CN117511722A

CN117511722A - Molecular diagnostic analyzer and molecular diagnostic method

Info

Publication number: CN117511722A
Application number: CN202210898980.6A
Authority: CN
Inventors: 姜斌; 李朝阳; 李江波
Original assignee: Shenzhen Mindray Bio Medical Electronics Co Ltd
Current assignee: Shenzhen Mindray Bio Medical Electronics Co Ltd
Priority date: 2022-07-28
Filing date: 2022-07-28
Publication date: 2024-02-06

Abstract

The present application relates to a molecular diagnostic analyzer and a molecular diagnostic method. The sample preparation mechanism mixes the original sputum to be tested with the reagent in the sample container to prepare a sputum sample to be tested. The sample transport mechanism transports the sample container loaded with the sputum sample to be tested to the sample pretreatment mechanism. The sample pretreatment mechanism is used for carrying out pretreatment on the sputum sample to be tested. The sample conveying mechanism conveys the sample container loaded with the pre-processed sputum sample to be tested from the sample pre-processing mechanism to a sample feeding station of the sample feeding channel. The sample container positioned at the sample feeding station is conveyed to the sample sucking station of the sample feeding channel by the moving mechanism of the sample feeding channel. The sample sucking and moving mechanism sucks the sputum sample to be detected from a sample container positioned at the sample sucking station and transfers the sputum sample to the nucleic acid extracting mechanism. The nucleic acid extraction mechanism is used for extracting nucleic acid from the sucked sputum sample to be detected. The polymerase chain reaction detection mechanism detects the extracted nucleic acid by polymerase chain reaction. The automatic preparation and sampling of sputum samples are realized.

Description

Molecular diagnostic analyzer and molecular diagnostic method

Technical Field

The present application relates to the field of in vitro diagnostics, and in particular to a molecular diagnostic analyzer and a molecular diagnostic method.

Background

The molecular diagnosis technique is a technique for diagnosing a human body state and a disease by detecting the presence, defect or abnormal expression of a gene by a molecular biological technique using DNA and RNA as diagnostic materials. The basic principle of the molecular diagnosis technology is to detect whether the structure of DNA or RNA is changed, the quantity of DNA or RNA is more or less and the expression function is abnormal, so as to determine whether the abnormal change of the gene level exists in a detected person, and the molecular diagnosis technology has important significance for preventing, predicting, diagnosing, treating and prognosticating diseases. When DNA or RNA of a sample such as virus, bacteria, or tissue cells is obtained, it is necessary to perform pretreatment before molecular diagnosis on a sample such as tissue cells, blood, sputum, throat swab, or anal swab of a human body by a tester.

Taking sputum as an example, in the detection of tuberculosis, respiratory viruses, and the like, it is necessary to collect sputum. Before extracting nucleic acid (DNA or RNA) of tubercle bacillus or virus in the sputum, sucking the sputum, liquefying the sputum by a reagent, and fully exposing bacteria in the sputum; then, wall breaking treatment is performed to release nucleic acid (DNA or RNA) inside the tubercle bacillus or the virus. After nucleic acid substances of tubercle bacillus or virus are obtained through extraction and purification, PCR detection is carried out.

However, all of the above operations are performed manually by the inspector within the biosafety cabinet. The operation has high requirements on laboratory staff and needs stronger biological safety protection requirements. In addition, handling of sputum is also prone to cause strong discomfort to the experimenter.

Disclosure of Invention

To at least partially solve the above technical problem, a first aspect of the present application provides a molecular diagnostic analyzer comprising a sample preparation mechanism, a sample pretreatment mechanism, a sample transport mechanism, a sample introduction channel, a sample pipetting mechanism, a nucleic acid extraction mechanism, a polymerase chain reaction detection mechanism, and a controller, wherein the control is configured to:

controlling the sample preparation mechanism to mix original sputum to be tested with a reagent in a sample container so as to prepare a sputum sample to be tested;

controlling the sample conveying mechanism to convey a sample container loaded with a sputum sample to be tested to the sample pretreatment mechanism;

controlling the sample pretreatment mechanism to carry out pretreatment on a sputum sample to be detected in a sample container;

controlling the sample conveying mechanism to convey a sample container loaded with the pretreated sputum sample to be tested from the sample pretreatment mechanism to a sample feeding station of the sample feeding channel;

Controlling a movement mechanism of the sample introduction channel to convey a sample container positioned at the sample introduction station to a sample suction station of the sample introduction channel;

controlling the sample sucking and moving mechanism to suck the pre-processed sputum sample to be detected from a sample container positioned at the sample sucking station and transferring the sucked sputum sample to the nucleic acid extracting mechanism;

controlling the nucleic acid extraction mechanism to extract nucleic acid from the sputum sample to be detected sucked by the sample sucking and moving mechanism;

controlling the polymerase chain reaction detection mechanism to perform polymerase chain reaction detection on the nucleic acid extracted by the nucleic acid extraction mechanism.

A second aspect of the present application provides a molecular diagnostic method comprising:

controlling a sample preparation mechanism to mix original sputum to be tested with a reagent in a sample container so as to prepare a sputum sample to be tested;

controlling a sample conveying mechanism to convey a sample container loaded with a sputum sample to be tested to a sample pretreatment mechanism;

controlling the sample conveying mechanism to convey a sample container loaded with the pretreated sputum sample to be tested from the sample pretreatment mechanism to a sample feeding station of a sample feeding channel;

controlling a sample sucking and moving mechanism to suck the pre-processed sputum sample to be detected from a sample container positioned at the sample sucking station and transferring the sucked sputum sample to be detected to a nucleic acid extracting mechanism;

controlling a nucleic acid extraction mechanism to extract nucleic acid from the sputum sample to be detected, which is sucked by the sample sucking and moving mechanism;

the polymerase chain reaction detection means is controlled to perform polymerase chain reaction detection on the nucleic acid extracted by the nucleic acid extraction means to obtain detection data.

In the molecular diagnosis analyzer and the molecular diagnosis method provided by the application, the sputum sample to be detected can be automatically prepared from the original sputum to be detected and the reagent and the automatically prepared sputum sample to be detected can be automatically conveyed to the sample pretreatment mechanism, so that the sample pretreatment mechanism automatically carries out pretreatment on the sputum sample, manual operation can be reduced, pretreatment efficiency is improved, and discomfort caused by manual operation on the sputum can be reduced. In addition, the pretreated sputum sample can be automatically transported from the sample pretreatment mechanism to the nucleic acid extraction mechanism and further transported to the polymerase chain reaction detection mechanism, so that the PCR detection efficiency is further improved.

Drawings

The present application will be more clearly explained below with reference to examples and drawings. The above-described and other advantages will be apparent to those of ordinary skill in the art from a detailed description of embodiments of the present application. The drawings are only for purposes of illustrating alternative embodiments and are not to be construed as limiting the application.

