally arranged, one end of the swing arm 1321 is connected to the lifting rod 1322, and the ultrasonic transducer 11 is installed at one end, far away from the lifting rod 1322, of the swing arm 1321. The swing arm assembly 132 is used for driving the ultrasonic transducer 11 and the transmission member 12 to vertically lift and horizontally rotate. In one embodiment, the swing arm 1321 and the lift pin 1322 may also be a unitary structure.

The first moving assembly 133 is a lifting assembly, the first moving assembly 133 includes a lifting motor 1331 and a lifting transmission assembly 1332, the lifting motor 1331 is installed on the installation base 131, the lifting transmission assembly 1332 includes a transmission wheel, a transmission belt, a gear and a rack, the rack is vertically installed on the lifting rod 1322, the gear is rotatably installed on the installation base 131, the gear is engaged with the rack, the lifting motor 1331 is connected with the gear through the transmission wheel and the transmission belt, and the lifting motor 1331 drives the lifting rod 1322 to move up and down through the rack and pinion. In one embodiment, the first moving assembly 133 is a linear motor, and an output shaft of the linear motor is directly connected to the lifting rod 1322, and is also capable of driving the lifting rod 1322 to move up and down.

Second removes subassembly 134 and is the runner assembly, second removes subassembly 134 includes rotation motor 1341 and rotation transmission subassembly 1342, rotation motor 1341 installs on mount pad 131, rotation transmission subassembly 1342 includes drive belt and bull gear, the drive belt is the gear belt, the bull gear suit is on lifter 1322, the bull gear passes through the key-type connection with lifter 1322, lifter 1322 can be relative to bull gear elevating movement, the bull gear is used for driving lifter 1322 to rotate, rotation motor 1341 passes through the drive belt and is connected with the bull gear, rotation motor 1341 is used for driving lifter 1322 to rotate. In one embodiment, the rotation motor 1341 is coupled to the lift rod 1322 via a gear set, and is also capable of driving the lift rod 1322 to rotate.

In one embodiment, the moving device 13 only includes the mounting seat 131, the swing arm assembly 132 and the first moving assembly 133, the ultrasonic device 10 has a lifting function, and the ultrasonic device 10 is used for performing a blending operation on the reaction liquid 104 in the containing cup 103 at a specific blending position 102.

In one embodiment, the second moving assembly 134 may also be a planar moving assembly formed by combining X-axis movement and Y-axis movement, which are respectively realized by two motors, and can also realize the driving of the transferring member 12 to move alternately between the blending positions 102.

Referring to fig. 10, in the present embodiment, the transmission member 12 of the ultrasonic apparatus 10 is directly inserted into the reaction liquid 104 of the containing cup 103. The ultrasonic device 10 has a predetermined frequency and voltage so that the ultrasonic vibration propagates mainly in the axial direction, and the second end surface of the transmission member 12 is an ultrasonic wave emitting surface. During ultrasonic mixing, the second end face of the transmission member 12 emits ultrasonic waves into the reaction liquid 104, an ultrasonic sound field is formed in the reaction liquid 104, and the reaction liquid 104 can form violent liquid flow under the action of the ultrasonic sound field, so that the components in the reaction liquid 104 are mixed uniformly.

In addition to the vibration effect of the ultrasonic wave, the reaction liquid 104 can be uniformly mixed, and the cavitation effect generated by the ultrasonic wave in the liquid can also uniformly disperse some agglomerated and bonded substances in the reaction liquid 104. When the frequency and the sound pressure of the ultrasonic waves are controlled and the amplification effect of the transmission member 12 is combined, the ultrasonic energy entering the reaction liquid 104 of the containing cup 103 is greater than the threshold value of the ultrasonic cavitation, and the ultrasonic cavitation phenomenon can be generated in the reaction liquid 104 in the ultrasonic uniform mixing process. When ultrasonic cavitation occurs, a large amount of energy is released, certain acting force is generated on some agglomerated and adhered substances in the reaction liquid 104, so that the agglomerated and adhered substances are dispersed, and meanwhile, the substances can be uniformly dispersed in the reaction cup under the action of ultrasonic vibration and uniform mixing.

