CN218491744U - Sample detection pretreatment equipment and reagent cartridges therein - Google Patents

Abstract

The invention relates to a detection reagent cartridge and equipment, belonging to the technical field of molecular diagnostic equipment. The detection reagent cartridge includes: a liquid storage carousel, which is provided with several liquid tanks for containing liquids and sample tube holes for containing sample tubes; the pipetting device includes a pipette for sucking and discharging liquid; and a box body , the liquid storage turntable is installed in the box body, and the inner space of the box body is divided into an upper cavity above the surface of the liquid storage turntable and a lower cavity below the surface of the liquid storage turntable, and the liquid storage turntable can be made along the inner wall of the box Rotational movement and lifting movement; the liquid pipetting device is fixed on the box body, and the liquid storage turntable and the inner wall of the box form a closed space for the upper cavity; the box body is provided with the upper cavity body-connected sample inlet and a matching cartridge lid for the sample inlet. The cartridge has the advantages of fast detection speed and good sealing performance, and will not cause cross-infection, which solves the problem of contamination.

Description

Sample detection pretreatment equipment and reagent cartridges therein

technical field

The invention relates to the technical field of molecular diagnostic equipment, in particular to a sample detection pretreatment equipment and a reagent cartridge therein.

Background technique

The detection process of pathogens in molecular diagnostics requires cleavage, washing, elution, separation and purification of pathogenic nucleic acids, and the purification steps of pathogens are complicated, time-consuming and low in extraction efficiency. If it is carried out in an open environment The above steps are prone to contamination between samples such as aerosols and splashes, or medical staff are infected by pathogens, and will also affect the purity of the extract, thereby affecting the accuracy of the experimental results.

Based on the above reasons, in the conventional technology, there are also some researches on closed cartridges. For example, in the molecular diagnostic equipment technology, the multi-step pathogen detection method has been integrated into one system. The user only needs to add the sample to the system. The remaining steps are all automatically completed by the system.

Therefore, the cartridges and microfluidic chips for molecular diagnosis adopt airtight, single-use detection cards or detection tubes, which better control cross-over and carry-over contamination. But these test cards, or tubes, often only detect one pathogen at a time.

In the conventional technology, there are also some integrated pathogen detection cartridges, which can realize the extraction, amplification and detection of the nucleic acid to be tested in a closed system, which greatly avoids the contamination of the sample during the extraction and amplification process, and effectively improves The accuracy and operability of nucleic acid detection are improved.

Contents of the invention

Based on this, it is necessary to provide a detection reagent cartridge, which has the advantages of good sealing, can detect multiple samples at the same time, is compatible with multiple reagents, can be open and compatible with various reagents, and does not need to pack the reagents in the card Inside the box, it is versatile for different reagents and will not cause cross-infection, which solves the problems of pathogenic microorganism contamination and operator infection.

A detection reagent cartridge, comprising:

A liquid storage turntable, the liquid storage turntable is provided with several liquid tanks for containing liquids and sample tube holes for containing sample tubes, the sample tube holes and several samples of the liquid tanks surround the liquid storage The rotation axis setting of the turntable;

A liquid pipetting device, comprising a pipette for sucking and discharging liquid, the position of the pipetting head of the pipette corresponds to the position of the liquid tank; and

A box body, the liquid storage turntable is installed in the box body, and the inner space of the box body is divided into an upper cavity above the surface of the liquid storage turntable and a lower cavity below the surface of the liquid storage turntable, the liquid storage turntable Rotational movement and lifting movement can be performed along the inner wall of the box; the pipetting device is fixed on the box body, and the pipetting head is located in the upper cavity, and the liquid storage turntable and the box body The wall makes the upper cavity form a closed space; the box body is provided with a sample inlet communicating with the upper cavity and a cartridge cover matching the sample inlet.

The above detection reagent cartridge is equipped with a cartridge cover. After all the samples are added through the sample inlet, the cartridge can be closed tightly. The subsequent sample pretreatment process is completed inside the cartridge. The cartridge is airtight and pollution-free throughout the process. . Moreover, the detection reagent cartridge mentioned above can cooperate with the rotation of the liquid storage turntable and the sample inlet, without the need for pre-packaged reagents inside the cartridge, which facilitates the adjustment of the cartridge for different detection items.

In one of the embodiments, the liquid tank includes a reagent tank, a reaction tank, and a waste liquid tank. It can be understood that the setting of the number and function of various types of slots in a specific liquid tank can be set according to the requirements of specific testing items. For example, for testing items that generate more waste liquid, a larger waste liquid tank can be designed.

In one of the embodiments, several of the liquid tanks and the sample tube holes form an annular arrangement around the axis of the liquid storage carousel, and the pipette head and the sample inlet are both in the same position as the annular ring. correspond. According to the above settings, the pipette and its pipetting head can be fixed, and all the liquid slots and sample tube holes can correspond to the fixed pipetting head through the rotation of the liquid storage turntable, avoiding the need to move the pipetting head The resulting suction error or operational difficulty. However, the pipetting head in the conventional technology is usually separated from the liquid suction device and connected with a hose. There is a risk of pipe breaking during the movement of the pipetting head, resulting in insufficient pipetting accuracy or insufficient suction.

In one of the embodiments, the pipette is a piston pipette. With the immobilization of the pipetting head and the integrated design of the pipetting piston, the external drive is simpler. It only needs to drive the piston to move in a single direction, which has the advantages of reliable and stable operation. It can be understood that the piston-type pipette can be equipped with equipment such as a syringe, and the accuracy requirement can be adjusted by controlling the diameter of the pipe, that is, the volume of the liquid that can be pipetted by the piston moving the same distance.