The same or similar reference numbers will be used throughout the drawings to refer to the same parts. In the drawings:

FIG. 1 shows a schematic block diagram of a first embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 2 shows a schematic block diagram of a second embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 3 illustrates one exemplary process of constructing a polymerase chain reaction system according to the present application;

FIG. 4 shows a schematic block diagram of a third embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 5 shows a schematic block diagram of a first embodiment of a sample preparation mechanism according to the present application;

FIG. 6 shows schematic top and side views of one embodiment of a sample rack according to the present application;

FIG. 7 illustrates one exemplary process for preparing a sputum sample to be tested according to the sample preparation mechanism of the present application;

FIG. 8 shows a schematic block diagram of a fourth embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 9 shows a schematic structural view of a second embodiment of a sample preparation mechanism according to the present application;

FIG. 10 shows a schematic structural view of a third embodiment of a sample preparation mechanism according to the present application;

FIG. 11 shows a schematic block diagram of a fifth embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 12 shows a schematic block diagram of a sixth embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 13 illustrates an exemplary process for automated sample introduction and removal from a sample rack;

FIG. 14 shows a schematic block diagram of a fourth embodiment of a sample preparation mechanism according to the present application;

FIG. 15 is a schematic view showing the structure of one embodiment of a sample size recognition mechanism according to the present application;

FIG. 16 shows a schematic structural view of one embodiment of a reagent pipetting mechanism according to the present application;

FIG. 17 shows a schematic block diagram of a fifth embodiment of a sample preparation mechanism according to the present application;

FIG. 18 shows a schematic structural view of one embodiment of an ultrasonic treatment section according to the present application;

FIG. 19 shows a schematic structural view of another embodiment of an ultrasonic treatment section according to the present application;

Fig. 20 shows a schematic structural view of an embodiment of a blending unit according to the present application;

fig. 21 shows a schematic structural view of another embodiment of a blending unit according to the present application;

FIG. 22 shows a schematic structural view of one embodiment of a stationary unit according to the present application;

FIG. 23 shows a schematic structural view of one embodiment of a centrifugal part according to the present application;

FIG. 24 illustrates a schematic block diagram of one embodiment of a scanning mechanism in accordance with the present application;

FIG. 25 shows a schematic block diagram of a seventh embodiment of a molecular diagnostic analyzer according to the present application;

FIG. 26 illustrates a first exemplary workflow of an analytical diagnostic analyzer according to the present application; and

FIG. 27 illustrates a second exemplary workflow of an analytical diagnostic analyzer according to the present application;

FIG. 28 illustrates an exemplary flow chart of an analytical diagnostic method according to the present application.

Detailed Description

Embodiments of the present application will now be described more fully hereinafter with reference to the accompanying drawings, in which it is shown, however, in which some, but not all embodiments of the application are shown. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments herein without making any inventive effort, are intended to be within the scope of the present application.

It should be noted that, the term "first\second\third" in the embodiments of the present application is merely to distinguish similar objects, and does not represent a specific order for the objects, and it is understood that "first\second\third" may interchange a specific order or sequence where allowed.

It will be understood by those skilled in the art that all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs unless defined otherwise.

As mentioned in the background art, in the existing molecular diagnostic analyzers, manual preparation and manual pretreatment of sputum samples by laboratory staff are often required, which not only reduces the detection efficiency, but also easily causes discomfort to the staff. In addition, the manual preparation and the manual pretreatment are required to be carried out in a biosafety cabinet, and have high requirements on biosafety protection, so that the detection cost is increased.

To this end, the present application provides an automated molecular diagnostic analyzer. As shown in fig. 1, the molecular diagnostic analyzer 1000 includes a sample preparation mechanism 1010, a sample pretreatment mechanism 1020, a sample transport mechanism 1030, a sample introduction channel 1040, a sample pipetting mechanism 1050, a nucleic acid extraction mechanism 1060, a polymerase chain reaction detection mechanism 1070, and a controller 1080.

The sample preparation mechanism 1010 is used to prepare a sputum sample to be tested in the sample container 10.

The sample pretreatment mechanism 1020 is used for pretreating the sputum sample to be tested.

The sample transport mechanism 1030 is used for transporting the sample container 10 loaded with the sputum sample to be tested to the sample pretreatment mechanism 1020, and transporting the sample container 10 loaded with the pre-treated sputum sample to be tested from the sample pretreatment mechanism 1020 to the sample introduction channel 1040.

The sample introduction path 1040 includes a sample introduction station 1041 provided corresponding to the sample pretreatment mechanism 1020, a sample suction station 1042 provided corresponding to the nucleic acid extraction mechanism 1060, and a movement mechanism 1043. Here, the sampling station 1041 is used to receive the sample container 10 conveyed by the sample conveying mechanism 1030, that is, the sample conveying mechanism 1030 is used to convey the sample container 10 loaded with the pre-processed sputum sample to be tested to the sampling station 1041. The movement mechanism 1043 is used for conveying the sample container 10 located at the sample introduction station 1041 to the sample suction station 1042.

The sample pipetting mechanism 1050 is used for pipetting the pre-processed sputum sample to be tested from the sample container 10 at the pipetting station 1042 and transferring the pipetting sputum sample to the nucleic acid extraction mechanism 1060.

The nucleic acid extraction mechanism 1060 is used for extracting nucleic acid from the sputum sample to be tested sucked by the sample pipetting mechanism 1050. The polymerase chain reaction detection mechanism 1070 is used for performing polymerase chain reaction detection on the nucleic acid extracted by the nucleic acid extraction mechanism 1060.

The controller 1080 is communicatively coupled to and configured to control the operation of the sample preparation mechanism 1010, the sample pretreatment mechanism 1020, the sample transport mechanism 1030, the sample introduction channel 1040, the sample pipetting mechanism 1050, the nucleic acid extraction mechanism 1060, and the polymerase chain reaction detection mechanism 1070.

That is, the controller 1080 is configured to:

control sample preparation mechanism 1010 to mix the raw sputum to be tested with a reagent (including, for example, a liquefied reagent) in sample container 10 to prepare a sputum sample to be tested;

control the sample transport mechanism 1030 to transport the sample container 10 loaded with the sputum sample to be tested to the sample pretreatment mechanism 1020;

the sample pretreatment mechanism 1020 is controlled to carry out pretreatment on the sputum sample to be tested in the sample container 10;

the sample transport mechanism 1030 is controlled to transport the sample container 10 loaded with the pre-processed sputum sample to be tested from the sample pre-processing mechanism 1020 to the sample introduction station 1041 of the sample introduction channel 1040;

The motion mechanism 1042 controlling the sample channel 1040 conveys the sample container 10 located at the sample station 1041 to the sample suction station 1041 of the sample channel 1042;

the sample pipetting mechanism 1050 is controlled to aspirate the pre-processed sputum sample to be tested from the sample container 10 at the aspiration station 1041 and transfer the aspirated sputum sample to the nucleic acid extraction mechanism 1060;

control the nucleic acid extraction mechanism 1060 to extract nucleic acid from the sputum sample to be tested that is sucked by the sample pipetting mechanism 1050;

the polymerase chain reaction detection mechanism 1070 is controlled to detect the polymerase chain reaction of the nucleic acid extracted by the nucleic acid extraction mechanism 1060.

In the molecular diagnostic analyzer 1000 provided in the present application, by providing the sample preparation mechanism and the sample transport mechanism, a sputum sample to be measured and a sample container containing the sputum sample to be measured can be automatically prepared and automatically transferred, so that the sample container can be automatically transported to the sample pretreatment mechanism so that the sample pretreatment mechanism automatically pretreats the sputum sample, and the sample container loaded with the processed sputum sample can be automatically transported to the sample introduction passage, and further, to the nucleic acid extraction mechanism through the sample introduction passage. The whole process is completed completely and automatically without personnel participation, so that the detection efficiency is greatly improved, and the biological protection requirement is reduced.

Further, as shown in fig. 2, the molecular diagnostic analyzer 1000 may further include a consumable management mechanism 1090, a reagent storage mechanism 1100, and a system construction mechanism 1110. Wherein consumable administration 1090 is used to store and supply reaction tubes and nozzles. The reagent storage mechanism is used for storing reagents required by polymerase chain reaction, such as primers and fluorescent probes, 4 dNTPs, taq DNA polymerase and the like. The system construction mechanism 1110 is used for preparing a polymerase chain reaction system, and for sucking up a reagent from the reagent storage mechanism 1100 by using a first suction nozzle supplied from the consumable management mechanism 1090 and transferring the sucked up reagent into a reaction tube supplied from the consumable management mechanism, and also for sucking up a nucleic acid extracted by the nucleic acid extraction mechanism 1060 into the reaction tube filled with the reagent by using a second suction nozzle supplied from the consumable management mechanism 1090, to prepare a sample liquid to be measured.

In the embodiment shown in FIG. 2, the polymerase chain reaction detection mechanism 1070 is also used for performing polymerase chain reaction detection on the sample liquid to be detected prepared by the system construction mechanism 1110 to obtain detection data. The controller 1080 is configured to obtain a nucleic acid detection result of the sample liquid to be detected based on the detection data, and output the nucleic acid detection result.