In one embodiment, the ultrasonic device 10 is a non-contact ultrasonic mixing device, the ultrasonic device 10 is in contact with the containing cup 103, and the ultrasonic waves emitted by the ultrasonic device 10 are transmitted to the reaction liquid in the containing cup 103 through the containing cup 103.

Referring to fig. 11 and 12, the ultrasonic apparatus 10 includes an ultrasonic transducer 11 and a transmission member 12. When the ultrasonic mixing is performed, the second end of the transmission member 12 abuts against the outer wall of the containing cup 103, and the ultrasonic vibration is transmitted to the reaction solution 104 through the containing cup 103. Since the transmission element 12 does not need to be inserted into the receiving cup 103, the axial length of the transmission element 12 is shorter than that of a contact transmission element, but it also has the characteristic of gradually or stepwise decreasing from the first end to the second end to achieve an amplification of the amplitude.

When the ultrasonic mixing is performed, the second end face of the transmission member 12 of the present embodiment abuts against the outer wall of the containing cup 103, and the portion of the outer wall of the containing cup 103, which is in contact with the transmission member 12, is a portion surrounding the reaction liquid 104, so as to transmit the ultrasonic vibration generated by the ultrasonic transducer 11 to the liquid in the containing cup 103. The portion of the receiving cup 103 surrounding the reaction solution 104 is the bottom of the receiving cup 103 and the lower end side wall connected to the bottom, so that the second end of the transmission member 12 abuts against the bottom of the receiving cup 103 and any position of the lower end side wall connected to the bottom, and the ultrasonic vibration can be transmitted to the liquid in the receiving cup 103.

In this embodiment, the ultrasonic apparatus 10 is a movable structure, the ultrasonic apparatus 10 further includes a moving device, the moving device includes a mounting seat and a horizontal moving component, the horizontal moving component is mounted on the mounting seat, the ultrasonic transducer is mounted on the horizontal moving component, the horizontal moving component is an air cylinder or a linear motor, and the horizontal moving component is used for driving the second end of the transmission member 12 to abut against or leave the outer wall of the accommodating cup 103 on the blending position 102.

In one embodiment, the ultrasonic device 10 is configured as a fixed structure, and the delivery member 12 is located at a predetermined position, such that after the receiving cup 103 is placed at the blending position 102, the receiving cup 103 will directly contact the second end of the delivery member 12.

In this embodiment, the sample analyzer further includes a holding device 110, and the holding device 110 is used to limit the radial degree of freedom of the containing cup 103 on the blending position 102.

Referring to fig. 13 and 14, the clasping device 110 includes two oppositely disposed clamping assemblies, each clamping assembly includes a clasping motor 111, a clasping cam 112 and a clasping clamping block 113, the clasping motor 111 is mounted on the base 100, an output shaft of the clasping motor 111 is vertically disposed upward, the output shaft of the clasping motor 111 is in transmission connection with the clasping cam 112, the clasping cam 112 is horizontally disposed, the clasping cam 112 is in contact connection with the clasping clamping block 113, the clasping clamping block 113 is horizontally movably mounted on the base 100, and two side surfaces of the clasping clamping block 113 are respectively adapted to the accommodating cup 103 and the clasping cam 112. If the accommodating cup 103 is a circular tube, the surface of the holding clamp block 113 facing the accommodating cup 103 is an inward concave arc surface; if the receiving cup 103 is a square tube, the surface of the clasping clamp block 113 facing the receiving cup 103 is a plane. The convex part of the leading and clasping cam 112 is a convex arc surface, and the clasping clamping block 113 is a concave arc surface with larger curvature towards the clasping cam 112 surface, so that the concave arc surface of the clasping clamping block 113 can guide the convex part of the clasping cam 112 to slide in and slide out. Embrace motor 111 and be used for the drive to embrace cam 112 and rotate to it holds the cup 103 to make to embrace cam 112 and drive and embrace clamp splice 113 and be close to or keep away from, when two bellying of embracing cam 112 all towards holding cup 103 and align on the same line, two embrace clamp splice 113 and will hold cup 103 and embrace, the radial degree of freedom that holds cup 103 is restricted, and then can avoid holding rocking of cup 103 at the supersound mixing in-process, guarantee to hold the good contact between cup 103 and the transmission 12.

