CN116036940A

CN116036940A - Chip mixing device and sequencer

Info

Publication number: CN116036940A
Application number: CN202211686144.8A
Authority: CN
Inventors: 汪明月; 李晓峰; 翟文平
Original assignee: Guangdong Saikulaite Biological Co ltd
Current assignee: Fapon Biotech Inc; Guangdong Runpon Bioscience Co Ltd
Priority date: 2022-12-27
Filing date: 2022-12-27
Publication date: 2023-05-02

Abstract

The invention provides a chip mixing device and a sequencer. Wherein, chip mixing device includes: a base; the shaking mechanism is movably arranged on the base, and the chip is borne on the shaking mechanism; the liquid inlet module is used for placing a liquid inlet end of the chip and is provided with a liquid inlet channel in butt joint fit with a liquid inlet of the chip; the liquid outlet module is used for placing a liquid outlet end of the chip, and is provided with a liquid outlet channel in butt joint fit with a liquid outlet of the chip, and the shaking mechanism drives one end of the chip to rise and/or drives the other end of the chip to fall so as to mix the reagents in the chip. The invention solves the problem that the risk of damaging the detection chip and the sample exists in the prior art due to the loading and mixing mode of the sequencer.

Description

Chip mixing device and sequencer

Technical Field

The invention relates to the technical field of gene sequencers, in particular to a chip mixing device and a sequencer.

Background

In a conventional gene sequencer, a sample and/or a reagent is loaded and mixed in a mode of loading and mixing by using an external pressure driving device (i.e. a pump, a valve, a pipeline, etc.), sucking and pushing and mixing, and the sample and/or the reagent is added into a sample reaction area from a reagent bin and sucked and pushing and mixing are performed, for example, a sequencing chip of the gene sequencer. The reagent loading and mixing system is complex, the reliability is low, and in the pressure control process of the system, the pressure is controlled to damage the detection chip and the sample.

Disclosure of Invention

The invention mainly aims to provide a chip mixing device and a sequencer, which are used for solving the problem that the risk of damaging a detection chip and a sample exists in a loading mixing mode of the sequencer in the prior art, reducing the consumption of reagents and realizing the repeated use of the reagents.

In order to achieve the above object, the present invention provides a chip blending device, including: a base; the shaking mechanism is movably arranged on the base, and the chip is borne on the shaking mechanism; the liquid inlet module is used for placing a liquid inlet end of the chip and is provided with a liquid inlet channel in butt joint fit with a liquid inlet of the chip; the liquid outlet module is used for placing a liquid outlet end of the chip, and is provided with a liquid outlet channel in butt joint fit with a liquid outlet of the chip, and the shaking mechanism drives the chip to carry out at least one of lifting one end of the chip, lowering the other end of the chip and swinging in a plane where the chip is located so as to mix reagents in the chip.

Further, shake even mechanism includes: the platform, the chip, the liquid inlet module and the liquid outlet module are arranged on the platform; the driving piece is in driving connection with the platform and drives the platform to swing; and/or the platform is rotatably connected with the base through the adapter, the driving piece is in driving connection with the adapter, and the platform is driven to swing through the driving adapter.

Further, the driving piece comprises a lifting mechanism, and the lifting mechanism is connected with the platform and drives the platform to swing; and/or the platform is rotatably connected with the base through the adapter, the adapter comprises at least one of a ball head and a rotating shaft, and when the adapter comprises the rotating shaft, the axis of the rotating shaft is arranged non-perpendicularly to the surface of the chip.

Further, the platform is rotatably connected with the base through the adapter, the adapter comprises a rotating shaft, the axis of the rotating shaft is parallel to the surface of the chip and perpendicular to the length direction of the chip, and the axis of the rotating shaft is located under the central line of the length direction of the chip.

Further, the shaking mechanism further comprises a reset piece, and the reset piece is connected with the platform and drives the platform to swing to a preset balance position.

Further, the maximum angle formed between the shaking mechanism and the horizontal plane when the shaking mechanism swings is 45 degrees.

Further, the chip mixing device further comprises: a waste liquid module; and the electromagnetic valve module is connected with the liquid outlet, the liquid outlet module and the waste liquid module and controls the communication relationship among the liquid outlet, the liquid outlet module and the waste liquid module.

Further, the waste liquid module comprises a waste liquid busbar, a pump body and a waste liquid barrel which are sequentially communicated, wherein the waste liquid busbar is communicated with the electromagnetic valve module, and the pump body provides power for the extraction of liquid in the liquid outlet module.

Further, the shaking mechanism comprises a platform, the platform is provided with a plurality of mounting positions for receiving chips, and each mounting position is arranged in an array mode and/or an annular mode.

Further, the chip mixing device further comprises: a kit having a plurality of receiving chambers for storing reagents; and the first ends of the communication pipelines are matched with the accommodating cavities, and the positions of the first ends and/or the reagent boxes are adjustably arranged so that the communication pipelines are matched with different accommodating cavities.

Further, the kit is a rotary disc type kit, and each accommodating cavity is rotatably arranged along the circumferential direction of the kit so as to change the accommodating cavity matched with the first end of the communication pipeline.