That is, controller 1080 is also communicatively coupled to architecture construction 1110 and is further configured to:

after controlling the nucleic acid extraction mechanism 1060 to extract nucleic acid and before controlling the polymerase chain reaction detection mechanism 1070 to perform polymerase chain reaction detection on the extracted nucleic acid, controlling the system construction mechanism 1110 to aspirate a reagent from the reagent storage mechanism 1100 by using a first nozzle supplied from the consumable management mechanism 1090 and transfer the aspirated reagent into a reaction tube supplied from the consumable management mechanism 1090, and aspirating the nucleic acid extracted by the nucleic acid extraction mechanism 1060 into the reaction tube containing the reagent by using a second nozzle supplied from the consumable management mechanism 1090 to prepare a sample liquid to be measured;

controlling the polymerase chain reaction detection mechanism 1070 to perform polymerase chain reaction detection on the sample liquid to be detected prepared by the system construction mechanism 1110 so as to obtain detection data; and is also provided with

And acquiring a nucleic acid detection result of the sample liquid to be detected based on the detection data, and outputting the nucleic acid detection result.

In a specific example, the system construction mechanism 1110 is also used to place a reaction tube containing a prepared sample fluid to be tested into the polymerase chain reaction detection mechanism 1070 for nucleic acid amplification and real-time fluorescence detection. During the nucleic acid amplification and real-time fluorescence detection, each nucleic acid amplification cycle signal is read, thereby obtaining a fluorescence amplification graph. The controller 1080 obtains a negative or positive qualitative result from the fluorescent amplification curve, or obtains a quantitative analysis result from the calibration curve, and the concentration of the measured substance in the sample to be measured.

Further, in the embodiment shown in FIG. 2, the molecular diagnostic analyzer 1000 may further include a waste storage mechanism 1120 for storing used reaction tubes and/or nozzles. The system build mechanism 1110 is also used to transport the used reaction tubes and nozzles to a waste storage mechanism 1120.

In an embodiment of the present application, the controller 1080 may include a processing component, which may be a CPU, a GPU, or other chip with an operation capability, and a memory, in which various computer programs such as an operating system and application programs for execution by the processor component and data required for executing the computer programs are installed. In addition, in the data analysis process, if the information needs to be stored locally, the information can be stored in a memory.

In some embodiments, the architecture build mechanism 1110 may also include an open-close lid assembly, not shown, for opening and closing the top lid of the reaction tube.

FIG. 3 illustrates an exemplary process for constructing a polymerase chain reaction system. After nucleic acid extraction, the consumable management mechanism 1090 delivers a reaction tube 20 and corresponding TIP or nozzle 30 under the control of the controller 1080, as shown in fig. 3 a. The system construction mechanism 1110 opens the top cover 21 of the reaction tube 20, and then sucks the reagent from the reagent storage mechanism 1100 using one TIP pipette 31 supplied from the consumable management mechanism 1090 and injects the sucked reagent into the opened reaction tube 20, as shown in fig. 3 b. Next, the system construction mechanism 1110 discards the used TIP chip 31 in the waste storage mechanism 1120, and then aspirates the nucleic acid (e.g., target sequence DNA) extracted by the nucleic acid extraction mechanism 1060 into the reagent-containing reaction tube 20 using another TIP chip 32 supplied from the consumable management mechanism 1090 so as to be well mixed with the reagent in the reaction tube 20 (not limited to blow mixing, vibration mixing, etc.), as shown in FIG. 3 c. The system build mechanism 1110 then discards the used TIP TIPs 32 to the waste storage mechanism 1120 and caps the top caps 21 of the reaction tubes 20 (or alternatively, the reaction tubes 20 may be capped instead of capped) as shown in fig. 3 d. Finally, the system construction mechanism 1110 places the reaction tube 30 covered with the top cover 2 into the polymerase chain reaction detection mechanism 1070 for nucleic acid amplification and real-time fluorescence detection.

In some embodiments, as shown in fig. 4, the sample preparation mechanism 1010, the sample pretreatment mechanism 1020, and the sample transport mechanism 1030 are housed in a single housing 101, the housing 101 having an outlet 103 for outputting a sample container and a closable inlet 104 for placing a sample container into the first receiving area 1011, so that a user can place a sample container through the inlet 104. And the nucleic acid extraction mechanism 1060 and the polymerase chain reaction detection mechanism 1070 are disposed outside the housing 101, and in particular, the nucleic acid extraction mechanism 1060, the polymerase chain reaction detection mechanism 1070, the consumable management mechanism 1090, the reagent storage mechanism 1100, the system construction mechanism 1110, and the waste storage mechanism 1120 are disposed outside the housing 101. For example, the sample preparation mechanism 1010, the sample pretreatment mechanism 1020, and the sample transport mechanism 1030 are housed in the first housing 101, while the nucleic acid extraction mechanism 1060 and the polymerase chain reaction detection mechanism 1070, particularly the nucleic acid extraction mechanism 1060, the polymerase chain reaction detection mechanism 1070, the consumable management mechanism 1090, the reagent storage mechanism 1100, and the system build mechanism 1110 are housed in the second housing 102.

By providing the sample preparation mechanism 1010, the sample pretreatment mechanism 1020, and the sample transport mechanism 1030 in a single closed housing that includes only an outlet for outputting a sample to be tested and an inlet for inputting a sample to be tested, it is possible to prevent aerosol escaping of some biological particles that contain a hazard or unknown during handling of a sputum sample.

Further, in the embodiment shown in fig. 4, the sample introduction station 1041 is disposed inside the housing 101, while the sample suction station 1042 is disposed outside the housing 101, and the sample introduction channel 1043 extends through the outlet 103.

In some embodiments, not shown, molecular diagnostic analyzer 1000 also includes a filtering mechanism for filtering air in housing 101 to prevent environmental contamination. In a specific example, the filter mechanism may be configured as a vent system for maintaining a negative pressure within the housing 101 to avoid escape of air mixed with contaminating aerosols. Here, the housing 101 further includes an air outlet connected to the air exhaust system, and the air outlet is provided at an upper portion of the housing 101, for example.

As is known, before nucleic acid (DNA or RNA) extraction of tubercle bacillus or virus in sputum, it is necessary to aspirate the sputum and liquefy the sputum with a reagent so that pathogens in the sputum are sufficiently exposed.

In the present embodiment, the sputum sample to be tested refers to sputum that has been treated with a reagent (including, for example, a liquefying reagent), and the original sputum to be tested refers to sputum collected from a subject that has not been treated with a reagent (including, for example, a liquefying reagent).

Some examples of the structure of preparing a sputum sample to be tested from an original sputum to be tested are described below, but the present application is not limited to these examples.

In some embodiments, as shown in fig. 5, the sample preparation mechanism 1010 includes a first receiving area 1011 for receiving a plurality of sputum cassettes 30 for loading raw sputum to be tested and for receiving a plurality of sample containers 10, and a sample pipetting portion 1012. The sample pipetting part 1012 is used for sucking up the original sputum to be tested from the sputum cassette 30 and transferring the sucked original sputum to the corresponding sample container 10, so that the sucked original sputum to be tested is mixed with a reagent (the reagent includes a liquefied reagent, for example) in the sample container to form a sputum sample to be tested. Here, controller 1080 is further configured to, in controlling sample preparation mechanism 1010 to prepare a sputum sample to be tested, perform the following steps: the sample sucking and moving part is controlled to suck and move the original sputum to be detected in the sputum box 30 into the corresponding sample container 10, so that the sucked original sputum to be detected is mixed with the reagent in the sample container 10 to form a sputum sample to be detected.

In some examples, the sample pipetting portion 1012 is configured as a syringe, for example.

