CN117625362B - Blood-derived neurogenic exosome enrichment device - Google Patents

Abstract

A blood-derived neurogenic exosome enrichment device comprises a bottom plate, a device and a consumable, wherein the bottom plate is used for bearing an instrument and a consumable for automatically enriching exosomes; the box cover is arranged on the bottom plate, forms a closed space with the bottom plate, and is provided with instruments and consumables for automatically enriching exosomes; the arrangement of the closed space ensures that the device keeps running in a non-cover state; the closed space is internally and sequentially provided with a sample tube placing rack, a consumable placing rack, a reagent placing rack, an oscillation incubator placing rack and a centrifugal instrument in parallel along the X-axis direction, and the closed space further comprises a moving structure for controlling the movement of the X-axis and the Y-axis in the Z-axis three-dimensional direction; in order to ensure the effective use of the device space, a longitudinal vertical plate, two transverse vertical plates and a horizontal plate which is vertical to the transverse vertical plates are arranged on the bottom plate, and the volume of the sample tube is arranged within 2 ml. The small-capacity sample tube and the plate body divide the closed space into a plurality of structural setting spaces, so that the airflow space under the uncapping operation of the device is reduced, and the miniaturization of the device is promoted.

Description

Blood-derived neurogenic exosome enrichment device

Technical Field

The invention belongs to the technical field of medical diagnosis instruments, and particularly relates to a blood-source neurogenic exosome enrichment direction for diagnosing neurodegenerative diseases, in particular to a blood-source neurogenic exosome enrichment device.

Background

Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheath, which worsen over time to become dysfunctional. Such as Alzheimer's Disease (AD), parkinson's Disease (PD), avirus disease, etc. At present, the clinical diagnosis of neurodegenerative diseases depends on positron emission computed tomography, and diseases often progress to an untreated and recovered stage when pathological changes occur. The other mode is to detect the related biomarker through cerebrospinal fluid, and the mode can be diagnosed in advance, but the sampling mode of the cerebrospinal fluid is traumatic to the human body, and the willingness of the patient is not high.

Along with the deep research of exosomes, the neurogenic exosomes in blood can be used as indexes for diagnosing neurodegenerative diseases, the diagnosis of the diseases can be greatly advanced by the mode, blood acquisition is simple, but the neurogenic exosomes in blood can be acquired through enrichment, the enrichment is long in time at present, and large-scale cannot be formed.

An automated device for effectively enriching neurogenic exosomes in blood and an automated device for effectively enriching exosomes 202221918838.5 in the prior art 202110247374.3; an automatic product for enriching neurogenic exosomes is disclosed, but one discloses a conceptual technical scheme of a whole process, and the other discloses a larger technical scheme divided into double-layer spaces for accommodating various instruments. Both of the above-mentioned technical solutions are difficult to implement in clinic, so that an effective clinical technical solution is required; in particular to a blood-derived neurogenic exosome enrichment device.

Disclosure of Invention

An automatic device for effectively enriching neurogenic exosomes in blood in the prior art 202110247374.3 is a conceptual enrichment mode, the implementation concept is that the exosomes are enriched by partitioning the centrifugation and oscillation incubation and arranging a plurality of partitions, and the arrangement needs more structures and occupies larger space; while 202221918838.5 an automated device for effectively enriching exosomes is a partition in a concept of conceptualization, ensuring that small batches of samples are realized, wherein samples for single operation are all completed in one batch, the number of samples completed each time is very effective, and if the number of samples is increased, the equal proportion of each structure is required to be increased, the space required to be occupied in the way is huge, that is, the way of using completely-spaced upper and lower double-layer spaces is realized, one layer is used for enriching the samples, and one layer is used for accommodating other related structures, such as a bottom part of a centrifugal machine and an oscillation incubator is embedded into a lower-layer space in an embedding way. In practical use, both types are difficult to popularize and use due to the fact that the volume is too large and the sample size of a single operation is limited. Therefore, the invention realizes the miniaturization of the device through reasonable layout.

A blood-derived neurogenic exosome enrichment device comprises

The bottom plate is used for bearing instruments and consumables for automatically enriching exosomes;

The box cover is arranged on the bottom plate and forms a closed space with the bottom plate, and the instruments and consumables for automatically enriching exosomes are arranged in the closed space; the arrangement of the closed space enables all reagents and sample tubes to be operated in a non-cover state;

The closed space is internally provided with:

The centrifugal instrument is used for centrifuging the sample tube in the exosome enrichment process and is arranged at a first edge position on one side of the bottom plate;

The sample tube placing rack is used for placing the sample tubes;

The consumable rack is used for placing the reaction tube and the pipette in the process and is divided into a reaction tube area and a pipette area 322;

The reagent placing rack is a low-temperature placing rack and is used for placing a plurality of reagents for automatically enriching exosomes;

the vibration incubator comprises a vibration incubator, a vibration incubator and a vibration incubator, wherein the vibration incubator is used for completing vibration incubation in the exosome enrichment process;

the moving structure is a combining structure and comprises a pipe body moving structure and a liquid moving structure which are combined; the pipe body moving structure and the liquid moving structure are provided with a Z-axis lifting structure; the device also comprises an X-axis moving structure and a Y-axis moving structure which control the merging structure and the sample tube placing frame, the consumable placing frame, the reagent placing frame and the oscillation incubator placing frame which are arranged below to move relatively in the X-axis and Y-axis directions;

a control structure for controlling the operation of the device;

The sample tube placing rack, the consumable placing rack, the reagent placing rack and the oscillating incubator placing rack have the same length in the Y-axis direction, and the heights in the Z-axis direction are uniform as a whole; the sample tube placing rack, the consumable placing rack, the reagent placing rack, the oscillation incubator placing rack and the centrifugal instrument are arranged in parallel along a straight line along the X-axis direction, and no distance or a distance between each rack body of the sample tube placing rack, the consumable placing rack, the reagent placing rack and each rack body of the oscillation incubator placing rack is smaller than 1cm;

Further, the box cover is a five-sided wrapped box cover except the bottom, the front side surface of the box cover is provided with a plurality of box doors, and the box doors can be respectively opened to correspond to different inner structure areas; this approach can ensure that the relative replacement actions are performed on each internal structure without affecting other actions.