Further, each accommodating cavity is arranged in a linear manner, and the kit is movably arranged along the linear manner so as to change the accommodating cavity matched with the first end of the communication pipeline.

Further, shake even mechanism and include the platform, the platform has a plurality of installation positions that are used for accepting the chip, and each installation position is rotationally set up along the circumference of kit, and the communication pipeline extends along the radial of kit to change the cooperation relation between each accommodation chamber and each installation position.

Further, the shaking mechanism is provided with a connecting structure for fixing the chip on the shaking mechanism, and the connecting structure comprises at least one of an electromagnetic adsorption structure and a negative pressure adsorption structure.

According to another aspect of the present invention, there is provided a sequencer including the above-mentioned chip mixing device, the chip mixing device having an initial state and a mixing state, when the chip mixing device is in the initial state, a chip carried by the chip mixing device and the signal acquisition device being maintained at a preset relative position, and when the chip mixing device is in the mixing state, the chip mixing device moving and mixing reagents in the chip.

Further, the sequencer further comprises a detection device electrically connected with the acquisition device and used for detecting the position of the chip, and the detection device is used for determining that the chip is located at a preset relative position in an initial state.

By adopting the technical scheme of the invention, the sample adding of the chip is realized by arranging the liquid inlet module and the liquid outlet module which are matched with the chip, and meanwhile, the shaking mechanism is also arranged, so that the shaking is realized. Specifically, the liquid inlet module and the liquid outlet module are respectively in butt joint with the liquid inlet and the liquid outlet of the chip, so that when sample addition is needed, reagents are only needed to be added into the liquid inlet module, the reagents can enter the reaction area of the chip through the liquid inlet module, and similarly, the reagents in the chip can be discharged only through the liquid outlet module when liquid is discharged. And after the sample is added, the shaking mechanism acts, and the shaking mechanism can drive the liquid inlet module, the liquid outlet module and the chip on the shaking mechanism to integrally swing, so that the reagent added into the chip is uniformly shaken by utilizing the action of gravity. The setting mode can realize the loading function of the sample and the reagent, simultaneously realize the mixing of the reagent and the sample in the chip reaction area, does not need the operations such as pressurization, and can not damage the chip and the like due to improper pressure control, and the sample adding and mixing process is simple, stable and reliable. And the structure is simple, the method is stable and reliable, the reagent is repeatedly used, the reagent waste is reduced, and the cost is reduced.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention. In the drawings:

fig. 1 shows a schematic layout of a chip blending device of the present invention;

fig. 2 is a schematic diagram showing the structure of the chip mixing device in fig. 1 when swinging in one direction;

fig. 3 is a schematic view showing the structure of the chip mixing device in fig. 1 when swinging in the other direction;

fig. 4 is a schematic structural view of the chip blending device according to the present invention in the first mode of arrangement;

fig. 5 shows a schematic structural diagram of the chip blending device according to the present invention in the second mode of arrangement;

fig. 6 shows a schematic structural diagram of the chip blending device according to the present invention in the third mode of arrangement;

fig. 7 shows a schematic structural diagram of the chip mixing device in fig. 1.

Wherein the above figures include the following reference numerals:

10. a liquid inlet module; 11. a liquid inlet channel; 20. a liquid outlet module; 21. a liquid outlet channel; 30. a chip; 31. a liquid inlet; 32. a liquid outlet; 40. a waste liquid module; 41. a waste liquid busbar; 42. a pump body; 43. a waste liquid barrel; 50. a solenoid valve module; 60. a kit; 70. a mounting position; 80. a first end; 90. a guide rail; 100. a base; 110. a shaking mechanism; 120. an adapter; 130. a rest position.

Detailed Description

It should be noted that, in the case of no conflict, the embodiments and features in the embodiments may be combined with each other. The invention will be described in detail below with reference to the drawings in connection with embodiments.

It is noted that all 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 otherwise indicated.

In the present invention, unless otherwise indicated, terms of orientation such as "upper, lower, top, bottom" are used generally with respect to the orientation shown in the drawings or with respect to the component itself in the vertical, upright or gravitational direction; also, for ease of understanding and description, "inner and outer" refers to inner and outer relative to the profile of each component itself, but the above-mentioned orientation terms are not intended to limit the present invention.

In the prior art, the problem of risk of damaging a detection chip and a sample exists due to a sequencer loading and mixing mode, bubbles are easily generated in a pipeline due to repeated sucking and pushing operation, the cost of parts such as a high-precision injection pump, a rotary valve and the like is high, the consumption of the sample and the reagent is high due to the fact that a pump valve pipeline loads the reagent, and the detection cost is increased.

In order to solve at least part of the problems, the invention provides a chip mixing device and a sequencer.