Further, as shown in fig. 5 and 6, the first receiving area 1011 is further configured to receive a plurality of sample holders 40, and at least one sputum cassette 30 for loading raw sputum to be tested, at least one sample container 10 for loading a reagent, such as a liquefied reagent, and at least one suction nozzle 50 can be placed on each of the sample holders 40. Wherein the sputum box 30, the sample container 10 and the suction nozzle 50 on each sample rack 40 are in one-to-one correspondence. For example, in the embodiment shown in fig. 6, two sputum cassettes, two sample containers, and two suction nozzles are placed on each sample rack 40, respectively, wherein the first sputum cassette 31, the first sample container 11, and the first suction nozzle 51 are provided in a mating arrangement, and the second sputum cassette 32, the second sample container 12, and the second suction nozzle 52 are provided in a mating arrangement. Of course, more than two sets of sputum box-sample container-nozzle assemblies may be provided on each sample rack 40, and the application is not limited thereto.

In the embodiment of fig. 5 and 6, the sample pipetting portion 1012 is configured to aspirate the raw sputum to be tested in the sputum cassette 30 on each sample rack 40 into the sample container 10 on the sample rack using the suction nozzle 50 on the sample rack so that the aspirated raw sputum to be tested mixes with the reagent in the sample container to form a sputum sample to be tested. Here, controller 1080 is further configured to, in controlling sample preparation mechanism 1010 to prepare a sputum sample to be tested, perform the following steps: the control sample sucking and moving part 1012 sucks and moves the original sputum to be tested in the sputum box on each sample rack into the sample container on the sample rack by utilizing the suction nozzle on each sample rack, so that the sucked original sputum to be tested is mixed with the reagent in the sample container to form a sputum sample to be tested.

In this case, reagents, for example liquefied reagents, may already be stored in the sample container 10 on the sample carrier, or the reagents may be pipetted into the sample container 10 on the sample carrier by means of a further pipetting mechanism before or after the addition of the original sputum to be measured.

Further, the sample preparation mechanism 1010 may further include a first cover opening part 1013 for opening and closing the top cover 11 of the sample container 10 so that the sample pipetting part 1012 can transfer the original sputum to be measured sucked from the sputum cassette 30 into the sample container 10 after the cover opening.

In some embodiments, the first cover cap 1013 may be configured as a mechanical jaw that is movable in horizontal and vertical directions and rotatable, for example.

Alternatively or additionally, the sample preparation mechanism 1010 may also include a second cover opening portion, not shown, for opening and closing the top cover of the sputum cassette 30 so that the sample pipetting portion 1012 can aspirate the raw sputum to be measured in the sputum cassette 30. However, in other embodiments, in order to prevent aerosol contamination, the sample may be sucked by directly piercing the cap of the sputum cassette, for example, the cap of the sputum cassette, particularly the middle portion of the cap, may be constructed of a pierceable material or a pierceable structure so as to pierce the sample.

Fig. 7 illustrates an exemplary process of preparing a sputum sample to be tested by the sample preparation mechanism 1010 illustrated in fig. 5 and 6. First, under the control of the controller 1080, the sample pipetting part 1012 moves to the suction nozzle 50 in the sample rack 40 to be tested, so that the sample pipetting part 1012 engages with the suction nozzle 50 as shown in fig. 7 a. Then, as shown in fig. 7b, the first cover part 1013 is moved to the sample container 10 in the sample rack 40 to be tested, the sample container 10 is gripped from the sample rack 40 to be tested and transferred to a holder 01 for gripping the sample container 10, which may be provided in the liquefying part, for example, in a mixing unit to be described later, or which may be provided as a separate gripping mechanism for gripping the sample container. Next, as shown in fig. 7c and 7d, the first cap part 1013 opens the top cover 11 of the sample container 10 located on the fixing base 01 by a rotational movement, and the sample pipetting part 1012 quantitatively aspirates the raw sputum to be tested from the sputum box 30 in the sample rack 40 to be tested by the engaged suction nozzle 50 and injects it into the sample container 10 of the cap. Subsequently, as shown in fig. 7e, the first cap part 1013 again caps the top cap 11 on the sample container 10 by the rotating motion, and the sample pipetting part 1012 discards the used suction nozzle 50.

In some embodiments, as shown in fig. 8, the sample preparation mechanism 1010 may further include a second receiving area 1014 for receiving a sample container 10 into which a sputum sample to be tested is drawn. And the molecular diagnostic analyzer 1000 may further include an unloading mechanism 1130 for unloading the sample container 101 having the sputum sample to be tested sucked into the second accommodation area 1014.

As some implementations, as shown in fig. 9, the first receiving area 1011 may be disposed above the second receiving area 1014, and the unloading mechanism 1130 may be configured as a support table that can be lifted between the first receiving area 1011 and the second receiving area 1014 in order to unload the sample container 10, which has been suctioned the sputum sample to be measured, downward from the first receiving area 1011 into the second receiving area 1014.

In one particular unloading process, support stand 1130 is first raised into alignment with first receiving area 1011 and then sample transport mechanism 1030 places sample container 10 to be unloaded onto the support stand, as shown in FIG. 9 a. The support table is then lowered into alignment with the second receiving area 1014 and finally the sample container 10 on the support table is pushed into the second receiving area 1014, for example by a push rod 1131 provided additionally, as shown in fig. 9 b.

As further implementations, as shown in fig. 10, the first receiving area 1011 may also be disposed horizontally side-by-side with the second receiving area 1014. At this time, the unloading mechanism 1130 may be configured, for example, as a push rod 1131 for pushing the sample container 10 to be unloaded from the first accommodation region 1011 into the second accommodation region 1014.

As still other implementations, the second accommodation region 1014 for accommodating the sample container 10 to which the sputum sample to be measured is sucked may not be provided, and the sample container 10 to which the sputum sample to be measured is sucked may be returned to the first accommodation region 1011 by the sample transport mechanism 1030.

Further, the moving mechanism 1043 may be further used to transport the sample container 10 that is located at the sample sucking station 1042 and is sucked with the sputum sample to be tested to the sample feeding station 1041, so that the sample transporting mechanism 1030 may place the sample container 10 that is located at the sample feeding station 1041 and is sucked with the sputum sample to be tested (i.e. to be unloaded) onto the supporting table 1030 or directly back into the first accommodating area 1011.

In some embodiments, the movement mechanism 1043 may be configured as a receptacle (not shown) that can move back and forth between the sample introduction station 1041 and the sample suction station 1042, the receptacle having at least one receiving aperture for receiving a sample container. The receptacle may be fixed, for example, to a rail for back and forth movement between the sample introduction station 1041 and the sample suction station 1042.

In some embodiments, as shown in fig. 11, the sample transport mechanism 1030 includes a first transport portion 1031 and a second transport portion 1032, wherein the first transport portion 1031 is configured to transport the sample container 10 loaded with the sputum sample to be tested from the first receiving area 1011 to the sample pre-processing mechanism 1020, and the second transport portion 1032 is configured to transport the sample container 10 loaded with the pre-processed sputum sample to be tested from the sample pre-processing mechanism 1020 to the sample introduction channel 1040.

Here, the first conveying portion 1031 and the second conveying portion 1032 may be the same conveying portion, for example, configured as the same robot capable of three-dimensional movement. Alternatively, the first and second conveying portions 1031 and 1032 may be configured independently of each other, for example, the first conveying portion 1031 is configured as a first robot capable of three-dimensional movement, and the second conveying portion 1032 is configured as a second robot capable of three-dimensional movement.

Alternatively or additionally, in the embodiment shown in fig. 11, the sample pipetting mechanism 1050 may comprise a sampling tube 1051 and a drive 1052, wherein the sampling tube 1051 is for aspirating a pre-processed sputum sample to be tested from a sample container located at a sampling station 1042 and the drive 1052 is for driving the movement of the sampling tube to transfer the aspirated sputum sample to the nucleic acid extraction mechanism.

In some examples, the sampling tube 1051 is configured, for example, as a syringe.

Further, in the embodiment shown in fig. 11, the sample conveying mechanism 1030 may further include a third conveying portion 1033, the third conveying portion 1033 being independent of the first conveying portion 1031. The third conveying section 1033 is used for conveying the sample containers 10 in the first accommodation region 1011 to the pretreatment stations 1015 provided in the first accommodation region, respectively, and the first conveying section 1031 is also used for conveying the sample containers located at the pretreatment stations 1015 to the sample pretreatment mechanism 1020. The pretreatment station 1015 is disposed on a support stand 1130, for example.