In one of the embodiments, there are two pipetting heads, and an escape hole is also provided on the liquid storage carousel. When one of the pipetting heads corresponds to the position of the liquid tank, the other of the pipetting heads The pipetting head corresponds to the position of the avoidance hole. It can be understood that the position of the pipette head remains unchanged when the storage carousel moves up, so if there are two pipette heads, when one pipette head is used to pipette and the other is idle, there will be no corresponding hole position for the idle pipette head If placed, it will conflict with the disk surface of the liquid storage carousel, so the avoidance setting of the pipetting head needs to be considered. As for where to set the avoidance hole, those skilled in the art can set it according to the needs of the specific detection project process, as well as the number and position of the applicable pipetting head. The avoidance hole can be a specially designed hole position, or It can be other reagent tanks, etc. that do not affect the detection process.

At the same time, it can be understood that the number of pipette heads is not limited, and one pipette head can also run to complete all the processes, and two pipette heads can effectively prevent the impurities of the sample from being brought into the pure sample, or more Many pipetting heads can also complete all processes, but the number of pipetting heads will affect the size of the storage carousel and the number of avoidance holes, thus affecting the size of the entire cartridge, which can be set according to the requirements of specific testing items.

In one of the embodiments, the inner wall of the box is further provided with a limiting member for limiting the downward movement of the liquid storage turntable, and the limiting member is arranged in the lower cavity. The limiter is used to prevent the liquid storage carousel from falling out of the box after excessive downward movement. It can be understood that the specific shape and position of the limiter can be set according to conventional techniques in the art.

In one of the embodiments, a turntable sealing ring is provided between the liquid storage turntable and the inner wall of the box, and the liquid storage turntable forms a dynamic seal with the box body. It can be understood that the sealing requirements of the upper cavity can also be achieved by other means in the field, but the dynamic sealing is realized by the rotary disc sealing ring, which is convenient and reliable, and has the advantage of not affecting the movement of the liquid storage rotary disc.

In one embodiment, the detection reagent cartridge further includes a guide bracket, the liquid storage turntable is installed in the box through the guide bracket, and the turntable sealing ring is sleeved on the outer peripheral edge of the guide bracket. It can be understood that the guidance of the liquid storage turntable and the movement of the liquid storage turntable are realized by the guide bracket, which has the advantages of stable movement and convenient installation.

In one of the embodiments, the detection reagent cartridge further includes a sealing cover for sealing the liquid storage carousel, the sealing cover is installed on the guide bracket, and the liquid storage carousel can be opposite to the sealing cover turn. Through the use of the sealing cover, the liquid storage carousel can be sealed after the processing of the sample is completed, so as to realize the overall removal and further reduce the risk of contamination. Moreover, both the liquid storage turntable and the sealing cover are installed on the guide bracket, and they can rotate relative to each other without affecting the rotation of the liquid storage turntable.

In one of the embodiments, the detection reagent cartridge further includes an elastic reset member, one end of the elastic reset member leans against the sealing cover, and the other end leans against the inner wall of the box, and the elastic reset member located in the upper cavity. A downward force can be indirectly exerted on the liquid storage turntable through an elastic return member such as a spring, so that the liquid storage turntable moves down and resets after the pipetting device takes liquid.

In one of the embodiments, the inner wall of the box is also provided with a guide rod for guiding the guide bracket, and the sealing cover is provided with a guide sleeve that cooperates with the guide rod, and the guide rod and the guide sleeve are both provided with in the upper cavity. The guiding effect can be realized by sheathing the guide rod outside the guide rod.

In one of the embodiments, the sealing cover is installed on the guide bracket and has a working state position and a sealing state position. When the sealing cover is in the working state position, the sealing cover and the liquid storage turntable They can be rotated relative to each other. When the sealing cover is in the sealing position, the sealing cover is snap-fitted with the liquid storage turntable and seals the liquid tank. At least two liquid-taking The position of the liquid-taking hole corresponds to the position of the pipetting head and the position of the sample inlet respectively. It can be understood that when the sample is subjected to pre-processing steps such as pipetting in the cartridge, the pipetting head or external mechanism can take samples and add samples through the liquid-taking hole; and when the sample completes the pre-processing steps, The purpose of sealing the liquid tank can be realized by rotating the liquid storage turntable to displace the liquid tank and the liquid taking hole and fix them with snap fit.

In one of the embodiments, the detection reagent cartridge further includes a sample tube, and the sample tube includes a snap-fit cap and a tube body, and the tube body is fixed in the hole of the sample tube through a snap connection, so that A sealing top cover is provided on the sealing cover, and the tube cover is detachably connected to the sealing top cover through tight fit. The sample tube is used to contain the pre-treated sample, and the tube cover and tube body can be snapped together to transfer the sample to the tube body after the pre-treatment is completed, and the tube cover is fastened to the tube by the sealing top cover. body, and then transfer the sealed sample tube to other equipment to complete the test. At this point, the sample tube is separated from the cartridge, and both are sealed after separation.

In this case, the sample tube is a PCR reaction tube, and subsequent amplification and detection items are required. After the PCR reaction tube is separated, the amplification and fluorescence detection can be realized on the qPCR instrument, and the real-time fluorescent quantitative PCR instrument (qPCR) can detect multiple samples at the same time. Time (1 sample and 1 item corresponds to 1 PCR reaction tube), and the volume is small. It avoids the defects that the PCR reaction tubes are not separated from the cartridges, and are directly loaded into the qPCR instrument. There is a mismatch with the instrument, inaccurate test results, and a large space occupation, which is not conducive to multi-sample detection.

At the same time, the number of sample tubes is not limited, and the number can be n, that is, the joint inspection of one sample corresponding to n detection items is realized.

In one of the embodiments, a groove is provided on the outer wall of the tube, and a tube body sealing ring is provided in the groove, and the tube body is dynamically sealed with the liquid storage turntable.