The chip mixing device as shown in fig. 1 and 7 comprises a base 100, a shaking mechanism 110, a liquid inlet module 10 and a liquid outlet module 20, wherein the shaking mechanism 110 is movably arranged on the base 100, and the chip 30 is borne on the shaking mechanism 110; the liquid inlet module 10 is used for placing a liquid inlet end of the chip 30, and the liquid inlet module 10 is provided with a liquid inlet channel 11 in butt joint fit with a liquid inlet 31 of the chip 30; the liquid outlet module 20 is used for placing a liquid outlet end of the chip 30, the liquid outlet module 20 is provided with a liquid outlet channel 21 in butt joint with a liquid outlet 32 of the chip 30, and the shaking mechanism 110 drives the chip 30 to perform at least one of lifting one end of the chip 30, lowering the other end of the chip 30, and swinging in a plane of the chip 30 so as to mix the reagents in the chip 30.

In this embodiment, through being provided with both the liquid inlet module 10 and the liquid outlet module 20 and the cooperation of chip 30, realize the application of sample of chip 30, still be provided with simultaneously and shake even mechanism 110, realize shaking even. Specifically, the liquid inlet module 10 and the liquid outlet module 20 are respectively in butt joint with the liquid inlet 31 and the liquid outlet 32 of the chip 30, so that when sample addition is needed, reagents are only needed to be added into the liquid inlet module 10, the reagents can enter the reaction area of the chip 30 through the liquid inlet module 10, and similarly, the reagents in the chip 30 can be discharged through the liquid outlet module 20 when liquid is discharged. After the sample is added, the shaking-up mechanism 110 acts, and the shaking-up mechanism 110 can drive the liquid inlet module 10, the liquid outlet module 20 and the chip 30 to integrally swing, so that the reagent added into the chip 30 is shaken up by repeated movement for multiple times under the action of gravity. The above arrangement mode can realize the loading function of the sample and the reagent, simultaneously realize the mixing of the reagent and the sample in the reaction area of the chip 30, does not need the operations such as pressurization, and can not damage the chip 30 due to improper pressure control, and the like, and the sample adding and mixing process is simple, stable and reliable. And the structure is simple, the method is stable and reliable, the reagent is repeatedly used, the reagent waste is reduced, and the cost is reduced.

The chip mixing device of this embodiment more precisely mixes the reagents contained in the chip 30. The reagent according to the present embodiment is generally referred to as a reagent as long as it is a sample or a reagent contained in the chip 30 and is uniformly mixed in the chip 30.

It should be noted that, the shaking-up mechanism 110 drives the liquid inlet module 10, the liquid outlet module 20 and the chip 30 to swing integrally, that is, one side is raised and the other side is lowered, then the raised side is lowered, the lowered side is raised, and the shaking-up is performed in a repeated manner, as shown in fig. 2 and 3, the mixing effect is better, and the reagent can be prevented from overflowing from the liquid inlet module 10 and the liquid outlet module 20. Or the reagent in the reaction area of the chip 30 can be uniformly mixed by lifting the liquid inlet module 10, for example, the shaking mechanism 110 only controls the lifting of the liquid inlet module 10 at one side, the height of the liquid outlet module 20 at one side is basically unchanged.

It should be noted that the swing amplitude should be noted during the swing process, so as to avoid the reagent overflowing from the liquid inlet module 10 or the liquid outlet module 20. Preferably, the maximum angle formed between the shaking-up mechanism 110 and the horizontal plane when it swings in this embodiment is 45 °. Preferably 15 degrees, so that the mixing effect can be ensured and the reagent can be prevented from overflowing.

The liquid inlet module 10 and the liquid outlet module 20 of this embodiment adopt a block structure, and are provided with a plurality of longitudinal channels, namely, a liquid inlet channel 11 and a liquid outlet channel 21, for the liquid inlet module 10, the top of the liquid inlet channel 11 is an inlet, the bottom is an outlet, the outlet at the bottom is in butt joint with the liquid inlet 31 of the chip 30, and the structure of the liquid outlet module 20 is basically consistent with that of the liquid inlet module 10, except that the positions of the inlet and the outlet of the liquid outlet channel 21 are different. The specific number of channels on the liquid inlet module 10 and the liquid outlet module 20 may be set according to the specific structure of the chip 30, and the specific structure of the module is not limited to the above structure of the embodiment, and may be adjusted according to the needs.

In this embodiment, the shaking-up mechanism 110 includes a platform and a driving member, the platform plays a role of placing components, the liquid inlet module 10 and the liquid outlet module 20 are all placed on the platform, the chip 30 is placed on the liquid inlet module 10 and the liquid outlet module 20, so that the chip 30, the liquid inlet module 10 and the liquid outlet module 20 are all placed on the platform, and the shaking-up mechanism 110 can drive the liquid inlet module 10, the chip 30 and the liquid outlet module 20 to swing together, so as to realize mixing. The driving piece is matched with the platform in a driving way and can drive the platform to swing so as to drive the chips 30 on the platform to be uniformly mixed.