For example, the third transfer portion 1033 may be configured as a belt transfer portion over which the first receiving area 1011 is formed. For another example, the first receiving area 1011 is formed by a support plate, and the third carrying portion 1033 may be configured as a toggle assembly below the support plate, in which a through hole is opened, through which the toggle assembly can toggle the sample container on the support plate.

In some embodiments, as shown in fig. 12, the second accommodation region 1014 is for accommodating the sample rack 40 in which the sample container 10 having the sputum sample to be measured sucked is placed, and the unloading mechanism 1130 is for unloading the sample rack 40 in which the sample container 10 having the sputum sample to be measured sucked is placed from the first accommodation region 1011 into the second accommodation region 1014. Further, the first transporting section 1031 is also used for transporting the sample container 10 having the sputum sample sucked up to be tested back onto the corresponding sample rack 40 located at the pretreatment station 1015, and the unloading mechanism 1130 is also used for unloading the sample rack 40 located at the pretreatment station 1015, in which the sample container 10 having the sputum sample sucked up to be tested is placed, into the second accommodation area 1014.

Here, the controller 1080 may be further configured to perform the following steps when controlling the sample transport mechanism 1030 to transport the sample container 10 loaded with the pre-processed sputum sample to be tested from the sample pre-processing mechanism 1020 to the sample station 1041 of the sample channel 1040: the first transfer section 1031 is controlled to transfer the sample rack 40 in the first accommodation region 1011 to the pretreatment station 1015 provided in the first accommodation region 1011; and controlling the second transporting section 1032 to transport the sample containers 10 located on the sample racks 40 of the pretreatment station 1015 to the sample pretreatment mechanism 1020. The controller 1080 may also be configured to: the motion mechanism 1042 is controlled to convey the sample container which is positioned at the sample suction station 1043 and is sucked with the sputum sample to be detected to the sample suction station 1041; the second conveying part 1032 is controlled to convey the sample container which is positioned at the sample introduction station 1041 and is sucked with the sputum sample to be tested back to the corresponding sample rack positioned at the pretreatment station 1015; and the unloading mechanism 1130 is controlled to unload the sample rack 40, which is located at the pretreatment station 1015 and in which the sample container of the sputum sample to be tested is placed, into the second accommodation area 1014.

Referring again to fig. 9, the first receiving region 1011 may be disposed above the second receiving region 1014, and the unloading mechanism 1130 may be configured as a support table that can be lifted between the first receiving region 1011 and the second receiving region 1014 so as to unload the sample rack 40, in which the sample container 10 having the sputum sample to be measured sucked is placed, downward from the first receiving region 1011 into the second receiving region 1014.

Further, the third conveying portion 1033 is used for conveying the sample racks 40 in the first accommodation region 1011 to the pretreatment station 1015, and the first conveying portion 1031 is used for conveying the sample containers 10 located on the sample racks 40 of the pretreatment station 1015 to the sample pretreatment mechanism.

Fig. 13 illustrates an exemplary process for automated sample introduction and removal of the sample rack 40. In the example shown in fig. 13, the unloading mechanism 1130 is a support table as described above, and the pretreatment station 1015 is provided on the support table. After starting the sputum test procedure, the sample transport mechanism 1030 first transports the sample rack 40 to be tested onto the support stand 1130 aligned with the first receiving area 1011 under the control of the controller 1080, as shown in fig. 13 a. Next, the sample preparation mechanism 1010 prepares a sputum sample to be tested according to the exemplary process shown in fig. 7, as shown in fig. 13 b. Next, the sample transport mechanism 1030 transports the sample container 10 loaded with the sputum sample to be tested to the sample pretreatment mechanism 1020 for pretreatment, and transports the sample container 10 loaded with the pretreated sputum sample to be tested from the sample pretreatment mechanism 1020 to the sample introduction station of the sample introduction channel 1040. The sample introduction path 1040 transports the sample container 10 loaded with the pre-processed sputum sample to be tested from the sample introduction station to the sample suction station so that the sample pipetting mechanism 1050 sucks the pre-processed sputum sample to be tested from the sample container 10 located at the sample suction station. Subsequently, the sample introduction channel 1040 conveys the sample container 10 having the sputum sample to be tested sucked up from the sample suction station back to the sample introduction station. Next, the sample transport mechanism 1030 transports the sample container 10, which is located at the sample introduction station and has sucked up the sputum sample to be tested, back onto the corresponding sample rack 40 located at the support stand 1130, as shown in fig. 13 c. Support 1130 is then moved downwardly into alignment with second receiving area 1014, and sample rack 40 on support 1130 is then pushed into second receiving area 1014, for example by a push rod 1131 provided additionally, as shown in fig. 13d and 13 e. Finally, the support stand 1130 is moved up into alignment with the first receiving area 1011, i.e., reset, as shown in fig. 13f, so that the sample transport mechanism 1030 transports the next sample rack 40 to be tested onto the support stand 1130 aligned with the first receiving area 1011.

Alternatively to the embodiment of fig. 5 and 6, as shown in fig. 14, 15 and 16, the sample container 10 may be configured to load a sputum cassette 30 of raw sputum to be tested, and the sample preparation mechanism 1010 includes a first receiving area 1011, a sample size identification mechanism 1140 and a reagent pipetting mechanism 1150. The first accommodating area 1011 is used for accommodating a plurality of sputum cassettes 30 for loading original sputum to be tested, the sample amount identifying mechanism 1140 is used for identifying the original sputum amount in the sputum cassettes 30, and the reagent pipetting mechanism 1150 is used for pipetting a corresponding amount of reagent, such as liquefied reagent, into the sputum cassettes 30 according to the original sputum amount, so that the pipetted reagent is mixed with the original sputum to be tested in the sputum cassettes to form a sputum sample to be tested. Here, controller 1080 may be further configured to perform the following steps when controlling sample preparation mechanism 1010 to prepare a sputum sample to be tested: the control sample amount recognition section 1140 recognizes the original sputum amount in the sputum cassette 30; and controlling the reagent pipetting part 1150 to pipette a corresponding amount of reagent, for example, a liquefied reagent, into the sputum box 30 according to the original sputum amount so that the pipetted reagent is mixed with the original sputum to be measured in the sputum box to form a sputum sample to be measured.

Further, in the embodiment shown in fig. 14, sample preparation mechanism 1010 further includes a reagent storage area 1016 for storing a reagent, such as a liquefied reagent, and a mouthpiece storage area 1017 for storing disposable mouthpiece 50. The reagent pipetting mechanism 1150 is also used to withdraw a pipette nozzle 50 from the pipette nozzle storage area 1017 and utilize the pipette nozzle 50 to aspirate a corresponding amount of reagent from the reagent storage area 1016 according to the original sputum volume and transfer the aspirated reagent into the sputum cassette 30.

In the embodiment shown in fig. 15, the sample size recognition mechanism 1140 includes a sputum box clamping jaw 1141 and a visual detection module 1142, the sputum box clamping jaw 1141 is used for clamping the sputum box 30 to be tested within the detection range of the visual detection module 1142, and the visual detection module 1142 is used for detecting the sputum amount of the sputum box 30 located within the detection range thereof by a visual detection mode.

In other embodiments, the sample size recognition mechanism 1140 may also use ultrasonic fluid level or weighing to recognize the original sputum in the sputum cassette 30.

In some embodiments, as shown in fig. 14, the sputum cassettes 30 are placed one by one in the first receiving area 1011 in a single form and unloaded into the second receiving area 1014 individually. In other alternative embodiments, it is also possible that a plurality of sputum cassettes 30, for example two sputum cassettes, are placed on a sample rack for loading and unloading.