Further, the bottom plate is a rectangular plate, and the centrifugation apparatus, all parts of sample tube rack, consumable rack, reagent rack and vibration incubator rack are all disposed above the bottom.

Further, the volume of the single sample tube is 2ml or less; the volume of a single sample tube is reduced, so that the corresponding devices for enriching the exosomes are reduced, and the purpose of reducing the volume of the device is achieved to the greatest extent by parallel arrangement, so that the miniaturization of the device is realized.

Further, the sample tube placing rack is used for placing at least two groups of sample tubes, and the number of each group of sample tubes is consistent with that of the centrifugal tube holes in the centrifugal instrument; the number of reaction tubes or pipettes on the consumable rack is the number required for all groups of sample tubes; the reagent amount of the reagent placing rack is more than or equal to the reagent amount for completing enrichment of all groups of sample tubes on the sample tube placing rack; the vibration incubator rack is provided with vibration incubation holes the same as the sample tube rack in number;

Further, the tube body setting holes on the sample tube rack and the tube body setting holes corresponding to the reaction tubes on the consumable rack are identical in array mode of the tube body setting holes on the oscillation incubation rack, and the initial and the end positions along the Y axis are identical, so that the moving distances of the X axis and the Y axis of the sample tube and the reaction tubes are identical, and the programming complexity is reduced.

Further, the aperture of the reagent hole of the reagent containing structure on the reagent placing rack is different from the aperture of the hole arranged on the tube body, but the circle center position array mode of each hole is the same, and the number of the reagent hole rows is equal to the number of the sample tube groups.

Further, a longitudinal vertical plate is arranged on the bottom plate, and the whole longitudinal vertical plate is arranged along the X-axis direction; the longitudinal vertical plate divides the bottom plate into a front area and a rear area, and centrifugal instruments arranged in parallel are arranged below the front area, and the sample tube placing rack, the consumable placing rack, the reagent placing rack and the oscillation incubator placing rack are arranged below the front area; above the front region is a moving structure that achieves at least 2 axial movements; the longitudinal vertical plate is a plate with a bending angle; is used for meeting the partition arrangement of the centrifugal instrument with different lengths of other placing racks.

Further, a transverse vertical plate which is vertical to the longitudinal vertical plate and the bottom is arranged on the longitudinal vertical plate; the two transverse vertical plates are arranged, the first transverse vertical plate is arranged at a second edge position, and the second edge position and the first edge position are two edge positions opposite along the long edge of the bottom plate; the second transverse vertical plate is arranged at the bending position of the longitudinal vertical plate; the purpose of stably arranging the vertical plate on the bottom plate is achieved.

Further, a horizontal plate perpendicular to both the horizontal vertical plate and the longitudinal vertical plate is arranged on the horizontal vertical plate and the longitudinal vertical plate, and the longitudinal vertical plate extends to the upper part of the horizontal plate to divide the horizontal plate into a front area and a rear area.

Wherein the first region is a front lower region, the second region is a front upper region, the third region is a rear lower region, and the fourth region is a rear upper region;

further, a first rotating shaft for controlling the combination structure to move in the X-axis direction of the combination structure is arranged in the second area, the first rotating shaft is a screw rotating shaft, the combination structure is provided with a first combination structure which is matched with the first rotating shaft, and the first combination structure is driven to reciprocate along the first rotating shaft by different rotating directions of the first rotating shaft; the first rotating shaft is connected with a belt pulley I through a first vertical transverse plate; the fourth area is provided with an X-axis direction driving motor, and a motor rotating shaft is connected with a belt pulley II through a first transverse vertical plate; the belt pulley I is connected with the belt pulley II through a belt I, so that the belt pulley I is driven by the X-axis driving motor to rotate, the belt pulley I is driven by the belt I to move, the belt I is driven by the belt II to rotate, and the belt pulley II is driven by the belt II to rotate; the rotation of the first rotating shaft drives the reciprocating motion of the merging structure; through this kind of reduction overall length demand, the motion structure of X axle direction is introduced into two spaces through the belt pulley, has increased space utilization's effectiveness.

Further, the second area is an area meeting the arrangement of the rotating shaft, is smaller than the first area, the horizontal plate does not cover the working areas of the sample tube placing rack, the consumable placing rack, the reagent placing rack and the oscillating incubator placing rack, and the merging structure is arranged in the area in front of the horizontal plate; the sample tube placing rack, the consumable placing rack, the reagent placing rack and the working area of the oscillating incubator placing rack extend into the centrifugal instrument from the front of the horizontal plate.

Further, the lowest end of the tube body moving structure is a tube body clamping head for clamping the tube body, and the liquid moving structure comprises a liquid transferring head for completing pipette acquisition, liquid suction and pushing out below; the waste collection structure is arranged at a second edge position of the bottom plate, the second edge position is opposite to the first edge position of the centrifugal device, and the waste collection structure and the first transverse vertical plate are arranged at different positions on the same transverse edge of the bottom; the waste collecting structure comprises a collecting opening, and when the combining structure moves to the second edge position of the first rotating shaft, the structure on the inner side of the tube body clamping head and the pipetting head moves to the upper part of the collecting opening.

Further, an extending hole I is formed in the centrifugal instrument, and the extending hole I is a hole for enabling the pipe body clamping head and the liquid transferring head to extend into the pipe and liquid taking; when the merging structure moves to the first edge position of the first rotating shaft; the pipe body clamping head and the inner side structure of the pipetting head move to the upper part of the extending hole.

Further, a waste liquid suction structure is arranged above the centrifugal structure, the waste liquid suction structure is fixedly arranged on the vertical plate, the waste liquid suction structure only moves in the Z-axis direction, and a Z-axis moving structure is arranged; the waste liquid sucking structure comprises waste liquid sucking and releasing functions, and an extending hole II is arranged below the waste liquid sucking structure and is a hole for meeting the extending of the waste liquid sucking structure; a waste liquid collecting cavity is arranged in the centrifugal instrument, and a waste liquid collecting hole is arranged above the waste liquid collecting cavity; when the waste liquid suction structure sucks waste liquid from the sample tube, the waste liquid suction structure rotates through the centrifugal instrument to collect the waste liquid Kong Zhengchong and stretch into the second hole, so that the release of the waste liquid is completed.

Further, along the long limit direction of bottom plate from the second edge position to first edge position direction setting gradually, sample tube rack, consumptive material rack, reagent rack, vibration incubator rack and centrifugation apparatus.