In this embodiment, the bottom of the platform has a connecting portion extending downward for a certain length, and an adaptor 120 is disposed between the connecting portion and the platform, and the two are connected by the adaptor 120. Specifically, the adaptor 120 of the present embodiment adopts a rotating shaft, the connecting portion is provided with a mounting hole, and correspondingly, the base 100 is also provided with a mounting hole, and the rotating shaft is inserted into the mounting holes of the two, so that the platform is rotatably connected with the base 100 through the rotating shaft. Of course, the adaptor 120 may have other structures such as a ball head instead of the rotation shaft, as long as the mixing of the reagents can be achieved by swinging or rotating the platform with respect to the base 100.

The driving piece can adopt parts such as motor, cylinder as required, can also include the driving medium etc. that the cooperation set up, and the driving piece can be direct be connected with the pivot drive, and for example the driving piece includes the motor, and the motor is direct or through parts such as gear drive and pivot drive cooperation, pivot for platform fixed connection, like this, the driving piece can be through the effect that drives platform swing through the rotation of drive pivot realization and shake even.

Besides the manner that the driving piece drives the platform to swing through the adaptor 120, the driving piece can also be directly matched with the platform, for example, the driving piece comprises a lifting mechanism, the lifting mechanism can adopt components such as an air cylinder, the air cylinder rod of the air cylinder is connected with the bottom surface of the liquid inlet module 10 or the liquid outlet module 20 opposite to the platform, the air cylinder rod can push one side of the platform to ascend and descend when the air cylinder acts, and just like the above-mentioned air cylinder can be arranged below the liquid inlet module 10 and the liquid outlet module 20, the air cylinder can be arranged at one position, and when the air cylinder is arranged, the air cylinders at two sides can simultaneously act and match to realize one-side ascending and one-side descending, at the moment, the rotating shaft and the platform do not need to be fixedly connected, and the air cylinder can also be replaced by a structural form of a motor and a telescopic rod.

Of course, the matching mode between the driving member and the platform is not limited to the above-mentioned mode in this embodiment, and other structural modes can be adopted as required, as long as the platform can be driven to swing to realize uniform mixing of the reagents.

When in actual use, the platform swings for preset times and preset time, and different times and times can be set according to the needs according to different conditions, such as different numbers of chips, the number of chip flow channels, the width of the chip flow channels, the types of reagents and the like, so that the actual mixing condition is matched with the demand condition, and the mixing effect is ensured.

As shown in fig. 2 and 3, the shaking mechanism 110 in this embodiment adopts a left-right swinging manner, that is, swings along the length direction of the chip 30, and raises and lowers both ends of the length of the chip 30 respectively, and based on this, the axis of the rotating shaft in this embodiment is parallel to the surface of the chip 30, and because the platform and the chip 30 are generally disposed transversely, the rotating shaft is also disposed transversely, and the axis of the rotating shaft is perpendicular to the length direction of the chip 30, so that the reagent can be uniformly swung along the length direction when the platform swings, and of course, the axis of the rotating shaft and the surface of the chip 30 do not need to be disposed in parallel, and only non-perpendicular arrangement is required. Preferably, the axis of the rotating shaft is located right below the center line in the middle of the length direction of the chip 30, so that the swing amplitudes of the platform in two directions are the same, the arrangement is convenient, and the mixing effect can be ensured. Of course, in addition to the above-described swinging in the direction, the chip 30 may be swung in the width direction, and the axis of the rotation shaft may be arranged in parallel with the longitudinal direction of the chip 30. Or the two modes can be combined, namely the rotating shaft can swing along the length and the width, two rotating shafts can be arranged at the moment, one of the two rotating shafts is arranged along the length direction, and the other rotating shaft is arranged along the width direction. Of course, other ways may be employed as desired and are not set forth herein.

Optionally, the shaking mechanism 110 further includes a reset member, where the reset member may be a torsion spring, or a spring, and when the torsion spring is adopted, the torsion spring is sleeved on the rotating shaft and is abutted to the rotating shaft, and the torsion spring applies a reset force to the rotating shaft, so that the rotating shaft drives the platform to swing to a predetermined balance position, that is, a horizontal position; when the spring is adopted, two ends of the spring can be respectively connected with the platform and the base 100, and the spring can directly provide a restoring force for the platform, so that the platform swings to a preset balance position under the action of the spring. Or the resetting piece is not required to be arranged, and the platform is driven to a preset balance position by the driving piece.

In this embodiment, the chip mixing device further includes a waste liquid module 40 and an electromagnetic valve module 50, where the waste liquid module 40 is used for recycling the tested reagent, and the electromagnetic valve module 50 is used for controlling the on-off relationship among the liquid outlet 32, the liquid outlet module 20 and the waste liquid module 40, specifically, the electromagnetic valve module 50 is connected with the liquid outlet 32, the liquid outlet module 20 and the waste liquid module 40, and the electromagnetic valve module 50 realizes recycling the waste liquid by controlling the communication relationship among the liquid outlet 32, the liquid outlet module 20 and the waste liquid module 40. The connection of the flow channels between the solenoid valve module 50, the waste liquid module 40 and the liquid outlet 32 may be selected from two types, namely, a pipe connection and an integrated manifold block. Wherein the integrated manifold block structure can reduce dead volume and reduce reagent residue.