In one embodiment, the detection reagent cartridge further includes a tube cover pushing mechanism, and the tube cover pushing mechanism is fixed on the inner wall of the box and protrudes toward the liquid storage turntable. The sealing top cover provided on the sealing cover can be pushed by the pushing mechanism, and then the tube cover and the tube body can be buckled and fixed, so as to realize the sealing of the tube cover and the tube body.

The present invention also discloses a pre-processing device for sample detection, including the above-mentioned detection reagent cartridge, and a driving device, the driving device includes a lifting device and a rotating device, and the rotating device drives the liquid storage turntable along its rotation axis Rotate, the lifting device drives the liquid storage turntable to lift.

The above-mentioned pre-processing equipment for sample detection uses a lifting device and a rotating device to drive the liquid storage carousel to realize lifting and rotating, so as to complete the liquid transfer and promote the sample to undergo a pre-treatment reaction.

In one of the embodiments, the lifting device includes a push rod and a push rod driver, one end of the push rod is installed on the push rod driver, and the other end is against the liquid storage turntable, driven by the push rod driver The push rod shrinks or extends to drive the liquid storage turntable to move up and down; the rotation device includes a central axis of the liquid storage turntable and a driving device for driving the central axis to rotate. For example, the central shaft can be clamped and rotated by an external device to drive the liquid storage turntable to perform circular motion.

In one of the embodiments, the pre-processing equipment for sample detection also includes a pipetting drive device, the pipette is provided with a piston rod and an elastic piston, and the elastic piston is provided with a rod tightly fitted with the piston rod hole, and the pipetting drive device is a grasping device for driving the movement of the piston rod.

In one of the embodiments, the pre-processing equipment for sample detection also includes an incubation vibration device, a magnetic suction device and a moving mechanism, the liquid tank includes a reagent tank, a reaction tank and a waste liquid tank, and the incubation vibration device and the magnetic suction device All can approach or move away from the reaction tank driven by the moving mechanism. It can be understood that if the sample detection is a molecular diagnostic test, the pre-processing equipment includes an incubation and vibration device for nucleic acid extraction and purification, a magnetic suction device, etc., and the movement of the above-mentioned devices is realized by using a conventional moving mechanism. When incubating with shaking or magnetic suction, make the corresponding device close to or cover the corresponding liquid tank (such as the reaction tank) to complete the pretreatment work.

In one of the embodiments, the pre-processing device for sample detection further includes a mechanical gripper for grabbing the sample tube. It can be understood that the mechanical gripper adopts conventional mechanical elements, which can be set according to the usual settings in this field. However, through the design of the mechanical gripper and the sample tube, the pre-processing equipment can realize fully automatic operation and occupy a small space. , The advantages of high equipment flexibility.

The present invention also discloses a pre-processing method for sample detection, using the above-mentioned pre-processing equipment, including the following steps:

Adding samples: Open the cartridge cover, control the rotating device to drive the liquid storage turntable to rotate until the liquid tank is aligned with the sample inlet, add the sample to be processed and the reagent, and put the cartridge cover cover tightly;

Response: Control the rotating device to drive the liquid storage turntable to rotate, so that the position of the pipetting head corresponds to the position of the required liquid tank, and control the lifting device to drive the liquid storage turntable to rise, so that the pipetting head is at Corresponding to the liquid tank, control the pipetting device to absorb liquid, control the lifting device to lower the liquid storage turntable, control the liquid storage turntable to rotate to a predetermined position, complete the pipetting, and make the sample in the liquid tank Complete the pretreatment reaction within;

Sampling: control the pipetting device to suck out the pretreated sample solution, transfer it into a sample tube, and take out the sample tube.

Compared with the prior art, the present invention has the following beneficial effects:

A detection reagent cartridge of the present invention is equipped with a cartridge cover. After all the samples are added through the sample inlet, the cartridge can be tightly covered, and the subsequent sample pretreatment process is completed inside the cartridge, and the cartridge is sealed. , No pollution in the whole process. Moreover, the detection reagent cartridge mentioned above can cooperate with the rotation of the liquid storage turntable and the sample inlet, without the need for pre-packaged reagents inside the cartridge, which facilitates the adjustment of the cartridge for different detection items.

By adopting the method of rotating the liquid storage turntable, the axis of the liquid tank is aligned with the axis of the pipetting head, and the liquid tank and the pipetting head are distributed on the same rotation center of the cartridge. Compared with the way of translating the liquid pipetting head, Or the way of translating the liquid storage tray, the way of rotation is more space-saving, the storage space generated after the translation is moved, and the rotation does not require extra storage space, and the volume of the cartridge can be designed to be smaller and more space-saving.

Moreover, the manufacturing and assembly of the cartridge do not involve high-difficulty component equipment, which has the advantages of low manufacturing and assembly costs and independent controllable yield rate.

Description of drawings

Fig. 1 is a schematic diagram of the structure of the detection reagent cartridge;

Fig. 2 is the second schematic diagram of the structure of the detection reagent cartridge;

Figure 3 is a schematic exploded view of a partial structure of the detection reagent cartridge;

Figure 4 is a schematic diagram of the external structure of the detection reagent cartridge;

Fig. 5 is a structural schematic diagram of a liquid storage turntable;

Fig. 6 is a structural schematic diagram of a pipetting device and a guide rod;

Fig. 7 is a schematic diagram of the sample tube structure;

Figure 8 is a top view of the liquid storage carousel and the sample tube;

Fig. 9 is the EE sectional view of Fig. 8;

Figure 10 is a top view of the sealing cover;

Figure 11 is a sectional view of the sealing cover DD;

Fig. 12 is a schematic diagram of the movement direction of the liquid storage turntable in the detection reagent cartridge.