The beneficial effects of the invention are as follows:

the arrangement mode that the centrifugal apparatus is parallel to each rack and the height is basically consistent can ensure the movement consistency of the moving structure when the device integrally operates, thereby reducing unnecessary space waste; in addition, the height is consistent, as a result of lifting each frame body, the Z-axis moving distance of the moving structure can be reduced in the mode, and the purpose of meeting enrichment requirements through a smaller moving structure is achieved.

The closed space formed by the box cover and the bottom plate is arranged in the closed space in parallel with each part of each structure, and the volume of the sample tube is reduced; the whole device can maintain the uncovered operation state, and the smaller airflow space of the uncovered operation area is ensured, and the validity of the uncovered operation is ensured.

The arrangement of the transverse vertical plates, the longitudinal vertical plates and the horizontal plates can divide the closed space into effective spaces and further reduce the space size of the exosome enrichment area; in addition, the effective setting space of other instruments is also satisfied, and especially the control structure and other structures are arranged in a partitioning way, so that the interference of the operation process on the circuit of the control structure can be effectively avoided.

Drawings

FIG. 1 is a schematic structural view of an embodiment of the present invention without a cover and with a moving structure moved into position with a centrifugal instrument;

FIG. 2 is a schematic structural view of an embodiment of the present invention without a cover and with the moving structure moved to a waste collection structure position;

FIG. 3 is a schematic view of the device in the fully closed state of the case cover according to the present invention;

FIG. 4 is a schematic view of the device in the open state of a fan case cover according to the present invention;

FIG. 5 is a schematic view of the rear side view of the device without cover according to the present invention

FIG. 6 is a schematic view showing the front side view of the plate body combining parts of the bottom plate, the longitudinal vertical plate, the transverse vertical plate and the like;

FIG. 7 is a schematic view of the rear side view of the plate body joining portion of the base plate, the longitudinal vertical plate, the transverse vertical plate, etc. according to the present invention;

FIG. 8 is a schematic view of a partially enlarged structure of a first pulley and a second pulley according to the present invention;

FIG. 9 is a schematic view of the structure of the bottom surface of the placement frame with the rotation axis of the Y-axis direction driving motor perpendicular to the Y-axis;

FIG. 10 is a schematic view of a side view, longitudinal cross-sectional structure of a rack with a rotation axis of a Y-axis direction drive motor perpendicular to the Y-axis;

FIG. 11 is a schematic diagram showing a side view structure of a rack with a rotation shaft of a Y-axis direction driving motor parallel to a Y-axis;

FIG. 12 is a flow chart of blood-derived neurogenic exosomes enrichment in accordance with the present invention;

Description of the main reference numerals

11. A bottom plate; 12. a longitudinal vertical plate; 121. a wire passing through hole; 13. a first transverse vertical plate; 14. a second transverse vertical plate; 15. a horizontal plate; 2. a case cover; 31. a sample tube rack; 32. a consumable rack; 321. a reaction tube region; 322. a pipette zone; 33. a reagent rack; 34. oscillating the incubator rack; 35. centrifuging the instrument; 351. the first hole is extended; 352. the second hole is extended; 36. merging structures; 361. a tube body clamping head; 362. a pipetting head; 37. a control structure; 41. a first rotating shaft; 42. a first combination structure; 43. a first belt pulley; 44. a belt pulley II; 45. a first belt; 46. an X-axis direction driving motor; 5. a waste collection structure; 51. a collection port; 6. a waste liquid sucking structure;

711. Lifting the column; 712. a transverse link; 72. a containing frame; 721. a second combination structure; 73. a bearing plate; 731. a surrounding structure; 74. a Y-axis direction driving motor; 75. a transition plate; 751. a transition hole; 761. a support plate; 762. a second rotating shaft; 763. a belt pulley III; 764. a belt pulley IV; 765. and a second belt.

Detailed Description

Example 1

Note that: the first edge position is the edge position of the bottom plate 11 in the direction corresponding to the direction in which the centrifugal device 35 is arranged; the second edge position is the other edge position of the long side of the bottom plate 11. The first edge position of all the structures is the position corresponding to the direction in which the centrifugal instrument 35 is arranged, this edge position being merely the edge position relative to the structure itself and not the position of the centrifugal instrument 35. The horizontal transverse direction is the X-axis direction, the longitudinal direction is the Y-axis direction, and the vertical direction is the Z-axis direction; in the present invention, the long side direction of the base plate 11 is the X-axis direction, the short side direction is the Y-axis direction, the up-down direction is the Z-axis direction, and the X-axis, the Y-axis and the Z-axis are described as being disposed in the upper direction.

Referring to fig. 1-5; a blood-derived neurogenic exosome enrichment device comprises a bottom plate 11, a device and consumable materials, wherein the bottom plate is used for carrying automatic exosome enrichment devices; the box cover 2 is arranged on the bottom plate 11 and forms a closed space with the bottom plate 11, and instruments and consumables for automatically enriching exosomes are arranged in the closed space; the arrangement of the closed space enables all reagents and sample tubes to be operated in a non-cover state; the closed space is internally provided with: a centrifugal device 35, which is used for centrifuging the sample tube in the exosome enrichment process and is arranged at a first edge position on one side of the bottom plate 11; a sample tube holder 31 for holding a sample tube; the consumable rack 32 is used for placing the reaction tube and the pipette in the process and is divided into a reaction tube area 321 and a pipette area 322; a reagent rack 33, which is a low-temperature rack for placing a plurality of reagents for automatically enriching exosomes; a shake incubator rack 34, including a shake incubator thereon, for performing shake incubations during exosome enrichment;

A moving structure for controlling the X-axis moving structure and the Y-axis moving structure of the sample tube placing frame 31, the consumable placing frame 32, the reagent placing frame 33, and the oscillation incubator placing frame 34 to move relatively in the X-axis and Y-axis directions; and also includes a Z-axis movement. The moving structure is a combining structure 36, which includes a pipe moving structure and a liquid moving structure that are combined; the pipe body moving structure and the liquid moving structure are provided with a Z-axis lifting structure; the device also comprises an X-axis moving structure and a Y-axis moving structure which control the combining structure 36 and the sample tube placing frame 31, the consumable placing frame 32, the reagent placing frame 33 and the oscillation incubator placing frame 34 which are arranged below and move relatively in the X-axis and Y-axis directions;