In this embodiment, since the ultrasonic device 10 is in contact with the lower end of the containing cup 103 to achieve ultrasonic uniform mixing, the clasping clamping block 113 of the clasping device 110 clasps the side wall of the lower end of the containing cup 103, so as to improve the stability of clasping. When the transmission member 12 of the ultrasonic apparatus 10 abuts against the lower end side wall of the receiving cup 103, the transmission member 12 and the clasping block 113 are arranged to be offset from each other on the lower end side wall of the receiving cup 103.

In an embodiment, the clasping device 110 may also include a linear driving element and a clasping clamping block, the linear driving element is an air cylinder or a linear motor, and the linear driving element drives the clasping clamping block to approach and leave the accommodating cup 103, so that the accommodating cup 103 can be limited.

The non-contact ultrasonic device 10 is also used in the present embodiment, and can transmit ultrasonic vibration to the reaction liquid 104 in the containing cup 103 to form an ultrasonic sound field and an ultrasonic cavitation phenomenon, so as to ultrasonically mix the reaction liquid 104 in the containing cup 103.

In one embodiment, the ultrasound device 10 and the reagent dispensing mechanism 32 are connected as an integral structure. The ultrasonic apparatus 10 includes an ultrasonic transducer, the ultrasonic transducer is disposed on the moving mechanism of the reagent dispensing mechanism 32, the ultrasonic transducer is connected to the reagent needle, the ultrasonic vibration generated by the ultrasonic transducer is transmitted to the reagent needle, and the reagent needle transmits the ultrasonic wave to the magnetic bead reagent which is not pretreated. When the ultrasonic apparatus 10 and the reagent dispensing mechanism 32 are combined, the reagent needle can be used to perform an ultrasonic mixing operation on the non-pretreated magnetic bead reagent in addition to the reagent needle that can suck the non-pretreated magnetic bead reagent. Specifically, the reagent needle can perform an ultrasonic mixing operation on the non-pretreated magnetic bead reagent in the reagent container on the reagent carrying mechanism 31 or the reagent buffer mechanism 33.

In one embodiment, a method for uniformly mixing a magnetic bead reagent is provided, and the sample analysis method is performed by the sample analyzer in the above embodiment.

Referring to fig. 14, the method for mixing a magnetic bead reagent of the present embodiment includes the following steps:

s101: a magnetic bead reagent is put on the machine;

the doctor places the reagent vessel 105 containing the non-pretreated magnetic bead reagent into the reagent support mechanism 31. After the magnetic bead reagent is stood for a period of time, the magnetic beads sink to the bottom of the reagent container under the action of self weight, so that the density of the magnetic beads at the bottom of the reagent container is greater than that at the upper part of the reagent container. The bead reagent which is not pretreated does not carry out any treatment such as manual mixing or automatic mixing and the like on the bead reagent before the bead reagent is loaded, and the bead reagent which is not pretreated is generally in a state that beads are not uniformly distributed.

S102: ultrasonically mixing uniformly;

the ultrasonic device 10 emits ultrasonic waves into the non-pretreated magnetic bead reagent on the reagent carrying mechanism 31, and performs an ultrasonic mixing operation on the non-pretreated magnetic bead reagent. The ultrasonic device 10 uniformly disperses the magnetic beads in the non-pretreated magnetic bead reagent, so that the subsequent reagent dispensing mechanism 32 can suck the magnetic bead reagent with uniformly distributed magnetic beads.

The ultrasonic blending mode at least comprises the following steps:

S103: adding a reagent;

the first transfer mechanism 81 transfers the cup 103 containing the sample S from the sample addition site 101 to the outer ring in the reaction mechanism 40; the reaction mechanism 40 transfers the containing cup 103 needing to be added with the reagent R to a reagent adding position;

the reagent dispensing mechanism 32 sucks the magnetic bead reagent R after the ultrasound from the reagent holding mechanism 31, and dispenses the magnetic bead reagent R after the ultrasound sucked into the receiving cup 103 at the sample addition reagent position in the reaction mechanism 40.