Alternatively to the embodiment of fig. 5 and 6, as shown in fig. 17, the sample preparation mechanism 1010 may include a first receiving area 1011 and a sample pipetting portion. The first receiving area 1011 may include a first sub-receiving area 10111 for receiving a sample container 10 loaded with a reagent, such as a liquefied reagent, a second sub-receiving area 10112 for receiving the sputum cartridge 30, and a third sub-receiving area 10113 for receiving the suction nozzle 50. Here, the controller is further configured to perform the following steps when controlling the sample preparation mechanism 1010 to prepare a sputum sample to be tested:

The sample sucking and moving part is controlled to suck and move the original sputum to be detected in the sputum box in the second sub-accommodating area into the sample container in the first sub-accommodating area by utilizing the suction nozzle in the third sub-accommodating area, so that the sucked original sputum to be detected is mixed with the reagent in the sample container to form a sputum sample to be detected.

In the embodiment shown in fig. 17, a plurality of sputum cassettes 30, for example, two sputum cassettes, are placed on a sample rack 40 for loading and unloading. It is equally possible, however, for the sputum cassettes 30 to be placed one by one in the second sub-holding section 10112 in a single form. Some embodiments of the sample pretreatment mechanism 1020 of the present application are described next.

In some embodiments, as shown in fig. 18, the sample pretreatment mechanism 1020 includes an ultrasonic treatment portion 1021 for ultrasonic treatment, such as an ultrasonic horn, and the ultrasonic treatment portion 1021 is used for ultrasonic treatment, particularly ultrasonic wall breaking treatment, of the homogenized sputum sample to be tested so as to achieve cell wall lysis of bifidobacteria in the sputum sample.

Further, the ultrasonic processing section 1021 may further include a not-shown standing unit for receiving the sample container 10 loaded with the sample of sputum to be subjected to ultrasonic processing, so that the sample container 10 stands still in the standing unit for a period of time, thereby eliminating the aerosol generated due to ultrasonic processing in the sample container 10.

Based on the embodiments shown in fig. 14, 15 and 16, when the sample container 10 is configured as a sputum cassette 30 for loading raw sputum to be tested, as shown in fig. 19, the ultrasound processing section 1021 may include an ultrasound horn 10211 and a stationary unit 10212.

In some embodiments, as shown in fig. 20, the sample preprocessing mechanism 1020 may further include a mixing unit 1022 for mixing the sputum sample to be tested in the sample container 10 so as to liquefy the sputum sample to be tested.

In a specific example, the pretreatment may include a mixing treatment and a wall breaking treatment, such as an ultrasonic wall breaking treatment. Here, the controller 1080 may be further configured to perform the following steps when controlling the sample preprocessing mechanism 1020 to perform preprocessing on the sputum sample to be measured in the sample container: the control sample pretreatment mechanism 1020 performs a mixing process, for example, by the mixing unit 1022, and then performs a wall breaking process, for example, by the ultrasonic processing unit 1021, on the sputum sample to be measured in the sample container. Here, the sample transport mechanism 1030 is also used to transfer the sample container 10 mixing unit 1022 loaded with the mixed sputum sample to be measured to the ultrasonic processing section 1021.

In some specific examples, the mixing unit 1022 may be configured as a mechanical mixing unit, such as a vortex-oscillating mixing unit or an eccentric mixing unit. Here, as shown in fig. 20, the mixing unit 1022 may include, for example, a base 10221 and a motor 10222, where the base 10221 is used to receive the sample container 10, and the motor 10222 is used to drive the base 10221 to rotate, especially eccentrically rotate, so as to perform a mixing operation on the sputum sample to be measured in the sample container 10.

In other examples, the mixing unit 1022 may also be configured as an ultrasonic mixing unit, not shown.

In still other examples, on the basis of the embodiments shown in fig. 14, 15 and 16, when the sample container 10 is configured as the sputum cassette 30 for loading the raw sputum to be measured, the mixing unit 1022 may be configured as an oscillating mixing module as shown in fig. 21. The mixing unit 1022 shown in fig. 21 may also include a base 10221 and a motor 10222, where the base 10221 is used to receive the sputum box 30, and the motor 10222 is used to drive the base 10221 to rotate, especially eccentrically rotate, so as to perform a mixing operation on the sputum sample to be measured in the sputum box 30.

Further, as shown in fig. 22, the sample pretreatment mechanism 1020 may further include a stationary unit 1023 for accommodating a sample container loaded with the homogenized sputum sample to be tested, so that the reagent is sufficiently incubated with the original sputum. In addition, the stationary unit is provided with a first heating module which is used for heating the evenly mixed sputum sample to be tested so as to improve the effect of incubation reaction. The first heating module is for example used to maintain the temperature of the stationary unit at a preset temperature, for example at about 60 ℃. Here, the sample transport mechanism 1030 is also used to transport sample containers from the mixing unit 1022 to the standing unit 1023.

Alternatively or additionally, the sample pretreatment mechanism 1020 may further include a second heating module, not shown, for heating the sputum sample to 90-100 ℃ to effect microbial inactivation, or cell wall lysis, of the sputum sample.

Of course, in other embodiments, cell wall lysis may be achieved by the addition of chemical reagents, biological enzymes, and the like.

In some embodiments, the pretreatment may further comprise a centrifugal purification process, wherein the controller 1080 may be further configured to, in controlling the sample pretreatment mechanism 1020 to pre-treat the sputum sample to be tested in the sample container, perform the following steps: the sample pretreatment mechanism 1020 is controlled to sequentially carry out uniform mixing treatment, centrifugal purification treatment and wall breaking treatment on the sputum sample to be detected in the sample container.

For this purpose, as shown in fig. 23, the sample pretreatment mechanism 1020 may further include a centrifugal part 1024 for performing centrifugal purification treatment on the homogenized sputum sample to be tested. Here, the sample transport mechanism 1030 is also used to transfer a sample container loaded with the homogenized sputum sample to be measured from the homogenizing unit 1022 or the standing unit 1023 to the centrifugal part 1024, and to transfer a sample container loaded with the homogenized sputum sample to be measured from the centrifugal part 1024 to the ultrasonic processing part 1021. Thus, the tubercle bacillus in the sputum sample can be enriched before the cell wall lysis by the ultrasonic processing section 1021 is achieved.

In some embodiments, as shown in fig. 24, the molecular diagnostic analyzer 1000 further includes a scanning mechanism 1160 configured to scan a barcode of the sample container 10 or sputum cassette 30 to obtain identity information of the sputum sample to be tested in the sample container or sputum cassette. The scanning mechanism 1160 is disposed, for example, within the sample preparation mechanism.

In some embodiments, as shown in fig. 25, the sample preparation mechanism further includes a third receiving area 1018 for receiving a plurality of other sample containers 60 for loading other biological samples different from the sputum sample. The sample transport mechanism 1030 is also used to transport other sample containers 60 to the sample introduction station 1041, and the movement mechanism 1043 is also used to transport other sample containers 60 located at the sample introduction station 1041 to the sample suction station 1042. That is, the sample container 10 for loading a sputum sample and the other sample container 60 for loading other biological samples share the same sample introduction channel 1040.

Two exemplary workflows of the analytical diagnostic analyzer of the present application are described below in connection with fig. 26 and 27.