Specifically, the electromagnetic valve module 50 includes three interfaces, which are a normal port, a normally closed port, and a normally open port, and in this embodiment, the normal port of the electromagnetic valve module 50 is communicated with the liquid outlet channel 21 of the liquid outlet module 20, the normally closed port is connected with the liquid outlet 32, and the normally open port is connected with the liquid waste module 40. Thus, the electromagnetic valve module 50 can be switched to the normally closed port when the sample is added and evenly mixed, the reagent flows into the liquid outlet channel 21 from the liquid outlet 32 through the electromagnetic valve module 50, and when the reagent is recovered, the electromagnetic valve module 50 is switched to the normally open port, the reagent in the liquid outlet channel 21 is discharged into the waste liquid module 40, and the primary reagent liquid inlet and the waste liquid are completed. Of course, the above structure may be realized by other structures, not limited to the solenoid valve module 50.

The waste liquid module 40 of this embodiment includes the waste liquid busbar 41, the pump body 42 and the waste liquid barrel 43 of intercommunication in order, and the waste liquid busbar 41 communicates with the normally open mouth of solenoid valve module 50, and the pump body 42 is the negative pressure pump, and it is located between waste liquid busbar 41 and the waste liquid barrel 43 to make the pump body 42 provide power for the extraction of the liquid in the liquid module 20, can retrieve the waste liquid in the liquid channel 21 to the waste liquid barrel 43 in the time of reagent is retrieved. The above-mentioned waste liquid module 40 not only can carry out the recovery of waste liquid, can also be used for the recovery of washing liquid when chip 30 washs, when wasing promptly, pour into the chip 30 with the washing liquid from feed liquor passageway 11 into, shake even mechanism 110 and sway for the washing liquid washs the reaction zone of chip 30, then discharges through solenoid valve module 50, drain channel 21, waste liquid busbar 41, pump body 42 and waste liquid bucket 43, accomplishes the washing.

The whole use process of the chip blending device of this embodiment is as follows:

when sample is introduced, initially, the chip 30 is horizontally positioned, the sample application gun head sucks the reagent from the reagent cartridge 60, moves to the liquid inlet module 10, pushes the reagent into the liquid inlet module 10, and then the sample application gun head is moved away. The shaking mechanism 110 moves to lift the liquid inlet 31 of the chip 30, the liquid outlet 32 lowers, as shown in fig. 2, the reagent spreads over the reaction area of the whole chip 30 through the liquid inlet 31 by using potential energy and self gravity, and then flows out through the liquid outlet 32, the electromagnetic valve module 50 is opened to be normally closed in advance in the reagent sample injection state, and the reagent flows into the liquid outlet module 20 through the liquid outlet 32, the electromagnetic valve module 50. After the reagent feeding is completed, the solenoid valve module 50 is opened to a normal opening, the negative pressure pump is opened, the reagent in the liquid outlet module 20 is discharged into the waste liquid barrel 43, and the primary reagent feeding and waste liquid discharging are completed.

When the reagent in the chip 30 needs to be uniformly mixed, initially, the chip 30 is horizontally positioned, the reagent is sucked out of the reagent box 60 by the sample adding gun head, moves to the liquid inlet module 10, pushes the reagent into the liquid inlet module 10, and then the sample adding gun head is moved away. The shaking mechanism 110 moves to lift the liquid inlet 31 of the chip 30, the liquid outlet 32 lowers, as shown in fig. 2, the reagent spreads over the whole chip 30 through the liquid inlet 31 by utilizing potential energy and self gravity, and then flows out through the liquid outlet 32, and in the state of uniformly mixing the reagent, the electromagnetic valve module 50 is opened to be normally closed in advance, and the reagent flows into the liquid outlet module 20 through the liquid outlet 32, the electromagnetic valve module 50. After the reagent is fed, the shaking-up mechanism 110 is controlled to lift the liquid outlet 32 and lower the liquid inlet 31, and as shown in fig. 3, the electromagnetic valve module 50 is kept open to be normally closed, so that the reagent flowing into the liquid outlet 32 module flows back into the liquid inlet module 10. The liquid inlet 31 or the liquid outlet 32 can be switched to move at high and low positions once, namely, a mixing operation is completed, the mixing times can be controlled according to actual needs, after the mixing is finished, the chip 30 is restored to the horizontal position, the reagent waste liquid is discharged, and the subsequent operation is the same as the sample injection flow.

When the cleaning operation is performed, general cleaning and deep cleaning may be selected. The general washing operation is the same as the sample injection process, except that the reaction reagent is replaced with a washing liquid. During deep cleaning operation, the chip 30 always keeps ready state, a large-volume sample-adding gun head is selected, the electromagnetic valve module 50 is opened to a normal opening in advance, the rotating speed of the negative pressure pump is controlled to a proper gear, and the negative pressure pump is powered on, and meanwhile, the sample-adding gun head pushes a large amount of cleaning liquid into the liquid-feeding module 10, and meanwhile, the negative pressure pump discharges waste liquid after cleaning into the waste liquid barrel 43. In the deep cleaning process, it is necessary to ensure that the liquid in the liquid inlet module 10 does not overflow.