Among them: 100, liquid storage turntable; 110, reaction tank; 120, waste liquid tank; 131, first reagent tank; 132, second reagent tank; 133, third reagent tank; 134, fourth reagent tank; 141, first reagent tank One escape hole; 142, the second escape hole; 143, the third escape hole; 144, the fourth escape hole; 145, the fifth escape hole; 150, the sample tube hole; 200, the pipetting device; 211 , No. 1 pipetting head; 212, No. 2 pipetting head; 300, box body; 310, sample inlet; 320, cartridge cover; 330, jacking mechanism; 400, sample tube; 410, tube cover; 420, tube body; 421, pipe body sealing ring; 500, guide bracket; 510, turntable sealing ring; 520, elastic reset piece; 530, limit piece; 540, guide rod; 600, sealing cover; Guide sleeve; 630, sealing top cover.

Detailed ways

In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the associated drawings. Preferred embodiments of the invention are shown in the accompanying drawings. However, the present invention can be embodied in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the understanding of the disclosure of the present invention more thorough and comprehensive.

It should be noted that when an element is referred to as being “fixed” to another element, it can be directly on the other element or there can also be an intervening element. When an element is said to be "mounted" to another element, it can be directly mounted to the other element or intervening elements may also be present.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field of the invention. The terms used herein in the description of the present invention are for the purpose of describing specific embodiments only, and are not intended to limit the present invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

Example 1

A detection reagent cartridge, as shown in FIGS. 1-4 , includes: a liquid storage carousel 100 , a pipetting device 200 and a cartridge body 300 . And according to needs, it may be equipped with or not equipped with a special sample tube 400 , in this embodiment, the sample tube 400 is used as an example for illustration.

The liquid storage carousel 100 is provided with several liquid tanks for containing liquids and sample tube holes 150 for containing sample tubes 400, and the sample tube holes 150 and several samples of the liquid tanks surround the liquid storage The rotation axis of the turntable 100 is set. Specifically, several of the liquid tanks and the sample tube holes 150 form an annular arrangement around the axis of the liquid storage carousel 100, and the pipette head and the sample inlet 310 correspond to the positions of the annular rings respectively. .

In this embodiment, the liquid tanks include reagent tanks (the first reagent tank 131, the second reagent tank 132, the third reagent tank 133, and the fourth reagent tank 134), a reaction tank 110, and a waste liquid tank 120. It can be understood that for the setting of the number and function of various types of slots in a specific liquid tank, it can be set according to the requirements of specific testing items. For example, for testing items that generate more waste liquid, a larger waste liquid tank can be designed to avoid During the subsequent processing, if the sample needs to be shaken and other operations, the leakage or pollution will be caused. In this embodiment, the detection reagent cartridge further includes a guide bracket 500, the liquid storage turntable 100 is installed in the box body 300 through the guide bracket 500, and the turntable sealing ring 510 is sleeved on the guide bracket 500. The outer peripheral edge of the bracket 500 enables the guide bracket 500 to drive the liquid storage turntable 100 to form a dynamic seal with the box body 300 .

For limiting the downward movement of the liquid storage carousel 100 , the inner wall of the box body 300 is further provided with a limiting member 530 for limiting the downward movement of the liquid storage carousel 100 , and the limiting member 530 is arranged in the lower cavity. The stopper 530 is used to prevent the liquid storage carousel 100 from falling out of the box body 300 after excessive downward movement. It can be understood that the specific shape and position of the stopper 530 can be set according to conventional techniques in the art. , in this embodiment, the limiting member 530 is a limiting plate installed around the inner wall of the cartridge.

The liquid pipetting device 200 includes a piston pipette (such as a piston pipette similar in structure to a syringe) for sucking and discharging liquid, and the position of the pipetting head of the pipette corresponds to the position of the liquid tank. . It can be understood that the piston-type pipette can be equipped with equipment such as a syringe, and the accuracy requirement can be adjusted by controlling the diameter of the pipe, that is, the volume of the liquid that can be pipetted by the piston moving the same distance.

In this embodiment, there are two pipetting heads, and an escape hole is also provided on the liquid storage carousel 100. When one of the pipetting heads corresponds to the position of the liquid tank, the other of the pipetting heads The pipetting head corresponds to the position of the avoidance hole. It can be understood that since the liquid storage carousel 100 moves up, the position of the pipette head remains unchanged, so if there are two pipette heads, when one pipette head is used for pipetting and the other is idle, there will be no corresponding hole for the idle pipette head If it is placed in a different position, it will conflict with the surface of the liquid storage carousel 100, so the avoidance setting of the pipetting head needs to be considered. As for where to set the avoidance hole, those skilled in the art can set it according to the needs of the specific detection project process, as well as the number and position of the applicable pipetting head. The avoidance hole can be a specially designed hole position, or It can be other reagent tanks, etc. that do not affect the detection process.

According to the requirement that the detection item in this embodiment is molecular diagnosis, and the design of the two pipetting heads, as shown in Figure 5-6, the hole position on the liquid storage carousel 100 in this embodiment is set to accommodate the sample solution to be processed and Starting from the reaction tank 110 for the reaction, the reaction tank 110, the fourth avoidance hole 144, the waste liquid tank 120, the third avoidance hole 143, the fourth reagent tank 134, and the second reagent The tank 132 , the third reagent tank 133 , the first shelter hole 141 , the second shelter hole 142 , the sample tube hole 150 and the fifth shelter hole 145 .

The liquid storage turntable 100 is installed in the box body 300 through the guide bracket 500, and the inner space of the box body 300 is divided into an upper cavity above the surface of the liquid storage turntable 100 and a lower cavity below the surface of the liquid storage turntable 100 , the liquid storage turntable 100 can rotate and lift along the inner wall of the box body 300; the pipetting device 200 is fixed on the box body 300, and the pipetting head is located in the upper cavity, The liquid storage carousel 100 and the inner wall of the box body 300 make the upper cavity form a closed space; the box body 300 is provided with a sample inlet 310 communicating with the upper cavity and a card matching the sample inlet 310 Lid 320.