In the embodiment, after the magnetic bead reagent is put on the machine, an ultrasonic mixing step is arranged, so that the magnetic bead reagent which is not pretreated can be directly put on the machine without pretreatment in advance, the full automation of detection is realized, and the detection efficiency is improved. The supersound mixing is compared traditional manual rocking and vortex mixing and can be more even with the magnetic bead dispersion in the magnetic bead reagent, more can guarantee the accuracy that detects.

In one embodiment, a sample analysis method is provided, which is performed by the sample analyzer of the above-described embodiments. The sample analysis method includes the magnetic bead reagent mixing method in the above embodiment.

Referring to fig. 16, in the whole machine test, five different test procedures can be supported by the sample analyzer according to different reagent items.

First, one-step separation: and respectively adding the sample S and the reagent R, then carrying out primary incubation and primary magnetic separation operation, and then adding the substrate A, incubating and photometry.

Second, two-step one-step separation: after the sample S is added, adding a reagent R1 in the first step, wherein the reagent R1 is a reagent or a plurality of reagents, and the sample and the reagent R1 are mixed to form a reaction solution for first incubation; after the first incubation, adding a reagent R2 into the mixture in the second step, wherein the reagent R2 is a reagent or a plurality of reagents, and the reagent R2 and the reaction solution after the first incubation form a new reaction solution to perform the second incubation; and performing magnetic separation, adding a substrate A, incubating and photometry on the reaction solution after the second incubation in sequence.

Third, two-step separation: after the sample is filled, the reagent R1 is filled in the first step, the sample and the reagent R1 are mixed to form reaction liquid for first incubation, and first magnetic separation operation is carried out after the first incubation; after the first magnetic separation operation, adding a reagent R2 in the second step, and performing second incubation on a new reaction solution formed by the reagent R2 and the reaction solution subjected to the first magnetic separation; carrying out a second magnetic separation operation on the reaction solution after the second incubation; and (4) sequentially carrying out substrate A filling, incubation and photometry on the reaction solution after the second magnetic separation operation.

Fourth, sample pretreatment: filling a sample S, then filling a pretreatment liquid, and pretreating the sample by the pretreatment liquid to form a sample S'; and adding the reagent R into the pretreated sample S', and then sequentially performing incubation, magnetic separation, substrate A adding, incubation and photometry.

Fifth, sample pre-dilution: injecting a sample S, and then injecting a diluent, wherein the diluent is used for diluting the sample to obtain a sample S' with lower concentration; and adding a reagent into the diluted sample S', and then sequentially performing incubation, magnetic separation, substrate A adding, incubation and photometry.

In the present embodiment, the sample analysis method is controlled and executed by the controller 60, and the one-step magnetic separation is taken as an example for description. The sample analysis method carries out ultrasonic mixing on the incubated reaction solution.

Referring to fig. 17, the sample analysis method of the present embodiment includes the following steps:

s201: a magnetic bead reagent is put on the machine;

the doctor places the reagent vessel 105 containing the non-pretreated magnetic bead reagent into the reagent support mechanism 31.

S202: ultrasonically mixing uniformly;

The operation of ultrasonic mixing is the same as the above embodiment, and different ultrasonic modes are matched for different test items, so as to effectively mix the magnetic bead reagent.

S203: filling a sample;

the first transfer mechanism 81 transfers the new receiving cup 103 on the cup loading mechanism 71 to the sample loading position 101;

the sample dispensing mechanism 22 suctions the sample S from the sample support mechanism 21, and dispenses the suctioned sample S into the receiving cup 103 on the sample application site 101.

There is no inevitable precedence relationship between step S103 and steps S101 and S102, and step S103 may be performed before or after step S101 and S102, or step S103 may be performed simultaneously with step S101 and S102.

S204: adding a reagent;

the reagent dispensing mechanism 32 sucks the magnetic bead reagent R after the ultrasound from the reagent carrying mechanism 31, and fills the magnetic bead reagent R after the ultrasound sucked into the containing cup 103 at the sample adding reagent position in the reaction mechanism 40, and the sample S and the magnetic bead reagent R in the containing cup 103 are mixed to form a reaction solution.

S205: vortex mixing;

the second transfer mechanism 82 transfers the containing cup 103 containing the reaction solution to the mixing position 102;

and (3) carrying out vortex mixing operation on the reaction liquid in the accommodating cup 103 by adopting a vortex mixing device so as to ensure that the sample S and the magnetic bead reagent R fully react.