A control structure 37 for controlling the movement of the moving structure and controlling the rotation of the centrifugal structure centrifuge;

The sample tube placing rack 31, the consumable placing rack 32, the reagent placing rack 33 and the oscillation incubator placing rack 34 have the same length in the Y-axis direction and have the same height in the Z-axis direction; the sample tube placing rack 31, the consumable placing rack 32, the reagent placing rack 33 and the oscillation incubator placing rack 34 have no distance or the distance between the adjacent rack bodies is less than 1cm; the sample tube rack 31, the consumable rack 32, the reagent rack 33, the oscillation incubator rack 34, and the centrifugal device 35 are arranged in parallel along a straight line along the X-axis direction;

The box cover 2 is a five-sided wrapped box cover 2 except the bottom, the front side surface of the box cover is provided with a plurality of box doors, and the box doors can be respectively opened to correspond to different inner structure areas; this approach can ensure that the relative replacement actions are performed on each internal structure without affecting other actions.

In a more preferred embodiment, the size of the overall device is controlled by the size of the centrifuge instrument 35, and the number of sample tubes per set is set to 8 and the number of sets is set to 3 in order to control the device to the proper size and meet the current clinical small batch sample size enrichment and detection requirements. The device can meet the requirements of the device on the size and the current clinic to the greatest extent. Of course, the number of sample tubes per set of the device can be increased or decreased as required.

In a more preferred embodiment, the size of the space in which the uncapped sample tube and reagent bottle are located is further reduced; a longitudinal vertical plate 12 is arranged on the bottom plate 11, and the longitudinal vertical plate 12 is integrally arranged along the X-axis direction; the longitudinal vertical plate 12 divides the bottom plate 11 into a front area and a rear area, and a centrifugal instrument 35, a sample tube placing rack 31, a consumable placing rack 32, a reagent placing rack 33 and an oscillation incubator placing rack 34 are arranged below the front area in parallel; above the front region is a displacement structure that effects at least 2 axial displacements.

More preferred embodiments, refer to FIGS. 6-7; because the centrifuge instrument 35 is different in length from the other racks, the other racks include a sample tube rack 31, a consumable rack 32, a reagent rack 33, and an oscillation incubator rack 34; the vertical plates 12 are plates with bending angles in such a way that the spacing in the front-rear direction along the entire bottom long-side direction is achieved. A transverse vertical plate perpendicular to both the longitudinal vertical plate 12 and the bottom is provided on the longitudinal vertical plate 12; the two transverse vertical plates are arranged, the first transverse vertical plate 13 is arranged at a second edge position, and the second edge position and the first edge position are two edge positions opposite along the long side of the bottom plate 11; the second transverse vertical plate 14 is arranged at the bending position of the longitudinal vertical plate 12; the purpose of stably arranging the vertical plate on the bottom plate 11 is achieved. A horizontal plate 15 is provided on the horizontal vertical plate and the longitudinal vertical plate 12, and the longitudinal vertical plate extends above the horizontal plate 15 to divide the horizontal plate 15 into front and rear two areas. This arrangement results in 4 areas of transverse, longitudinal and horizontal plates 15. By the mode, the three-dimensional space can be effectively used, the utilization of the time space is maximized, and the whole volume of the device is finally reduced.

The first region is a front lower region, and a centrifuge 35, a sample tube rack 31, a consumable rack 32, a reagent rack 33, and an oscillation incubator rack 34 are provided.

Referring to fig. 8; the second area is a front upper area, a first rotating shaft 41 for realizing the movement of the merging structure 36 along the X-axis direction is arranged, the first rotating shaft 41 is a screw rotating shaft, the merging structure 36 is provided with a first combining structure 42 matched with the first rotating shaft 41, and the first combining structure 42 is driven to reciprocate along the first rotating shaft 41 by different rotating directions of the first rotating shaft 41; the first shaft 41 is connected to a pulley one 43 by a first vertical cross plate. The second area is an area meeting the setting of the rotating shaft and is smaller than the first area. The horizontal plate 15 does not cover the working areas of the sample tube holder 31, the consumable holder 32, the reagent holder 33, and the shaking incubator holder 34, and the merging structure 36 is provided in the front area of the horizontal plate 15; from the front of the horizontal plate 15, into the working area of the centrifuge 35, the sample tube holder 31, the consumable holder 32, the reagent holder 33 and the shaking incubator holder 34.

The third area is a rear lower area, and a control structure 37 is provided, and the control structure 37 includes a circuit board, various sensors, and the like. The first end of the second transverse vertical plate 14 is connected to a corresponding portion of the centrifugal apparatus 35 of the first vertical plate and is flush with the transverse edge of the first vertical plate; the second end of the second transverse vertical plate 14 is flush with the edge of the horizontal plate 15 in such a way as to divide the third zone into two zones of different sizes, with the control structure 37 being arranged at the corresponding larger zone and the other structures being arranged at the smaller zone. By means of the arrangement, the third area is fully utilized, and the third area and the box wall of the box cover 2 form a relative undisturbed space, so that the drying of the corresponding area of the control structure 37 in the use process is ensured.

The fourth area is a rear upper area, an X-axis direction driving motor 46 is arranged, and a motor rotating shaft is connected with a belt pulley II 44 through a first transverse vertical plate 13;

The first belt pulley 43 and the second belt pulley 44 are connected through the first belt pulley 45, so that the first belt pulley 43 is driven to rotate by the X-axis driving motor, the first belt pulley 43 drives the first belt pulley 45 to move, the first belt pulley 45 drives the second belt pulley 44 to rotate, and the second belt pulley 44 drives the first rotating shaft 41 to rotate; rotation of the first shaft 41 moves the merging structure 36 back and forth. Through the above arrangement, the position of the X-axis driving motor is changed through the belt pulley, so that the X-axis driving motor is arranged in the direction parallel to the first rotating shaft 41, the purpose of reducing the length direction requirement can be achieved, and the purpose of reducing the volume of the device is further achieved through space utilization.