In order to further reduce the risk of contamination, the cartridge of this embodiment further includes a sealing cover 600 for sealing the liquid storage carousel 100, the sealing cover 600 is installed on the guide bracket 500, and the liquid storage carousel 100 can be Rotate relative to the sealing cover 600 . Through the use of the sealing cover, the liquid storage carousel can be sealed after the processing of the sample is completed, so as to realize the overall removal and further reduce the risk of contamination. Moreover, both the liquid storage turntable and the sealing cover are installed on the guide bracket, and they can rotate relative to each other without affecting the rotation of the liquid storage turntable.

In this embodiment, the detection reagent cartridge further includes an elastic reset member 520, one end of which is against the sealing cover 600, and the other end is against the upper inner wall of the box body. The downward force can be exerted indirectly on the liquid storage carousel 100 through the elastic return member 520 such as a spring, so as to realize the purpose of moving the liquid storage carousel downward and resetting after the liquid is taken by the pipetting device.

The upper inner wall of the box body is also provided with a guide rod 540 extending downwards for guiding the guide bracket 500, and the sealing cover 600 is provided with a guide sleeve 620 cooperating with the guide rod 540, and the guide rod 540 and the guide sleeve 620 are both arranged in the upper cavity. The guiding effect can be realized by sheathing the guide rod outside the guide rod. And the elastic return member 520 (spring) is also sleeved outside the guide sleeve 620 .

Specifically, the sealing cover 600 is installed on the guide bracket 500 and has a working state position and a sealing state position. When the sealing cover 600 is in the working state position, the sealing cover 600 and the liquid storage turntable 100 can be rotated relative to each other. When the sealing cover 600 is in the sealing state, the sealing cover 600 snap fits with the liquid storage turntable 100 and seals the liquid tank. The sealing cover 600 is provided with There are at least two liquid-taking holes 610 , the positions of the liquid-taking holes 610 correspond to the positions of the pipetting head and the sample inlet 310 respectively. It can be understood that when the sample is subjected to pre-processing steps such as pipetting in the cartridge, the pipetting head or external mechanism can take samples and add samples through the liquid-taking hole 610; and when the sample completes the pre-processing steps The purpose of sealing the liquid tank can be achieved by rotating the liquid storage turntable 100 to displace the liquid tank and the liquid taking hole 610 and fix them with snap fit.

The sample tube 400 in this embodiment includes a snap fit cap 410 and a tube body 420, as shown in Figures 7-11, the tube body 420 is fixed in the sample tube hole 150 through snap connections, The sealing cover 600 is provided with a sealing top cover 630 , and the tube cover 410 is detachably connected to the sealing top cover 630 through a tight fit.

The sample tube 400 is used to contain the pre-treated sample, and the tube cover 410 and tube body 420 can be snapped together to transfer the sample to the tube body 420 after the pre-treatment is completed, and the sealing cap 600 can be used to seal the sample tube 400. The sealed top cover 630 buckles the tube cover 410 on the tube body 420, and then transfers the sealed and buckled sample tube 400 to other equipment to complete the test. At this time, the sample tube 400 is separated from the cartridge, and both are sealed after separation.

Specifically, a groove is provided on the outer wall of the pipe body 420 , and a sealing ring of the pipe body 420 is provided in the groove, and the pipe body 420 is dynamically sealed with the liquid storage turntable 100 .

In order to fasten the tube cover 410 on the tube body 420, the detection reagent cartridge also includes a tube cover 410 push-in mechanism 330, and the tube cover 410 push-in mechanism 330 is fixed on the inner wall of the box body 300 and faces the The direction of the liquid storage turntable 100 protrudes. The sealing top cover 630 provided on the sealing cover 600 can be pushed by the pushing-in mechanism 330, and the tube cover 410 is snapped and fixed with the tube body 420 to realize the sealing of the tube cover 410 and the tube body 420. And then realize the fully automatic operation.

Example 2

A sample detection pretreatment device for molecular diagnosis, using the detection reagent cartridge and the driving device of the above-mentioned embodiment 1, the driving device includes a lifting device and a rotating device, and the rotating device drives the liquid storage carousel 100 along the The rotating shaft rotates, and the lifting device drives the liquid storage turntable 100 to lift up and down, as shown in FIG. 12 .

The above-mentioned sample detection pre-processing equipment uses a lifting device and a rotating device to drive the liquid storage carousel 100 to lift and rotate, so as to complete the pipetting and promote the sample to undergo a pre-treatment reaction.

Specifically, the lifting device includes a push rod and a push rod driver, one end of the push rod is installed on the push rod driver, and the other end is against the liquid storage turntable 100, and the push rod is driven by the push rod driver. The contraction or extension of the rod drives the liquid storage turntable 100 to move up and down; the rotation device includes a central axis of the liquid storage turntable 100 and a driving device for driving the central axis to rotate. For example, the central shaft can be clamped and rotated by an external device to drive the liquid storage turntable 100 to make a circular motion.

In order to realize the automatic operation process, the pre-processing equipment for sample detection also includes a pipetting drive device, the pipette is provided with a piston rod and an elastic piston, and the elastic piston is provided with a rod hole tightly fitted with the piston rod , the pipetting driving device is a grasping device for driving the movement of the piston rod.

For example, the piston rod is aligned with the center axis of pipette No. 1 in the cartridge, and goes down the axis until it reaches the bottom of the piston, at which point the top of the piston rod is tensioned to the surface of the piston (the piston is an elastic material) In the hole, the piston rod and the piston are integrated, and the piston rod is driven to move up and down to realize the pipetting of No. 1 pipette. The grasping device also grasps the piston rod of the No. 2 pipette so that the piston rod and the piston are integrated, and drives the grasping device to move up and down to realize the pipetting of the No. 2 pipette head 212 .