S206: incubation;

the second transfer mechanism 82 transfers the cup 103 containing the whirled and mixed reaction solution from the mixing position 102 back to the inner ring of the reaction mechanism 40, and performs incubation for a predetermined time.

S207: magnetic separation;

the second transfer mechanism 82 transfers the cup 103 containing the incubated reaction solution from the reaction mechanism 40 to the magnetic separation mechanism 50;

the cleaning liquid dispensing structure of the magnetic separation mechanism 50 dispenses the cleaning liquid into the containing cup 103 having the reaction liquid;

the magnetic attraction structure attracts the reaction compound with the magnetic beads in the containing cup 103 through a magnetic field;

the liquid-absorbing structure discharges substances other than the adsorbed reaction complex and liquid out of the receiving cup 103.

S208: filling a substrate;

the substrate dispensing mechanism of the magnetic separation mechanism 50 dispenses the substrate A into the liquid-absorbed receiving cup 103, and the substrate A luminescently labels the reaction mixture in the reaction solution.

S209: incubation;

the second transfer mechanism 82 transfers the cup 103 containing the reaction solution into which the substrate A is injected from the inside of the magnetic separation mechanism 50 back to the outer periphery of the reaction mechanism 40, and incubates the reaction solution.

S210: performing light measurement;

the reaction mechanism 40 transfers the cup 103 containing the incubated reaction solution to the detection site;

the measuring mechanism 90 detects the luminescent reaction complex in the receiving cup 103;

after the optical measurement is completed, the waste liquid suction mechanism sucks the reaction liquid from the containing cup 103;

the first transfer mechanism 81 transfers the receiving cup 103 from which the reaction solution is discharged, from the reaction mechanism 40 to the cup throwing position 72.

In this embodiment, the sample analysis method includes the magnetic bead reagent mixing method in the above embodiments, so that complete automation of detection is achieved, and detection efficiency is improved. The supersound mixing is compared traditional manual rocking and vortex and is mixed can be more even with the magnetic bead dispersion in the magnetic bead reagent, more can guarantee the accuracy that detects.

In one embodiment, in step 202, a sampling needle is connected to the ultrasonic apparatus 10, and the sampling needle is used to emit ultrasonic waves into the non-pretreated magnetic bead reagent on the reagent support 31. The ultrasonic mixing operation can also be performed on the magnetic bead reagent which is not pretreated.

In one embodiment, the ultrasonic device 10 is provided in plurality, and the ultrasonic device 10 is further configured to perform an ultrasonic mixing operation on the reaction liquid. If one is disposed near the mixing location 102, the ultrasonic apparatus 10 is further configured to perform an ultrasonic mixing operation on the reaction solution before or after the incubation, and to perform an ultrasonic mixing operation on the reaction solution to which the substrate is added.

In one embodiment, a method for uniformly mixing a magnetic bead reagent is provided, and the method for uniformly mixing a magnetic bead reagent is different from the method for uniformly mixing a magnetic bead reagent in the above embodiment in that: the non-pretreated magnetic bead reagent is firstly placed in the reagent buffer mechanism 33, and after the non-pretreated magnetic bead reagent in the reagent buffer mechanism 33 is subjected to ultrasonic blending operation, the magnetic bead reagent subjected to ultrasonic blending is transferred into the reagent bearing mechanism 31.

Referring to fig. 18, the sample analysis method of the present embodiment includes the following steps:

s301: a magnetic bead reagent is put on the machine;

the physician places the reagent container 105 containing the non-pretreated magnetic bead reagent into the reagent buffer mechanism 33.

S302: ultrasonically mixing uniformly;

the ultrasonic device 10 emits ultrasonic waves into the non-pretreated magnetic bead reagent on the reagent buffer mechanism 33, and performs an ultrasonic mixing operation on the non-pretreated magnetic bead reagent. The ultrasonic device 10 uniformly disperses the magnetic beads in the non-pretreated magnetic bead reagent, so that the subsequent reagent dispensing mechanism 32 can suck the magnetic bead reagent with uniformly distributed magnetic beads.

S303, transferring a magnetic bead reagent;

the reagent transfer mechanism 34 transfers the magnetic bead reagent after the ultrasonic treatment from the reagent buffer mechanism 33 to the reagent holding mechanism 31.