More preferred embodiments, refer to FIGS. 1-2; the lower end of the tube moving structure is a tube clamping head 361 for clamping the tube, and the liquid moving structure comprises a pipetting head 362 for completing pipette acquisition, liquid suction and pushing out. The waste collection structure 5 is arranged at a second edge position of the bottom plate 11, the second edge position is opposite to the first edge position of the centrifugal device 35, and the waste collection structure 5 and the first transverse vertical plate 13 are arranged at different positions on the same transverse edge of the bottom; the waste collection structure 5 includes a collection port 51, and when the combining structure 36 moves to the second edge position of the first rotating shaft 41, the inner structure of the tube holding head 361 and the pipetting head 362 moves to above the collection port 51. More preferably, the maximum distance between the tube holding head 361 and the pipetting head 362 is equal to or less than the width of the collection port 51 of the waste collection device; when the combining structure 36 is moved to the second edge position of the first rotation shaft 41, both the tube holding head 361 and the pipetting head 362 are simultaneously disposed above the collection port 51, and such arrangement can reduce the problem of erroneous discard of waste by increasing the width of the collection port 51, and the long side length of the entire bottom plate 11 is not increased by the increase of the width of the collection port 51 because the long side length setting of the bottom plate 11 depends on the setting of the length of the first rotation shaft 41.

In a more preferred embodiment, the edge of the collection mouth 51 of the waste collection structure 5 is the edge of the waste collection structure 5; the volume of the waste collection structure 5 can be increased by extending in the bottom short side direction, and the volume of the waste collection structure 5 can be further increased without affecting the length of the bottom long side, and the waste collection structure 5 can be extended in the direction of the first edge position along the bottom long side, specifically, the sample tube rack 31 and the consumable rack 32 can be extended in the bottom space.

In a more preferred embodiment, the vertical plate corresponding to the first area is provided with a through-line hole 121 for satisfying the pipeline and the line communication in the front and rear areas.

More preferred embodiments, refer to fig. 1; the centrifugal device 35 is provided with an extending hole I351, and the extending hole I351 is a hole for meeting the requirement that the pipe body clamping head 361 and the liquid transferring head 362 extend into the pipe taking and liquid taking; when the merging structure 36 moves to the first edge position of the first rotation shaft 41; the inner structures of the tube holding head 361 and the pipetting head 362 move to above the access hole. In this way, the work of the tube holding head 361 and the pipetting head 362 is ensured.

In a more preferred embodiment, the rotating structure inside the centrifugal apparatus 35 can meet the requirement of rapid rotation during centrifugation, and can also memorize the initial centrifugal position of the centrifugal structure, ensure that the initial centrifugal position is the same as the final centrifugal position, rotate in the same direction, and perform the tube taking and placing operation and the liquid extraction operation during the process.

In a more preferred embodiment, the working time required by the centrifugation process in the exosome enrichment process is shorter, but the working time required by the oscillation incubation process is longer, if the tube body can be moved to the oscillation incubation structure as soon as possible for oscillation incubation, the whole exosome enrichment efficiency can be greatly improved, and then how to operate can be achieved to enable the tube body to be moved to the oscillation incubation structure module as soon as possible, the rationalization of the centrifugation process is a key factor for solving the problem, in the prior art, the tube body moving structure and the liquid moving structure are independently arranged, the two structures are respectively operated in a separated arrangement mode, when the two structures are required to be mutually avoided under the condition of unsuitable conditions, and the merging structure 36 in the invention solves the problem of avoidance; however, the long distance from the centrifugal structure to the waste collection structure 5, the long time, and how to reduce the operations from the centrifugal structure to the waste collection structure 5 are a solution to the problem. Referring to fig. 1; the specific implementation mode is as follows: a waste liquid suction structure 6 is arranged above the centrifugal structure, the waste liquid suction structure 6 is fixedly arranged on a vertical plate, the waste liquid suction structure 6 only moves in the Z-axis direction, and a Z-axis moving structure is arranged; the waste liquid sucking structure 6 comprises waste liquid sucking and releasing functions, and an extending hole II 352 is arranged below the waste liquid sucking structure 6, and the extending hole II 352 is a hole for meeting the extending of the waste liquid sucking structure 6; a waste liquid collecting cavity is arranged in the centrifugal instrument 35, and a waste liquid collecting hole is arranged above the waste liquid collecting cavity; after the waste liquid is sucked from the sample tube to the waste liquid sucking structure 6, the waste liquid collecting Kong Zhengchong is inserted into the second hole 352 through the rotation of the centrifugal device 35, so that the release of the waste liquid is completed.

In a more preferred embodiment, in order to better realize the arrangement of each parallel rack and the centrifugal apparatus 35, the following arrangement is performed, specifically: the sample tube placing rack 31, the consumable placing rack 32, the reagent placing rack 33, the oscillation incubator placing rack 34 and the centrifugal instrument 35 are sequentially arranged from the second edge position to the first edge position along the long edge direction of the bottom plate 11; this kind of arrangement guarantees that replace most frequent centrifugation apparatus 35 and vibration incubation apparatus next-door neighbour setting, saves time, and sample tube rack 31 and consumptive material rack 32 are the no power structure, on setting it to the second edge position orientation, can be at the idle sufficient space of bottom, carries out the setting of waste placement structure, realizes space utilization maximize.

More preferred embodiments, the height of the highest points of the centrifuge instrument 35, sample tube holder 31, consumable holder 32, reagent holder 33 and shaking incubator holder 34 is uniform or the difference in height is less than 3cm; in this way, the risk of collision between the individual structures during the back and forth movement due to excessively high height differences can be avoided. The preferable scheme is equal-height setting.

When the above technical scheme is used for miniaturization of the uncapping operation scheme in the closed space, the core limiting factor of the miniaturization is found, namely, the volume of the sample tube, the size of the corresponding centrifugal instrument 35, the setting mode of each placement frame and the like are core limiting factors, and the limiting factors and the design of the corresponding technical scheme are not available in the prior art.

Example 2

On the basis of embodiment 1, the Y-axis moving structure is arranged at the position of the rack, and the specific implementation mode is as follows: the sample tube rack 31, consumable rack 32, reagent rack 33, and shake incubator rack 34 all include racks that provide a Y-axis movement structure for Y-axis movement; the setting of setting up Y axle moving structure on the rack and moving the structure with the X axle direction that first pivot 41 provided is for realizing respectively that rack and merger structure follow the relative two-way removal of X axle and Y axle direction through two parts, set up the accurate degree that moving structure can effectually improve the motion through two parts, can reduce the complexity that a 42 parts of combination structure set up in addition, two other parts set up the moving structure of a direction respectively, the space requirement of each structure of further optimizing, make the utilization maximize of space, and then further contribute to realizing miniaturization. With this arrangement, the merge structure 36 only moves in the X-axis and Z-axis directions.