In addition, the chip mixing device of the embodiment can also be applied to a sequencing process in a gene sequencer, in particular to a scheme that a reagent loading process and a photographing process of a chip are separated, at the moment, the process can be adjusted to chip reagent loading, shaking and returning, and then the chip 30 is moved to a photographing module position for photographing.

Alternatively, the platform may be configured as a large-sized platform, on which at least one mounting location 70 for receiving the chips 30 may be disposed, so that, considering that the number of chips 30 may be large in practical use, a plurality of mounting locations 70 are preferably disposed, where each mounting location 70 is arranged in an array and/or in a ring shape, and each mounting location 70 is provided with a set of liquid inlet modules 10, liquid outlet modules 20, and chips 30. Thus, the platform can simultaneously perform the mixing operation on the plurality of chips 30, thereby improving the mixing efficiency.

In practical use, the chip 30 may be used to manually inject reagents into the liquid inlet module 10 by using a sample injection gun head, or may be used in an automated manner. Specifically, the chip mixing device further includes a reagent kit 60 and a communication line for communicating the accommodating chamber and the chip 30, and the communication line of this embodiment is more precisely an ADP pipetting module (for example, the ZEUS series of Hamilton) which can move on a guide rail, stay, and load in accordance with a set position. The kit 60 has a plurality of accommodating chambers for accommodating reagents, so that different reagents can be respectively accommodated in the different accommodating chambers, the communicating pipelines play a role of communicating the accommodating chambers with the chips 30, the first ends 80 of the communicating pipelines are matched with the accommodating chambers, the communicating pipelines can extend as required, and only the second ends of the communicating pipelines are matched with the chips 30 on the mounting positions 70, so that the reagents in the accommodating chambers can be conveyed into the chips 30 through the communicating pipelines. At the same time, the first end 80 and/or the reagent cartridge 60 are adjustably positioned such that the first end 80 can be communicatively coupled to different receiving cavities to effect delivery of different reagents to the chip 30.

The specific arrangement of the kit 60 and the mounting site 70 is various according to the actual scene and the requirement, and the following three modes are listed:

mode one

As shown in fig. 4, each mounting position 70 in this mode is arranged in an array, and the reagent kit 60 is disc-shaped, and the reagent discs are all rotatably arranged, so as to form a turntable-type reagent kit 60, the reagent kit 60 has a plurality of accommodating cavities for accommodating reagents, and each accommodating cavity is arranged along the rotation circumference of the reagent kit 60, the first end 80 has a fixed sampling position, the sampling position is a substantially fixed position, the first end 80 is aligned with one accommodating cavity when being positioned at the sampling position, and when the added reagents need to be replaced, the reagent kit 60 rotates, so that the accommodating cavities rotate along the axial direction of the reagent kit 60, thereby changing the accommodating cavities positioned at the sampling position, and also changing the accommodating cavities matched with the communication pipeline, so that the communication pipeline can convey different reagents.

Meanwhile, the communicating pipeline between the reagent kit 60 and the mounting position 70 can adopt a mode of arranging the guide rails 90, the guide rails 90 can be a plurality of guide rails, can be straight lines or curved, and each guide rail 90 is connected to form a straight line or a folded line type movement path. The arrangement of the guide rail 90 is adapted to the arrangement of the mounting locations 70, and the mounting locations 70 may be arranged according to the need, for example, in a 2×3 array arrangement, and may be located at one side of the kit 60, where the guide rail 90 further has a plurality of docking locations 130 for docking the pipette tips and performing operations such as sample loading, liquid feeding, liquid suction, etc., where the docking locations have various designs, for example, are located at the liquid sampling locations of the respective holding compartments on the kit, and are located at each liquid inlet of the liquid inlet module of each mounting location 70, for example. Thus, after sampling is completed, reagents can be injected along the rails 90 into the chips 30 on the respective mounting sites 70, thereby performing the respective sampling. In addition to the sampling site, when a pipetting module is used, there are provided, for example, a pipetting gun head site and a discarding gun head site.

Mode two

As shown in fig. 5, the mounting positions 70 of the present embodiment are still arranged in an array, but the difference between the first embodiment and the first embodiment is that the kit 60 is in a strip shape, the kit 60 still has a plurality of accommodating cavities for accommodating reagents, but each accommodating cavity is arranged in a linear manner along the length direction of the kit 60, and the kit 60 can move axially, that is, in the linear direction along the length direction, so that the first end 80 of the communication pipeline can be matched with different accommodating cavities to achieve the same purpose. The arrangement of the guide rails 90 may be substantially the same as in the first mode, but the guide rails 90 located at the reagent boxes are not rotated by the reagent trays to butt against the respective accommodating chambers, but a plurality of stopping positions 130 are provided on the guide rails 90, each stopping position 130 corresponds to one accommodating chamber, so that the pipetting module can aspirate reagents from the respective accommodating chambers.