S304: adding a reagent;

In this embodiment, the non-pretreated magnetic bead reagent is ultrasonically mixed in the reagent buffer mechanism 34, and the magnetic bead can be uniformly mixed before the magnetic bead reagent is filled into the sample, so that the magnetic bead reagent sucked by the reagent separate-injection mechanism 32 can fully react with the sample, and the detection accuracy is further improved.

In one embodiment, a sample analysis method is provided, and the sample analysis method includes the method for mixing a magnetic bead reagent in the above embodiment.

Referring to fig. 19, the sample analysis method of the present embodiment includes the following steps:

s401: a magnetic bead reagent is put on the machine;

S402: ultrasonically mixing uniformly;

the ultrasonic device 10 transmits ultrasonic waves to the non-pretreated magnetic bead reagent on the reagent buffer mechanism 33, and performs ultrasonic mixing operation on the non-pretreated magnetic bead reagent. The ultrasonic device 10 uniformly disperses the magnetic beads in the non-pretreated magnetic bead reagent, so that the subsequent reagent dispensing mechanism 32 can suck the magnetic bead reagent with uniformly distributed magnetic beads.

S403: transferring the magnetic bead reagent;

S404: filling a sample;

the sample dispensing mechanism 22 suctions the sample S from the sample support mechanism 21, and dispenses the suctioned sample S into the receiving cup 103 at the sample application site 101.

There is no inevitable precedence relationship between step S204 and steps S201 to S203, and step S204 may be performed before or after step S201 and step S203, or step S204 may be performed simultaneously with step S201 and step S203.

S405: adding a reagent;

S406: vortex mixing;

S407: incubation;

S408: magnetic separation;

the second transfer mechanism 82 transfers the holding cup 103 containing the incubated reaction solution from the reaction mechanism 40 to the magnetic separation mechanism 50;

S409: filling a substrate;

S410: incubation;

the second transfer mechanism 82 transfers the cup 103 containing the reaction solution into which the substrate A is injected from the inside of the magnetic separation mechanism 50 back to the outer periphery of the reaction mechanism 40, and incubates.

S411: performing light measurement;

the measuring mechanism 90 detects the reaction composition emitted in the containing cup 103;

The sample analysis method in this embodiment includes the magnetic bead reagent blending method in the above embodiment, and the magnetic bead reagent that is not preprocessed is ultrasonically blended in the reagent cache mechanism 34, and can also be uniformly blended before the magnetic bead reagent is added into the sample, so that the magnetic bead reagent that is sucked by the reagent dispensing mechanism 32 can sufficiently react with the sample, and further the detection accuracy is improved.

The present invention has been described in terms of specific examples, which are provided to aid in understanding the invention and are not intended to be limiting. Numerous simple deductions, modifications or substitutions may also be made by those skilled in the art in light of the present teachings.

Claims

1. A sample analyzer, comprising:

ultrasonic means for generating ultrasonic vibration to form ultrasonic waves;

2. The sample analyzer of claim 1, wherein the non-pretreated magnetic bead reagents are magnetic bead reagents that have not been subjected to any manual or automated mixing prior to entering the sample analyzer.

3. The sample analyzer of claim 1 or 2, wherein the non-pretreated magnetic bead reagent comprises a magnetic bead reagent having a greater density of magnetic beads at a bottom of the reagent container than at a top of the reagent container.

4. The sample analyzer of claim 1 wherein the reagent support mechanism is configured to support a reagent container containing an unpretreated magnetic bead reagent and the ultrasonic device is configured to perform an ultrasonic operation on the unpretreated magnetic bead reagent on the reagent support mechanism.

5. The sample analyzer of claim 1 further comprising a reagent buffer mechanism for temporarily storing a reagent container containing an unpretreated magnetic bead reagent, the ultrasonic device being configured to perform ultrasonic operations on the unpretreated magnetic bead reagent located on the reagent buffer mechanism, and a reagent transfer mechanism for transferring the ultrasonically operated magnetic bead reagent on the reagent buffer mechanism to the reagent support mechanism.