In a more preferred embodiment, in order to achieve consistency of heights of the structures and ensure that a Y-axis moving structure is arranged on the placement frame, a specific frame body setting technical scheme is described by taking a structure of commonality of the placement frame as an example:

referring to fig. 9-11; each rack includes the structure:

the lifting frame is used for lifting the corresponding placing frame to ensure the height of the corresponding placing frame to be consistent or basically consistent with the height of other placing frames and the height of the centrifugal instrument 35, and comprises lifting parts at two ends, and a hollow space is formed in the middle of the lifting parts at two ends;

A housing frame 72 having a corresponding tube body setting hole or reagent bottle housing hole;

a support bracket of the accommodating frame 72 is arranged above the lifting frame, and the accommodating frame 72 is provided with a movable accommodating frame 72; and the Y-axis direction of the support bracket of the accommodating frame 72 provides a guide rail for the movement of the accommodating frame 72;

The Y-axis moving structure is arranged in the hollow space in the middle of the lifting frame and is fixed on the bottom plate 11 or the vertical plate; the Y-axis direction driving motor 74 and the linkage structure are included, the linkage structure realizes the linkage of the accommodating frame 72 and the moving motor, and the accommodating frame 72 reciprocates along the Y axis along the supporting bracket of the accommodating frame 72 through the combination of the linkage structure and the moving motor.

Through the setting of above-mentioned scheme, realize the high uniformity of each rack through raising the frame, guaranteed the direction of motion that holds frame 72 through the setting of holding frame 72 support bracket that provides the guide track, and finally realize the motion of the Y axle direction that rack department provided through the cooperation of Y axle moving structure. The structural set-up pressure and space requirement pressure that rely on the merging structure 36 to accomplish 3-way movement is relieved. Because the movable structure of the Y axis is arranged at the position of the placing frame, the stability of movement in all directions is improved, and the space utilization efficiency is also improved.

In a more preferred embodiment, the accommodating frame 72 is provided with a second coupling structure 721 coupled to the linkage structure and moving together with the accommodating frame 72;

In a more preferred embodiment, the initial position of movement of the accommodating frame 72 is that the center of the first tube setting hole of the single group of tubes on the sample tube accommodating frame 31 and the projection point of the center of the gripping head on the accommodating frame platform are on the same X axis; the movement termination position of the accommodating frame 72 is that the center of the last tube body setting hole in the same column opposite to the first tube body setting hole of the single group of tube bodies and the projection point of the center of the gripping head on the placing frame platform are on the same X axis; the moving distance of the accommodating frame 72 is equal to the distance between the first tube setting hole and the center of the last tube setting hole. The arrangement is an optimal initial position arrangement, which can ensure that the rack meets the moving requirement with the shortest length requirement, and the shortest distance of the rack is the length of the accommodating rack 72 plus the distance between the first tube body arrangement hole and the center of the last tube body arrangement hole. More preferred embodiments are: the tube body of the pipette of the consumable rack is provided with holes, and the array mode of the tube body of the other racks and the starting position and the ending position of the tube body of the other racks on the Y axis are the same; the arrangement can basically ensure the uniformity of the tube body arrangement holes of each placing rack, and reduce the complexity of program arrangement.

In a more preferred embodiment, the lifting frame comprises 4 lifting columns 711, two lifting columns 711 are arranged on each side, a transverse connecting rod 712 for connecting the two lifting columns 711 on each side is arranged at the bottom, a fixing hole is arranged on the transverse connecting rod 712, and the fixing connection with the bottom plate 11 is realized through the fixing hole.

In a more preferred embodiment, the support bracket of the accommodating frame 72 is a support plate 73 of the accommodating frame 72, which can cover the space involved by the 4 lifting columns 711; and is connected with 4 lifting columns 711; the bottom of the accommodating frame 72 is provided with a surrounding structure 731 which is matched with the bearing plate 73 of the accommodating frame 72 in an extending manner, the bottom of the surrounding structure 731 is provided with a second combination structure 721 which is combined with the Y-axis moving structure, and the arrangement of the surrounding structure 731 can realize the track guiding function of the bearing plate 73 of the accommodating frame 72 and the combination with the Y-axis moving structure. More preferably, the surrounding structure 731 is disposed in the middle of the accommodating frame 72, and has a length equal to or less than the length of the accommodating frame 72 in the Y-axis direction. Or the bearing plate 73 of the accommodating frame 72 is provided with a guide groove along the Y-axis direction, the accommodating frame 72 is correspondingly provided with a guided structure entering the guide groove, but the accommodating frame 72 is still provided with a second combination structure 721 which is combined with the Y-axis moving structure and moves along with the accommodating frame 72; this way is also a way of setting up the second follower connection 721.

In a more preferred embodiment, a transition plate 75 capable of connecting 4 lifting columns 711 is arranged at the bottom of the supporting plate 73 of the accommodating frame 72, and the transition plate 75 is also connected with the supporting plate 73 of the accommodating frame 72 through a spacing structure such as (4 spacing columns); a linkage structure is arranged at the bottom of the transition plate 75, and a transition hole 751 is arranged on the transition plate 75 and used for guiding the combined structure from the transition plate 75 to the lower part of the transition plate 75 and connecting with the linkage structure below; by this arrangement, the problem that the range of the receiving frame 72 is related to the whole receiving frame 72 is achieved, if the linkage structure is arranged on the receiving frame 73 of the receiving frame 72, the problem is solved by extending the length of the receiving frame 73 of the receiving frame 72, but the device volume is increased as a whole, the space utilization is reduced, and the moving distance of the receiving frame 72 in the real moving process is only the distance between the first tube body setting hole and the center of the last tube body setting hole; therefore, by arranging the transition plate 75 and arranging the linkage structure on the transition plate 75, the space utilization rate can be effectively increased. More preferred embodiments are: the length of the transition hole 751 is also equal to or greater than the distance between the first pipe body setting hole and the center of the last pipe body setting hole.