Mode three

As shown in fig. 6, the difference from the first embodiment is that the arrangement mode of the reagent kit 60 in the present embodiment is basically unchanged, and still is the rotatable reagent kit 60 and the accommodating cavity arranged along the circumferential direction of the reagent kit 60, but each mounting position 70 in the present embodiment is arranged along the circumferential direction of the reagent kit 60, and each mounting position 70 is also rotatably arranged along the circumferential direction of the reagent kit 60, specifically, the rotation of the mounting position 70 can be realized by the integral rotation of the platform. Meanwhile, the communication pipeline extends along the radial direction of the kit 60, and the first end 80 and the second end thereof can be respectively matched with the accommodating cavities and the mounting positions 70, so that the matching relationship between each accommodating cavity and each mounting position 70 is changed; in addition, the guide rail 90 for moving the pipetting module is also designed in this solution and is located at the accommodating cavity of the kit 60, and the docking station 130 is designed at each liquid inlet of the pipetting module of each mounting station 70, so that the pipetting gun head docks and performs operations such as sample adding, liquid sucking and the like. Thus, the first end 80 and the second end of the communication line have a fixed sample site and sample site, respectively, the fit between the sample site and the cartridge 60 is the same as in the first embodiment, and the fit between the sample site and the chip 30 on the mounting site 70 is substantially the same as the fit between the sample site and the cartridge 60. During sample loading, all the mounting positions 70 can integrally rotate, so that the chip 30 matched with the second end is changed, and the first end 80 can be injected into the corresponding chip 30 from the second end through the communication pipeline after the reagent is sucked from the corresponding accommodating cavity, so that sample loading is realized.

Of course, the specific layout of the kit 60 and the mounting site 70 is not limited to the three modes described in the present embodiment, and other arrangements may be adopted as required, as long as sampling and loading effects can be achieved. And there is no conflict among the three arrangement modes, and a plurality of the three arrangement modes can be adopted at the same time.

Optionally, the shaking-up mechanism 110 has a connection structure, where the connection structure is used to fix the chip 30 on the shaking-up mechanism 110, and the specific structure and the fixing manner of the connection structure may be set according to needs, for example, may include at least one of an electromagnetic adsorption structure and a negative pressure adsorption structure, so that the chip 30 may be fixed on the platform by electromagnetic adsorption or negative pressure adsorption.

The embodiment also provides a sequencer, which comprises the chip blending device, wherein the chip blending device can be matched with a camera and other acquisition devices to acquire images at all positions on the chip 30. The chip mixing device is provided with an initial state and a mixing state, wherein when the chip mixing device is in the initial state, a chip carried by the chip mixing device is matched with the acquisition device, the chip carried by the chip mixing device and the acquisition device are kept at a preset relative position, the chip mixing device can acquire image information by the acquisition device at the moment, and the acquisition device can acquire information of the chip 30 at the moment, so that subsequent analysis and other processes are realized. When the chip mixing device is in a mixing state, the chip mixing device moves at the moment, and the platform and the chip 30 on the platform swing, so that the reagent in the chip 30 is uniformly mixed. The acquisition device can be a lens, and in an initial state, the lens is vertical relative to the chip and horizontally moves so as to complete image signal acquisition of the whole chip. It should be noted that the initial state and the equilibrium position of the platform may be the same or different.

In order to realize accurate detection of the state of the chip mixing device, the sequencer of the embodiment further comprises a detection device electrically connected with the acquisition device, wherein the detection device is matched with the chip mixing device and can detect the position state of the chip. The detection device may employ a position sensor or other component, for example, an infrared distance sensor, as required, so long as the chip blending device, more specifically, the detection of the platform state can be realized. The detecting device is used for determining that the chip is located at a preset relative position in an initial state, and when the detecting device detects that the chip blending device is located at the initial state, the chip blending device can be matched with the collecting device to realize image collection, so that the detecting device feeds back the state of the chip blending device, and the collecting device is controlled to act through a controller and other components, so that information of the chip 30 is collected.

It should be noted that, in the above embodiments, a plurality refers to at least two.

From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

1. the problems of risk of damaging a detection chip and a sample in a mode of using pressure to suck, push and load a uniformly mixed sample and/or a reagent in the prior art are solved;

2. the loading function of the sample and the reagent is realized, the mixing of the reagent and the sample in the chip reaction area is realized, the operations such as pressurization and the like are not needed, the situation that the chip is damaged due to improper pressure control is avoided, and the sample adding and mixing process is simple, stable and reliable;

3. the repeated use of the reagent is realized, the reagent consumption is reduced, and the cost is saved;

4. the recovery of waste liquid and the cleaning of chips can be realized;

5. the sequencer is reasonable in layout, efficient and reliable.

It will be apparent that the embodiments described above are merely some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.

It should be noted that the terms "first," "second," and the like in the description and claims of the present application and the above figures are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used may be interchanged where appropriate such that embodiments of the present application described herein may be implemented in sequences other than those illustrated or described herein.