6. The sample analyzer of claim 1 wherein the controller is configured to obtain test item parameters and perform an ultrasound operation on the non-pretreated magnetic bead reagent according to the test item parameters by matching an ultrasound mode from a predetermined plurality of ultrasound modes.

7. The sample analyzer of claim 6 wherein the plurality of ultrasound modes each have a different ultrasound intensity and/or ultrasound exposure time.

8. The sample analyzer of claim 1 wherein the ultrasonic device comprises an ultrasonic transducer for generating ultrasonic vibrations, a transmission member having a first end and a second end, the first end of the transmission member being connected to the ultrasonic transducer, the second end of the transmission member having an outer diameter smaller than an inner diameter of the reagent container, and a moving device; the moving device is connected with the ultrasonic transducer, the moving device is used for driving the ultrasonic transducer and the transmission piece to move relative to the reagent container, and the second end of the transmission piece can be inserted into the non-pretreated magnetic bead reagent in the reagent container so as to transmit the ultrasonic vibration generated by the ultrasonic transducer to the non-pretreated magnetic bead reagent in the reagent container.

9. The sample analyzer of claim 1 wherein the ultrasonic device comprises an ultrasonic transducer for generating ultrasonic vibrations and a transmission member having a first end and a second end, the first end of the transmission member being connected to the ultrasonic transducer; the second end of the transmission member is used for abutting against the outer wall of the reagent container, and the contact part of the outer wall of the reagent container and the transmission member is a part surrounding the non-pretreated magnetic bead reagent, so that the ultrasonic vibration generated by the ultrasonic transducer is transmitted to the non-pretreated magnetic bead reagent in the reagent container.

10. The sample analyzer of claim 8 or 9 wherein the transmission member is a solid structure, and the outer diameter of the transmission member decreases gradually or in steps from the first end to the second end.

11. The sample analyzer of claim 1 further comprising a sample carrier mechanism for carrying the sample, a sample dispensing mechanism for aspirating the sample from the sample carrier mechanism and discharging the sample into the receiving cup, a reaction mechanism for providing an incubation location for a reaction solution in the receiving cup, the reaction solution comprising the sample and an ultrasonically operated magnetic bead reagent, a magnetic separation mechanism for injecting a wash solution into the incubated reaction solution to perform a magnetic separation operation, and a measurement mechanism for optically measuring the reaction solution injected with the substrate.

12. The sample analyzer of claim 11, wherein the ultrasonic device is further configured to perform an ultrasonic operation on at least one of the sample, the reaction solution to be incubated, the reaction solution after incubation, the reaction solution into which the washing solution is injected, and the reaction solution into which the substrate is injected.

13. A method for uniformly mixing a magnetic bead reagent is characterized by comprising the following steps:

loading a reagent container containing a magnetic bead reagent without pretreatment onto a sample analyzer;

14. The method of claim 13, wherein the non-pretreated magnetic bead reagent is a magnetic bead reagent that has not been subjected to any manual or automatic mixing prior to entering the sample analyzer.

15. The method of claim 13, wherein the non-pretreated magnetic bead reagent comprises a magnetic bead reagent having a density of magnetic beads at a bottom of the reagent container that is greater than a density of magnetic beads at an upper portion of the reagent container.

16. The method for mixing a magnetic bead reagent as claimed in claim 13, wherein the step of loading the reagent container containing the magnetic bead reagent without pretreatment to a sample analyzer comprises: loading a reagent container containing magnetic bead reagents without pretreatment on a reagent bearing mechanism,

17. The method for mixing a magnetic bead reagent as claimed in claim 13, wherein the step of loading the reagent container containing the magnetic bead reagent without pretreatment to a sample analyzer comprises: loading a reagent container containing magnetic bead reagents without pretreatment on a reagent caching mechanism;

18. A method for mixing a reagent on a magnetic bead as recited in any one of claims 13 to 17, wherein the ultrasonic operation of the ultrasonic device is controlled by:

acquiring test item parameters;

and according to the test item parameters, matching one ultrasonic mode from a plurality of preset ultrasonic modes to perform ultrasonic operation on the magnetic bead reagent without pretreatment.

19. A method for mixing a reagent on a magnetic bead as recited in claim 18, wherein the plurality of ultrasound modes have different ultrasound intensities and/or different ultrasound durations.