More preferred embodiments, refer to fig. 11; the rotation axis of the Y-axis direction drive motor 74 is parallel to the Y-axis, and the linkage structure includes: the second rotating shaft 762 is connected with the rotating shaft of the motor, and the second rotating shaft 762 is also a screw rotating shaft; and a support plate 761 extending from the bottom of the transition plate 75 to the second rotating shaft 762; the second combination structure 721 is combined with the second rotating shaft 762. The second rotating shaft 762 rotates clockwise or anticlockwise to realize the reciprocating motion of the second combining structure 721, so as to drive the receiving frame 72 combined with the second rotating shaft to reciprocate. More preferred embodiments are: the effective working length of the second rotating shaft 762 is greater than or equal to the distance between the first tube setting hole and the center of the last tube setting hole, and the second combining structure 721 is respectively arranged at the two end parts of the second rotating shaft 762 when the receiving frame 72 moves to the initial position and the final position. In this way, the setting of the second rotating shaft 762 is achieved. The above-mentioned manner is a practical technical solution that the rotation axis of the Y-axis direction driving motor 74 is parallel to the Y-axis, and such technical solution needs to be considered in addition to the above technical points, and the overall length and the position of the Y-axis direction driving motor 74, the motor rotation axis and the second rotation axis 762 are set to ensure that they can be effectively placed in the hollow space in the middle of the lifting frame.

Or referring to fig. 9 and 10; it may also be preferable to implement the mode that the rotation axis of the Y-axis direction driving motor 74 is perpendicular to the Y-axis, specifically implemented as:

The linkage structure comprises a belt pulley III 763 connected with the rotating shaft of the Y moving motor, a belt pulley IV 764 which is separated from the belt pulley III 763 by a distance larger than the distance between the first pipe body setting hole and the center of the last pipe body setting hole, and a belt II which is arranged between the belt pulley III 763 and the belt pulley IV 764 and is used for realizing linkage; the center points of the third 763 and fourth 764 pulleys are arranged on the same Y-axis; the second combination structure 721 is combined with the second belt, and the second combination structure 721 and the second belt are not subjected to relative position change after combination; the third 763 and fourth 764 pulleys are fixedly arranged at the bottom of the transition plate 75. The second belt and the second combination 721 are realized by means of glue, rivets, or multi-layer fastening screws. The second belt driving engagement structure 721 moves between the first pulley 43 and the second pulley 44, so that the engagement of the second belt with the third pulley 763 and the fourth pulley 764 is not affected.

In a more preferred embodiment, the consumable rack 32 and the sample tube rack 31 do not contain other structures containing electricity, so that the movement can be realized in the above manner; the reagent rack 33 and the oscillation incubator rack 34 are both configured with circuit control, and the follow-up problem of the circuit and other pipelines needs to be considered in the process, so that the supporting plate 73 and the transition plate 75 of the accommodating rack 72 corresponding to the rack are correspondingly provided with a circuit and pipeline moving hole, and the circuit or pipeline is introduced into the hollow space through the circuit and pipeline moving hole and moves along with the movement of the accommodating rack 72. Only specific embodiments of sample tube holders 31 are shown in the drawings, but the combination of the written description and the drawings does not affect the understanding of the other holder embodiments.

Example 3

The manner in which the enrichment of multiple sets of sample tubes is accomplished in a single cycle is further defined on the basis of examples 1-2.

Arranging the sample tubes in groups, wherein the number of the sample tubes in one group is the same as the number of the centrifuge tubes in the centrifuge instrument 35; the oscillation incubation apparatus accommodates the sample tubes in groups, and the oscillation incubator can accommodate a plurality of groups of sample tubes of the whole device; the quantity of reagents and consumable materials required by the enrichment of exosomes is set according to the quantity of the integral sample tubes in the device;

Determining the number of groups of sample tubes in the exosome enrichment device according to the multiple relation of the first oscillation incubation time, the first centrifugation time and the sum of tube moving time of a single sample; dividing the integral multiple value of the sum of the first centrifugation time and the tube moving time by the first oscillation incubation time and adding the sample tube group number in a determining device; since the shaking incubation time is longer than the centrifugation time when the exosomes are enriched and the centrifugation apparatus 35 only contains the number of centrifuge tubes for which a set of samples are centrifuged, the number of sample tubes in the device is determined by dividing the first shaking incubation time by the integer multiple of the first centrifugation time; the device can complete exosome enrichment of a plurality of groups of samples in one large cycle, and exosome enrichment of more samples is performed under the condition of reducing the volume requirement.

For the core factors of limiting the size of the device when the size of the centrifugal machine is set, the conventional device equipment does not consider how to effectively relieve the factors of the centrifugal machine on the size of the device and the amount which can be borne by the device, and the above thought solves the constraint of the centrifugal equipment on the whole size of the device and the whole number of exosome enrichment carried out on the device by the way of arranging the sample tubes in groups, arranging the number of centrifugal tubes in the centrifugal instrument 35 to be the same as that of the single group of sample tubes and arranging various sample tubes; the exosome enrichment of more samples is completed in a shorter time on the premise of only one centrifuge.

More preferred embodiments are a set of sample tubes, and the consumable comprises a reaction tube and a pipette; the reaction tube and the sample tube are selected from the same tube body, and the arrangement mode of the single-row reaction tube is the same as that of the single-row sample tube; setting the number of columns of the reaction tubes according to the product of the number of times of the reaction tubes to be replaced and the number of groups of the sample tubes in the exosome enrichment process; the reagents are arranged in the reagent tubes, all the reagent tubes are arranged in rows, the reagent amount in each reagent tube meets the requirement of one row of sample tubes for finishing exosome enrichment, and all the reagents for finishing exosome enrichment are arranged in one row of reagent tubes;

The initial position and the end position of each group of sample tube setting holes and the reaction tube setting holes along the Y axis are the same as the initial position and the end position of each column of sample tube body setting holes in the oscillation incubation apparatus. Through the arrangement, the complexity of the procedure for moving the pipe body and the liquid can be effectively reduced.

More specifically, the method comprises the following steps: the single-row tube setting holes on the sample tube rack 31 and the tube setting holes corresponding to the single-row reaction tubes on the consumable rack 32 are identical in array mode of the single-row tube setting holes on the oscillation incubation rack, and the initial and final positions along the Y axis are identical; the aperture of the reagent hole of the reagent holding structure on the reagent holding frame 33 is different from the aperture of the hole of the tube body, but the circle center position array mode of each hole in a single row is the same, and more preferred embodiment, each row of reagent holes contains all reagents for completing enrichment, and the amount of the reagents in each reagent hole is equal to the amount of the reagents required for enriching a group of sample tubes. Reagent Kong Lieshu equals the number of sample tubes.