Since the pretreatment equipment of this embodiment is used for molecular diagnostic procedures, the sample detection pretreatment equipment also needs to extract and purify the nucleic acid of the sample, such as using magnetic beads for extraction and purification. Therefore, the equipment also includes an incubation and shaking device, a magnetic suction device And the moving mechanism, the incubation and vibration device and the magnetic suction device can be driven by the moving mechanism to approach or move away from the reaction tank 110 . It can be understood that if the sample detection is a molecular diagnostic test, the pre-processing equipment includes an incubation and vibration device for nucleic acid extraction and purification, a magnetic suction device, etc., and the movement of the above-mentioned devices is realized by using a conventional moving mechanism. When incubating with shaking or magnetic suction, make the corresponding device close to or cover the corresponding liquid tank (such as the reaction tank 110 ), so as to complete the pretreatment work.

Further, the pre-processing equipment for sample detection also includes a mechanical gripper for grabbing the sample tube 400 . It can be understood that the mechanical gripper adopts conventional mechanical elements, which can be set according to the usual settings in this field, but through the design of the mechanical gripper and the sample tube 400, the pre-processing equipment realizes fully automatic operation and occupies less space. The advantages of small size and high equipment flexibility.

Example 3

A method for pretreatment of molecular diagnostic test samples, using the pretreatment equipment of the above-mentioned embodiment 2, comprising the following steps:

1. Adding samples.

Open the cartridge cover 320, control the rotating device to drive the liquid storage turntable 100 to rotate until the liquid tank is aligned with the sample inlet 310, add the sample to be processed and the reagent, and put the cartridge cover 320 cap tightly. In this embodiment, the details are as follows:

1. The external mechanism drives to unscrew the cartridge cover 320;

2. At this time, the reaction tank 110 on the liquid storage carousel 100 is aligned with the axis of the sample inlet 310, and the pipette gun of the automatic instrument outside the cartridge is sequentially added with 300uL of RNA capture solution, 20uL of proteinase K, and 15uL of magnetic bead suspension;

3. Rotate the liquid storage turntable 100, at this time the second reagent tank 132 is aligned with the axis of the sample inlet 310, and add 500uL of rinse solution PWC at one time to the pipette gun of the automatic instrument outside the cartridge;

4. Rotate the liquid storage turntable 100, at this time the third reagent tank 133 is aligned with the axis of the sample inlet 310, and add 1000uL of rinse solution PWE at one time to the pipetting gun of the automatic instrument outside the cartridge;

5. Rotate the liquid storage turntable 100. At this time, the axis of the fourth reagent tank 134 is aligned with the sample inlet 310. Add 200 uL of RNase-free double-distilled water to the pipette gun of the external automation instrument of the cartridge at one time.

6. Rotate the liquid storage turntable 100. At this time, the axis of the reaction tank 110 is aligned with the sample inlet 310, and the external mechanism adds 200 uL of sample (the process of adding the sample needs to be carried out in a closed environment equipped with high-efficiency filtration of the instrument);

7. The external mechanism screws on the cartridge cover 320, and the entire cartridge is completely sealed.

Second, the pretreatment reaction.

Control the rotating device to drive the liquid storage turntable 100 to rotate, so that the position of the pipetting head corresponds to the position of the required liquid tank, and control the lifting device to drive the liquid storage turntable 100 to rise, so that the pipetting head is located at Corresponding to the liquid tank, control the pipetting device 200 to absorb liquid, control the lifting device to lower the liquid storage turntable 100, and control the liquid storage turntable 100 to rotate to a predetermined position, as shown in Figure 11, complete pipetting , and make the sample complete the pretreatment reaction in the liquid tank. In this embodiment, the details are as follows:

1. After the sample is added to the reaction tank 110, the reaction tank 110 contains: sample + 300uL RNA capture solution + 20uL proteinase K + 15uL magnetic bead suspension;

2. Add an incubation and shaking device at the position of the reaction tank 110, incubate and shake the liquid in the reaction tank 110, complete the cracking of the sample, release the nucleic acid, and shake it up, so that the nucleic acid is adsorbed to the magnetic beads;

3. Add a magnetic ring to the position of the reaction tank 110, so that the magnetic beads adsorbed with nucleic acid are adsorbed to the side wall of the reaction tank 110; , and then push the liquid storage turntable 100 upward as a whole, push the needle tip of the No. 1 pipetting head 211 and the bottom of the reaction tank 110 to leave only a small gap, drive the piston of the No. 1 pipetting head 211 upward, and suck the reaction tank 110 waste liquid except the nucleic acid adsorbed on the side wall; (at this time, No. 2 pipetting head 212 is in the fourth avoidance hole 144 position);

5. The push rod is driven to shrink, and the spring against the guide bracket 500 pushes the liquid storage turntable 100 to go down as a whole until the liquid storage turntable 100 reaches the stopper 530 of the liquid storage turntable 100, and the downward reset of the liquid storage turntable 100 is completed;

6. Rotate the liquid storage turntable 100 to align the axis of the waste liquid tank 120 with the No. 1 pipetting head 211, and then push the liquid storage carousel 100 upwards as a whole to push the needle tip of the No. 1 pipetting head 211 and the hole of the waste liquid tank 120 At the position where there is a gap at the bottom, drive the piston of No. 1 pipetting head 211 downward to discharge the waste liquid in No. 1 pipetting head 211 to the waste liquid tank 120; drive the push rod to shrink and push against the spring of the guide bracket 500 The liquid storage carousel 100 goes down as a whole until the liquid storage carousel 100 reaches the stopper 530 of the liquid storage carousel 100, and the downward reset of the liquid storage carousel 100 is completed; #The hole is filled with double distilled water, which will not affect the cleanliness of No. 2 pipetting head 212)