A first exemplary workflow is described in connection with fig. 5-7, 12-13, and 26. In step S110, the user places a sample rack, in which a sputum cassette loaded with raw sputum, a sample container loaded with a processing reagent, and a disposable nozzle are placed, into the first accommodation zone 1011, and then automatically loads the first sample rack onto the support stand 1130 aligned with the first accommodation zone 1011 by the sample transport mechanism 1030 (e.g., a third transport part) as shown in fig. 13 a. In step S120, the sample preparation mechanism 1010 prepares a sputum sample to be tested according to the exemplary process shown in fig. 7. In step S130, the sample transport mechanism 1030 transports the sample container loaded with the sputum sample to be tested to the mixing unit 1022 for mixing and liquefying, for example, vortex vibration mixing or ultrasonic mixing. In step S140, the sample transport mechanism 1030 transports the homogenized sample container from the homogenizing unit 1022 to the standing unit 1023 for standing incubation so as to be sufficiently liquefied; the stationary unit 1023 has a heating function, and maintains the sample in the sample container within a certain temperature range, thereby promoting liquefaction. In step S150, the sample transport mechanism 1030 transports the sample container subjected to the stationary incubation from the stationary unit 1023 to the ultrasonic processing section 1021 for cell wall lysis, thereby completing the pretreatment of the sputum sample to be tested. In step S160, the sample container subjected to the pretreatment by the sample conveying mechanism 1030 is conveyed from the ultrasonic processing section 1021 to the sample introduction station of the sample introduction passage 1040, and the sample introduction passage 1040 conveys the sample container subjected to the pretreatment from the sample introduction station to the sample suction station, so that the sample pipetting mechanism 1050 sucks the sample of the sputum to be subjected to the pretreatment from the sample container located at the sample suction station. In step S171, the sample introduction path 1040 conveys the sample container having sucked up the sputum sample to be tested from the sample suction station back to the sample introduction station, and then the first sample rack is unloaded according to the process shown in fig. 13c to 13f, so that the next second sample rack in the first sample accommodation area 1011 is automatically loaded later. In step S172, the sample pipetting mechanism 1050 transfers the suctioned sputum sample to be tested to the nucleic acid extracting mechanism 1060, so that the nucleic acid extracting mechanism 1060 performs nucleic acid extraction. In step S173, a polymerase chain reaction system is constructed according to the exemplary procedure shown in fig. 3, so that the sample liquid to be tested prepared by the polymerase chain reaction detection mechanism 1070 performs nucleic acid amplification and real-time fluorescence detection.

A second exemplary workflow is described in connection with fig. 14-16 and fig. 27. In step S210, the user places a sample rack having placed only the sputum cassette loaded with the original sputum into the first accommodation zone 1011, and then automatically loads the first sample rack onto the support stand 1130 aligned with the first accommodation zone 1011 by the sample transport mechanism 1030 (e.g., the third transport part). In step S220, the sample size identifying mechanism 1140 identifies the original sputum size in the sputum box, and the reagent pipetting mechanism 1150 is configured to pipette a corresponding amount of reagent into the sputum box according to the original sputum size, so that the pipetted reagent is mixed with the original sputum to be measured in the sputum box to form a sputum sample to be measured. In step S230, the sample transport mechanism 1030 transports the sputum cassette loaded with the sputum sample to be tested to the mixing unit 1022 for mixing and liquefying, for example, vortex vibration mixing or ultrasonic mixing. In step S240, the sample conveying mechanism 1030 conveys the homogenized sputum box from the homogenizing unit 1022 to the standing unit 1023 for standing incubation so as to be sufficiently liquefied; the stationary unit 1023 has a heating function, and maintains the sample in the sputum box within a certain temperature range, thereby promoting liquefaction. In step S250, the sample transport mechanism 1030 transports the sputum cassette subjected to the stationary incubation from the stationary unit 1023 to the ultrasonic processing section 1021 for cell wall lysis, thereby completing the pretreatment of the sputum sample to be tested. In step S260, the pre-processed sputum cassette is transported from the ultrasonic processing section 1021 to the sampling station of the sampling channel 1040 by the sample transport mechanism 1030, and the pre-processed sputum cassette is transported from the sampling station to the sampling station by the sampling channel 1040, so that the sample pipetting mechanism 1050 aspirates (e.g., by piercing) the pre-processed sputum sample to be tested from the sputum cassette located at the sampling station. In step S271, the sample introduction path 1040 conveys the sputum cassette having sucked up the sputum sample to be tested from the sample suction station back to the sample introduction station, and then unloads the first sample rack for subsequent automatic loading of the next second sample rack in the first sample receiving area 1011, similarly to the process shown in fig. 13c to 13 f. Steps S272 and S273 are the same as steps S172 and S173 shown in fig. 26, and are not described here.

As shown in fig. 28, the present application further provides a molecular diagnostic method comprising:

step S310, controlling the sample preparation mechanism 1010 to mix the original sputum to be tested with a reagent (the reagent includes, for example, a liquefied reagent) in the sample container 10 to prepare a sputum sample to be tested;

step S320, controlling the sample transport mechanism 1030 to transport the sample container loaded with the sputum sample to be tested to the sample pretreatment mechanism 1020;

step S330, controlling the sample pretreatment mechanism 1020 to perform pretreatment on the sputum sample to be tested in the sample container;

step S340, controlling the sample conveying mechanism 1030 to convey the sample container 10 loaded with the pre-processed sputum sample to be tested from the sample pre-processing mechanism 1020 to the sample introduction station 1041 of the sample introduction channel 1040;

step S350, controlling the motion mechanism 1042 of the sample channel 1040 to convey the sample container located at the sample station 1041 to the sample suction station 1043 of the sample channel 1040;

step S360, controlling the sample pipetting mechanism 1050 to aspirate the pre-processed sputum sample to be tested from the sample container at the sample aspiration station 1043 and transfer the aspirated sputum sample to the nucleic acid extraction mechanism 1060;

step S370, controlling the nucleic acid extraction mechanism 1060 to extract nucleic acid from the sputum sample to be tested sucked by the sample sucking mechanism 1050;

In step S380, the polymerase chain reaction detection mechanism 1070 is controlled to detect the polymerase chain reaction of the nucleic acid extracted by the nucleic acid extraction mechanism 1060.

In some embodiments, the pretreatment may include a mixing process and a wall breaking process, wherein controlling the sample pretreatment mechanism 1020 to perform pretreatment on the sputum sample to be tested in the sample container includes:

the control sample pretreatment mechanism 1020 firstly carries out uniform mixing treatment on the sputum sample to be detected in the sample container, and then carries out wall breaking treatment.

In some embodiments, the pretreatment may further comprise a centrifugation purification process, wherein controlling the sample pretreatment mechanism 1020 to pretreatment the sputum sample to be tested in the sample container comprises:

the sample pretreatment mechanism 1020 is controlled to sequentially carry out uniform mixing treatment, centrifugal purification treatment and wall breaking treatment on the sputum sample to be detected in the sample container.

In some embodiments, the wall breaking treatment may be achieved by at least one of ultrasound, high temperature boiling, addition of chemical agents, addition of biological enzymes.

In some embodiments, the molecular diagnostic method may further comprise:

after controlling the nucleic acid extraction mechanism 1060 to extract nucleic acid and before controlling the polymerase chain reaction detection mechanism 1070 to perform polymerase chain reaction detection on the extracted nucleic acid, controlling the system construction mechanism to aspirate a reagent from the reagent storage mechanism by using a first nozzle supplied by the consumable management mechanism and transfer the aspirated reagent into a reaction tube supplied by the consumable management mechanism, and aspirating the nucleic acid extracted by the nucleic acid extraction mechanism into the reaction tube containing the reagent by using a second nozzle supplied by the consumable management mechanism to prepare a sample liquid to be measured;

Controlling a polymerase chain reaction detection mechanism to perform polymerase chain reaction detection on the sample liquid to be detected prepared by the system construction mechanism so as to obtain detection data; and is also provided with

Further embodiments and advantages of the molecular diagnostic methods of the present application may be found in the description of the molecular diagnostic analyzer 1000 of the present application described above, and are not described in detail herein.

The features or combinations of features mentioned above in the description, in the drawings and in the claims may be used in any combination with one another or individually as long as they are significant and do not contradict one another within the scope of the present application.

The foregoing description is only of the preferred embodiments of the present application, and is not intended to limit the scope of the patent application, but is intended to cover all modifications within the scope of the invention, as may be included in the patent application, using the equivalent arrangements of the present application and the accompanying drawings, or by direct/indirect application in other related arts.

Claims

1. A molecular diagnostic analyzer comprising a sample preparation mechanism, a sample pretreatment mechanism, a sample transport mechanism, a sample introduction channel, a sample pipetting mechanism, a nucleic acid extraction mechanism, a polymerase chain reaction detection mechanism, and a controller, wherein the controller is configured to:

2. The molecular diagnostic analyzer of claim 1, wherein the sample preparation mechanism comprises a first receiving area and a sample pipetting portion, wherein the first receiving area is configured to receive a plurality of sputum cassettes for loading raw sputum to be tested and to receive a plurality of sample receptacles; and is also provided with

The controller is further configured to, when controlling the sample preparation mechanism to prepare a sputum sample to be tested, perform the steps of:

and controlling the sample sucking and moving part to suck and move the original sputum to be detected in the sputum box into a corresponding sample container, so that the sucked and moved original sputum to be detected is mixed with a reagent in the sample container to form a sputum sample to be detected.