The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A chip blending device, comprising:

a base (100);

the shaking mechanism (110) is movably arranged on the base (100), and the chip (30) is borne on the shaking mechanism (110);

the liquid inlet module (10), the liquid inlet module (10) is used for placing the liquid inlet end of the chip (30), and the liquid inlet module (10) is provided with a liquid inlet channel (11) in butt joint fit with the liquid inlet (31) of the chip (30);

go out liquid module (20), go out liquid module (20) are used for placing go out liquid end of chip (30), go out liquid module (20) have with liquid outlet (32) butt joint complex play liquid channel (21) of chip (30), shake even mechanism (110) drive chip (30) go on one end of chip (30) rise, the other end of chip (30) descends to and at least one among the plane in chip (30) place swing is in order to mix reagent in chip (30).

2. The chip blending device according to claim 1, wherein the shaking mechanism (110) comprises:

the chip (30), the liquid inlet module (10) and the liquid outlet module (20) are placed on the platform;

the driving piece is in driving connection with the platform and drives the platform to swing; and/or the platform is rotatably connected with the base (100) through an adapter (120), and the driving piece is in driving connection with the adapter (120) and drives the platform to swing through driving the adapter (120).

3. The chip mixing device according to claim 2, wherein,

the driving piece comprises a lifting mechanism, and the lifting mechanism is connected with the platform and drives the platform to swing; and/or the number of the groups of groups,

the platform is rotatably connected with the base (100) through the adapter (120), the adapter (120) comprises at least one of a ball head and a rotating shaft, and when the adapter (120) comprises the rotating shaft, the axis of the rotating shaft is arranged non-perpendicularly to the surface of the chip (30).

4. The chip blending device according to claim 2, wherein the platform is rotatably connected with the base (100) through an adapter (120), the adapter (120) comprises a rotating shaft, an axis of the rotating shaft is parallel to a surface of the chip (30) and perpendicular to a length direction of the chip (30), and an axis of the rotating shaft is located directly below a center line of the length direction of the chip (30).

5. The chip blending device according to claim 2, wherein the shaking mechanism (110) further comprises a reset member, and the reset member is connected to the platform and drives the platform to swing to a predetermined balance position.

6. Chip blending device according to claim 1, wherein the maximum angle formed between the shaking mechanism (110) and the horizontal plane when it is swung is 45 °.

7. The chip blending device according to any one of claims 1 to 6, further comprising:

a waste liquid module (40);

the electromagnetic valve module (50), electromagnetic valve module (50) with liquid outlet (32), go out liquid module (20) with waste liquid module (40) three are connected, and control go out liquid outlet (32), go out liquid module (20) with the communication relation between waste liquid module (40) three.

8. The chip mixing device according to claim 7, wherein the waste liquid module (40) comprises a waste liquid busbar (41), a pump body (42) and a waste liquid barrel (43) which are sequentially communicated, the waste liquid busbar (41) is communicated with the electromagnetic valve module (50), and the pump body (42) provides power for extracting liquid in the liquid outlet module (20).

9. Chip blending device according to claim 1, wherein the shaking mechanism (110) comprises a platform having a plurality of mounting locations (70) for receiving the chips (30), each mounting location (70) being arranged in an array and/or in an annular arrangement.

10. The chip blending device of claim 1, further comprising:

a kit (60), the kit (60) having a plurality of receiving cavities for storing reagents;

and communication pipelines for communicating the accommodating chambers with the chips (30), wherein a first end (80) of each communication pipeline is matched with the accommodating chamber, and the first end (80) and/or the reagent kit (60) are arranged in an adjustable position so that the communication pipelines are matched with different accommodating chambers in a communicating way.

11. The chip mixing device according to claim 10, wherein the reagent cartridge (60) is a rotary disc type reagent cartridge (60), and each of the accommodating chambers is rotatably provided along a circumferential direction of the reagent cartridge (60) to change an accommodating chamber cooperating with the first end (80) of the communication line.

12. The chip mixing device according to claim 10, wherein each of the receiving chambers is arranged in a line, and the reagent cartridge (60) is movably arranged along the line to change the receiving chamber to be engaged with the first end (80) of the communication line.

13. Chip blending device according to claim 11, wherein the shaking mechanism (110) comprises a platform having a plurality of mounting locations (70) for receiving the chips (30), each of the mounting locations (70) being rotatably arranged in a circumferential direction of the kit (60), the communication line extending in a radial direction of the kit (60) to change a mating relationship between each of the receiving cavities and each of the mounting locations (70).

14. The chip blending device according to any of claims 1 to 6, wherein the shaking-up mechanism (110) has a connection structure for fixing the chip (30) on the shaking-up mechanism (110), the connection structure comprising at least one of an electromagnetic adsorption structure, a negative pressure adsorption structure.

15. A sequencer, characterized by comprising the chip mixing device according to any one of claims 1 to 14, wherein the chip mixing device has an initial state and a mixing state, when the chip mixing device is in the initial state, a chip carried by the chip mixing device and the signal acquisition device are kept at a preset relative position, and when the chip mixing device is in the mixing state, the chip mixing device moves and mixes the reagents in the chip (30).

16. The sequencer according to claim 15, further comprising detection means electrically connected to said acquisition means for detecting the position of said chip, said detection means being adapted to determine in said initial state that said chip is located in said predetermined relative position.