7. Similar to steps 4 and 5, rotate the liquid storage turntable 100 to align the axis of the second reagent tank 132 with the No. 1 pipetting head 211, and absorb 500 uL of rinse solution PWC; (at this time, the No. 2 pipetting head 212 is in the first Avoidance hole 141)

8. Similar to step 6, turn the liquid storage turntable 100 to align the axis of the reaction tank 110 with the No. 1 pipetting head 211, and discharge the PWC in the No. 1 pipetting head 211 to the reaction tank 110; (at this time, the No. 2 pipetting head 212 In the fourth avoidance hole 144); after driving the shock incubation and magnetic suction, absorb the waste liquid, make the waste liquid tank 120 and the No. 1 pipetting head 211 axis aligned, and discharge the waste liquid in the No. 1 pipetting head 211 to the waste liquid Groove 120; (at this time No. 2 pipetting head 212 is in the fourth reagent tank 134 position, and what the fourth reagent tank 134 is equipped with is double distilled water, which will not affect the cleanliness of No. 2 pipetting head 212); drive the push rod to shrink , against the spring of the guide bracket 500 to push the liquid storage turntable 100 to go down as a whole, until the liquid storage turntable 100 reaches the stopper 530 of the liquid storage turntable 100, and completes the downward reset of the liquid storage turntable 100;

9. Similar to step 7, turn the liquid storage turntable 100 to align the 3# hole with the axis of the No. 1 pipette head 211, and absorb 500uL of rinse solution PWE; (At this time, the No. 2 pipette head 212 is in the second avoidance hole 142 );

10. Repeat step 8; move the rinsed PWE to the waste liquid tank 120;

11. Repeat steps 9 and 10;

12. Similar to step 7, turn the liquid storage turntable 100 to align the axis of the fourth reagent tank 134 with the No. 1 pipette head 211, and pipette 100 uL of RNase-free double-distilled water to the 1# reaction well; (at this time, the No. 2 pipette The liquid head 212 is in the third pipetting tank, because the third pipetting tank position has been vacant after being sucked in steps 9, 10, and 11, which will not affect the cleanliness of the No. 2 pipetting head 212);

13. Repeat step 8; move the RNase-free double distilled water to the waste liquid tank 120;

14. Similar to step 7, turn the liquid storage turntable 100 to align the axis of the fourth reagent tank 134 with the No. 1 pipetting head 211, and pipette 100uL of RNase-free double-distilled water to the reaction tank 110; dissolve the nucleic acid in the double-distilled water Inside, drive to oscillate and mix evenly, and the liquid storage turntable 100 is reset.

15. Add a magnetic ring at the position of the reaction tank 110, so that the magnetic beads are adsorbed to the side wall of the reaction tank 110;

16. Similar to step 7, turn the liquid storage turntable 100 to align the axis of the reaction tank 110 with the No. 2 pipette head 212, and draw 5uL of purified nucleic acid (maintain the magnetic state); (At this time, the No. 1 pipette head 211 is in the Five escape holes 145)

17. Similar to step 8, rotate the liquid storage carousel 100 to align the axis of the sample tube hole 150 with the No. 2 pipette head 212, and discharge the nucleic acid in the No. 2 pipette head 212 to the sample tube 400 in the sample tube hole 150; (here Pipette head 211 of No. 1 is in the avoidance position 2 holes)

18. Complete the transfer of the pure nucleic acid to the sample tube 400 (the reaction tube is equipped with a PCR reaction solution).

Three, sampling.

Control the pipetting device 200 to suck out the pretreated sample solution, transfer it into the sample tube 400, and take out the sample tube 400, as shown in FIG. 12 . Specifically as follows:

1. Rotate the liquid storage carousel 100 to align the sample tube hole 150 with the axis of the jacking mechanism 330, push the liquid storage carousel 100 upward as a whole, and at the same time, control the mechanical gripper to grab the tube body 420 of the sample tube 400 (PCR reaction tube), follow the liquid storage carousel 100 to push up, in unison, push the liquid storage carousel 100 to be covered by the sealing cover 600 on the liquid storage carousel 100 turntable, at this time, the liquid storage carousel 100 is at the height position of the vertical direction It is higher than the position when absorbing liquid; continue to push upwards, and push the tube cover 410 to cover the tube body 420 (ie, the PCR reaction tube) to complete the sealing of the PCR tube; continue to push the liquid storage turntable 100 upwards, but grab the sample The mechanical gripper of the tube 400 no longer follows the liquid storage turntable 100 upwards. At this time, the sample tube 400 has been covered with a cover, and the sample tube 400 is separated from the cartridge body. The inside of the cartridge is still a closed structure, and the PCR tube is also a complete Closed structure, the seal of both.

2. The external drive grabs the cartridge body and discards it;

3. The mechanical gripper grabs the sample tube 400 (PCR reaction tube) and puts it on the qPCR instrument for amplification detection, thus completing PCR extraction, amplification, and detection.

The pretreatment process of the above-mentioned molecular diagnostic test samples is a fully sealed process, and the realization of sealing includes two steps of sealing. 1. Nucleic acid extraction and system construction are completed inside the cartridge during the entire liquid transfer process to achieve sealing; 2. PCR After the reaction tube is separated from the cartridge, the interior of the cartridge is still a closed structure, and the PCR tube is also a fully closed structure to achieve sealing.

The technical features of the above-mentioned embodiments can be combined arbitrarily. To make the description concise, all possible combinations of the technical features in the above-mentioned embodiments are not described. However, as long as there is no contradiction in the combination of these technical features, should be considered as within the scope of this specification.

The above-mentioned embodiments only express several implementation modes of the present invention, and the descriptions thereof are relatively specific and detailed, but should not be construed as limiting the patent scope of the invention. It should be pointed out that those skilled in the art can make several modifications and improvements without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention should be based on the appended claims.