3. The molecular diagnostic analyzer of claim 2, wherein the first receiving area is further configured to receive a plurality of sample holders, each sample holder being capable of holding at least one sputum cassette for holding raw sputum to be tested, at least one sample container for holding reagents, and at least one suction nozzle; and is also provided with

and controlling the sample sucking and moving part to suck and move the original sputum to be detected in the sputum box on each sample rack into the sample container on the sample rack by utilizing the suction nozzle on each sample rack, so that the sucked and moved original sputum to be detected is mixed with the reagent in the sample container to form a sputum sample to be detected.

4. The molecular diagnostic analyzer of claim 1, wherein the sample container is configured as a sputum cassette for loading raw sputum to be tested, the sample preparation mechanism comprising a first receiving area, a sample volume identification portion, and a reagent pipetting portion, wherein the first receiving area is configured to receive a plurality of sputum cassettes for loading raw sputum to be tested; and is also provided with

controlling the sample amount identification part to identify the original sputum amount in the sputum box; and

and controlling the reagent sucking and moving part to suck and move a corresponding amount of reagent into the sputum box according to the original sputum amount so that the sucked and moved reagent is mixed with the original sputum to be detected in the sputum box to form a sputum sample to be detected.

5. A molecular diagnostic analyzer according to claim 3, wherein the sample preparation mechanism further comprises a second receiving area for receiving a sample rack for receiving a sample container in which a sputum sample to be tested is drawn;

the sample transport mechanism includes a first transport section and a second transport section that are independent of each other, and the molecular diagnostic analyzer further includes an unloading mechanism;

Wherein the controller is further configured to perform the following steps when controlling the sample transport mechanism to transport a sample container loaded with a pre-processed sputum sample to be tested from the sample pre-processing mechanism to a sample introduction station of the sample introduction channel:

controlling the first transporting section to transport the sample rack in the first accommodation area to a pretreatment station provided in the first accommodation area; and

and controlling the second conveying part to convey the sample containers positioned on the sample rack of the pretreatment station to the sample pretreatment mechanism.

6. The molecular diagnostic analyzer of claim 5, wherein the controller is further configured to:

controlling the motion mechanism to convey the sample container which is positioned at the sample suction station and is sucked with the sputum sample to be detected to the sample introduction station;

controlling the second conveying part to convey the sample container which is positioned at the sample introduction station and is sucked with the sputum sample to be tested back to the corresponding sample rack positioned at the pretreatment station; and is also provided with

And controlling the unloading mechanism to unload the sample rack which is positioned at the pretreatment station and is provided with the sample container which is used for sucking the sputum sample to be tested into the second accommodating area.

7. The molecular diagnostic analyzer of claim 5 or 6, wherein the first receiving area is disposed above the second receiving area, and the unloading mechanism is configured as a support table for supporting a sample rack that is liftable between the first receiving area and the second receiving area so as to unload a sample rack from the first receiving area downward into the second receiving area.

8. The molecular diagnostic analyzer of claim 1, wherein,

the sample preparation mechanism comprises a first accommodating area and a sample sucking part, wherein the first accommodating area comprises a first sub-accommodating area for accommodating a sample container loaded with a reagent, a second sub-accommodating area for accommodating a sputum box and a third sub-accommodating area for accommodating a suction nozzle; and is also provided with

and controlling the sample sucking and moving part to suck and move the original sputum to be detected in the sputum box in the second sub-accommodating area into the sample container in the first sub-accommodating area by utilizing the suction nozzle in the third sub-accommodating area so that the sucked original sputum to be detected is mixed with the reagent in the sample container to form a sputum sample to be detected.

9. The molecular diagnostic analyzer of any one of claims 1 to 8, wherein the pre-treatment comprises a blending treatment and a wall breaking treatment, wherein the controller is further configured to, when controlling the sample pre-treatment mechanism to pre-treat the sputum sample to be measured in the sample container, perform the steps of:

and controlling the sample pretreatment mechanism to uniformly mix the sputum sample to be detected in the sample container, and then performing wall breaking treatment.

10. The molecular diagnostic analyzer of claim 9, wherein the pre-processing further comprises a centrifugal purification process, wherein the controller is further configured to, when controlling the sample pre-processing mechanism to pre-process the sputum sample to be tested in the sample container, perform the steps of:

and controlling the sample pretreatment mechanism to sequentially carry out uniform mixing treatment, centrifugal purification treatment and wall breaking treatment on the sputum sample to be detected in the sample container.

11. The molecular diagnostic analyzer according to any one of claims 1 to 10, wherein the sample preparation mechanism, the sample pretreatment mechanism and the sample transport mechanism are contained in a single housing having an outlet for outputting a sample container and a closable inlet for placing a sample container; and is also provided with

The nucleic acid extraction mechanism and the polymerase chain reaction detection mechanism are disposed outside the housing.

12. The molecular diagnostic analyzer of claim 11, wherein the sample introduction station is disposed within the housing, the sample suction station is disposed outside the housing, and the sample introduction channel extends through the outlet.

13. The molecular diagnostic analyzer of claim 11 or 12, further comprising a filter mechanism configured to filter air in the housing.

14. The molecular diagnostic analyzer of claim 13, wherein the filter mechanism is configured as a vent system, and the housing further comprises a vent coupled to the vent system.

15. The molecular diagnostic analyzer of claim 14, further comprising a consumable management mechanism for storing and supplying the reaction tube and the suction nozzle, a reagent storage mechanism for storing reagents required for the polymerase chain reaction, and a system construction mechanism for preparing the polymerase chain reaction system;

Wherein the control is further configured to:

after controlling the nucleic acid extraction mechanism to extract nucleic acid and before controlling the polymerase chain reaction detection mechanism to perform polymerase chain reaction detection on the extracted nucleic acid, controlling the system construction mechanism to aspirate reagent from the reagent storage mechanism by using a first nozzle supplied by the consumable management mechanism and transfer the aspirated reagent into a reaction tube supplied by the consumable management mechanism, and aspirating nucleic acid extracted by the nucleic acid extraction mechanism into a reaction tube containing reagent by using a second nozzle supplied by the consumable management mechanism to prepare a sample solution to be tested;

controlling the polymerase chain reaction detection mechanism to perform polymerase chain reaction detection on the sample liquid to be detected prepared by the system construction mechanism so as to obtain detection data; and is also provided with

16. A method of molecular diagnostics, the method comprising:

the polymerase chain reaction detection mechanism is controlled to detect the polymerase chain reaction of the nucleic acid extracted by the nucleic acid extraction mechanism.

17. The molecular diagnostic method of claim 16, wherein the pretreatment comprises a mixing process and a wall breaking process, wherein controlling the sample pretreatment mechanism to pretreat the sputum sample to be tested in the sample container comprises:

18. The molecular diagnostic method of claim 17, wherein the pretreatment further comprises a centrifugation purification process, wherein controlling the sample pretreatment mechanism to pretreatment the sputum sample to be tested in the sample container comprises:

19. The molecular diagnostic method of any one of claims 16 to 18, further comprising:

after controlling the nucleic acid extraction mechanism to extract nucleic acid and before controlling the polymerase chain reaction detection mechanism to perform polymerase chain reaction detection on the extracted nucleic acid, controlling a system construction mechanism to aspirate a reagent from a reagent storage mechanism by using a first nozzle supplied by a consumable management mechanism and transfer the aspirated reagent into a reaction tube supplied by the consumable management mechanism, and aspirating the nucleic acid extracted by the nucleic acid extraction mechanism into the reaction tube containing the reagent by using a second nozzle supplied by the consumable management mechanism to prepare a sample solution to be measured;