Claims (20)

1. A test reagent cartridge, comprising:

the liquid storage turntable is provided with a plurality of liquid grooves for containing liquid and sample tube holes for containing sample tubes, and the sample tube holes and the plurality of liquid grooves are arranged around a rotating shaft of the liquid storage turntable;

the liquid transfer device comprises a liquid transfer device for sucking and discharging liquid, and the position of a liquid transfer head of the liquid transfer device corresponds to the position of the liquid groove; and

the liquid storage rotary table is arranged in the box body, the inner space of the box body is divided into an upper cavity above the surface of the liquid storage rotary table and a lower cavity below the surface of the liquid storage rotary table, and the liquid storage rotary table can rotate and lift along the inner wall of the box body; the liquid transfer device is fixed on the box body, the liquid transfer head is positioned in the upper cavity, and the liquid storage turntable and the inner wall of the box body form a closed space for the upper cavity; the box body is provided with a sample inlet communicated with the upper cavity and a card box cover matched with the sample inlet.

2. The assay reagent cartridge of claim 1, wherein the liquid reservoir comprises a reagent reservoir, a reaction reservoir, a waste reservoir.

3. The assay reagent cartridge of claim 1, wherein the plurality of fluid wells and the sample tube apertures are arranged in a circular ring around the axis of the reservoir carousel, and the pipetting head and the sample inlet both correspond to the circular ring.

4. A test reagent cartridge according to claim 1, wherein the pipette is a piston-type pipette.

5. The detection reagent cartridge of claim 4, wherein the number of the pipetting heads is two, the liquid storage turntable is further provided with a position avoiding hole, and when one pipetting head corresponds to the position of the liquid groove, the other pipetting head corresponds to the position avoiding hole.

6. The detection reagent cartridge of claim 1, wherein the inner wall of the cartridge body is further provided with a limiting member for limiting the downward movement of the liquid storage turntable, and the limiting member is disposed in the lower chamber.

7. The assay reagent cartridge of claim 1, wherein a rotary seal is disposed between the reservoir rotary disk and the inner wall of the cartridge body, and the reservoir rotary disk forms a dynamic seal with the cartridge body.

8. The assay reagent cartridge of claim 7, further comprising a guide bracket, wherein the reservoir carousel is mounted within the cartridge body via the guide bracket, and the carousel sealing ring is disposed around a peripheral edge of the guide bracket.

9. The assay reagent cartridge of claim 8, further comprising a sealing cap for sealing the reservoir disk, the sealing cap being mounted on the guide support, the reservoir disk being rotatable relative to the sealing cap.

10. The detector reagent cartridge of claim 9 further comprising an elastic reset member, wherein one end of the elastic reset member abuts against the sealing cover, the other end of the elastic reset member abuts against the inner wall of the cartridge body, and the elastic reset member is located in the upper chamber.

11. The detection reagent cartridge of claim 10, wherein the inner wall of the cartridge body is further provided with a guide rod for guiding the guide bracket, the sealing cover is provided with a guide sleeve matched with the guide rod, and the guide rod and the guide sleeve are both arranged in the upper chamber.

12. The test reagent cartridge of claim 9, wherein the sealing cover is mounted on the guide frame and has an operating position and a sealing position, wherein the sealing cover is rotatable relative to the reservoir turntable when the sealing cover is in the operating position, wherein the sealing cover is snap-fitted to the reservoir turntable and seals the liquid tank when the sealing cover is in the sealing position, and wherein the sealing cover has at least two liquid dispensing holes at positions corresponding to the liquid dispensing head and the sample inlet, respectively.

13. The assay reagent cartridge of claim 9, further comprising a sample tube, wherein the sample tube comprises a tube cover and a tube body which are in snap fit, the tube body is fixed in the sample tube hole through snap fit connection, the sealing cover is provided with a sealing top cover, and the tube cover is detachably connected with the sealing top cover through tight fit.

14. The test reagent cartridge of claim 13, wherein the outer wall of the tube has a groove, and a tube seal is disposed in the groove and the tube is in fluid-tight contact with the reservoir disk.

15. The detector reagent cartridge of claim 13 further comprising a cap insertion mechanism fixed to the inner wall of the cartridge body and protruding toward the reservoir disk.

16. A sample pretreatment apparatus, comprising the detection reagent cartridge according to any one of claims 1 to 15, and a driving device, wherein the driving device comprises a lifting device and a rotating device, the rotating device drives the liquid storage disk to rotate along a rotating shaft thereof, and the lifting device drives the liquid storage disk to lift.

17. The pretreatment equipment for sample detection according to claim 16, wherein the lifting device comprises a push rod and a push rod driver, one end of the push rod is mounted on the push rod driver, the other end of the push rod abuts against the liquid storage turntable, and the push rod is driven by the push rod driver to contract or extend to drive the liquid storage turntable to move up and down; the rotating device comprises a central shaft of the liquid storage turntable and a driving device for driving the central shaft to rotate.

18. The pretreatment equipment for sample detection according to claim 16, further comprising a liquid transfer driving device, wherein the liquid transfer device is provided with a piston rod and an elastic piston, the elastic piston is provided with a rod hole tightly matched with the piston rod, and the liquid transfer driving device is a gripping device for driving the piston rod to move.

19. The pretreatment apparatus before sample detection according to claim 16, further comprising an incubation oscillating device, a magnetic attracting device, and a moving mechanism, wherein the liquid tank comprises a reagent tank, a reaction tank, and a waste liquid tank, and both the incubation oscillating device and the magnetic attracting device can be driven by the moving mechanism to move close to or away from the reaction tank.

20. The pre-test treatment apparatus of claim 16, further comprising a mechanical gripper for gripping the sample tube.

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