Performing a first centrifugation on the first set of samples, the first centrifuged samples being plasma from which separation has been completed; after the first centrifugation is completed, the corresponding supernatant or centrifugal solid is moved to an oscillation incubation process for oscillation incubation; starting a first centrifugation action of the second group of samples, suspending an oscillation incubation process after centrifugation, moving a corresponding supernatant or centrifugal solids of the second group of samples to the oscillation incubation process for oscillation incubation, repeating the actions until all groups of centrifugation actions are completed, waiting for the first group of samples to complete the first oscillation incubation action, and starting a centrifugation process of the next round and an oscillation incubation process of the next round; sequentially sending the supernatant or sediment corresponding to each group of sample tubes into an oscillation incubation process; until all groups were sent to the lower shake incubation procedure; repeating the process of the first round when the ratio of the oscillation incubation time of a certain round to the sum of the centrifugation time and the tube moving time of the corresponding round is greater than or equal to the ratio of the oscillation incubation time of the first round to the sum of the centrifugation time and the tube moving time of the first round; when the ratio of the oscillation incubation time of one wheel to the sum of the centrifugation time and the tube moving time of the corresponding wheel is smaller than the ratio of the oscillation incubation time of the first wheel to the sum of the centrifugation time of the first wheel and the tube moving time, the next centrifugation action of the previous group is firstly carried out, and then the centrifugation action of the next group of the current wheels is started; this method ensures that the incubation is performed in an efficient procedure of alternating centrifugation and shaking of groups of samples.

In a more preferred embodiment, a combining structure 36 is provided to combine the pipetting and pipetting actions, preferably in the centrifuge instrument 35 when a collision between pipetting and hydrodynamic movement in the centrifuge instrument 35 and pipetting and hydrodynamic movement in the shaking incubation instrument occurs. This approach may be in contact with reaction limiting problems due to only one set of sample tubes within the centrifuge instrument 35.

In a more preferred embodiment, the plasma-initiated exosome enrichment procedure according to the present invention is an exosome enrichment procedure comprising 7 reagents and corresponding 4 rounds of centrifugation and shaking incubation.

In a more preferred embodiment, 8 samples are arranged in each group, and the reagents with the largest demand among 7 reagents are contained in two reagent tubes; each reagent tube is provided with a sample size required by a half group of sample tubes; thus, 8 reagent tubes are arranged on each column of the reagent placing frame 33, and the reagent amount of each reagent in each column meets the enrichment requirement of a single group of sample tubes; the arrangement of the reagent tubes on the reagent rack is the same as that of the sample tubes, and the initial position and the end position of the Y axis of the arrangement are the same.

In a more preferred embodiment, after all the single groups of sample tubes on the sample tube rack 31 are removed, the program controls the display lamps of the groups to be on, so as to prompt that the next group of samples can be introduced and put in, and wait for reaction; in a more preferred embodiment, after the whole enrichment of the sample in the up-shift cycle is completed, the other color display lamp is controlled to be turned on, and at this time, all groups of sample tubes of a new cycle can be placed.

More preferred embodiments, the volume of the reaction liquid in the tube during centrifugation and shaking incubation is no more than one third of the volume of the tube; so as to prevent liquid from splashing due to shaking in the uncapping state.

Example 4

The process of enriching exosomes from blood source is carried out by using the above instrument: the sample tube and the reaction tube are a tube body, and the volume of the tube body is 1.5ml; the volume of the reaction liquid in the tube body in the centrifugal process and the shaking incubation process is not more than one third of the volume of the tube body; so as to prevent liquid from splashing due to shaking in the uncapping state.

Referring to fig. 12, a first round of centrifugal oscillation incubation operation: separating whole blood before entering the device to obtain blood plasma, transferring the blood plasma into the device, and centrifuging the blood plasma at a low temperature of 4 ℃ for 20min; the centrifugal force is 6000g; centrifuging and then taking supernatant into a reaction tube; the reaction tube moves from the consumable placement rack 32 to the oscillation incubation rack in advance; transferring the supernatant into a new tube, and then transferring the first reagent into the new tube, and incubating for 1h at 4 ℃ in an oscillating way;

Second round of centrifugation shake incubation operation: centrifuging at 4 ℃ for 20min, and discarding the supernatant; then, the tube body is transplanted to an oscillation incubation frame, and a second reagent is added for full dissolution; adding a reagent III, and incubating for 1h under normal temperature oscillation; adding a reagent IV, and incubating for 1h at normal temperature in an oscillating way;

third round of centrifugation and shaking incubation operation: centrifuging at 400g for 10min at 4 ℃; discarding the supernatant; adding a reagent five, mixing uniformly, and incubating for 10min at room temperature in an oscillating way;

Fourth centrifugal shaking incubation operation: centrifuging at 3000g for 10min at 4 ℃; transferring the supernatant into a new reaction tube; adding reagent six, mixing, adding reagent seven, and incubating at 4 ℃ for 10 mm.

Because the first centrifugation time is 20min; the first shaking incubation time is 1h; the single tube transfer and the liquid transfer time are controlled to be 5min; so 3 groups of sample tube settings were obtained using the relationship of the incubation time plus an integer multiple of the sum of centrifugation time and pipetting time.

Setting 3 groups of sample tubes, wherein 8 samples are arranged in each group; the centrifugal device 35 comprises 8 centrifugal tubes; because there are two passes of supernatant into the new tube, the column number of the reaction tube is twice that of the sample tube; 7 reagents are added in the process, and the process of taking the supernatant for 2 times is added; the number of pipettes is at least 9 times the number of sample tubes. The action of discarding the supernatant is performed by a waste liquid suction structure 6 which is provided above the centrifuge apparatus 35 and is not moved.

While the foregoing embodiments of the present invention have been described in terms of specific embodiments, it will be apparent to those skilled in the art that the foregoing embodiments are merely illustrative of some, but not all, of the present invention, and that other advantages and features of the present invention will be readily apparent to those of ordinary skill in the art from consideration of the specification. The invention may be embodied or applied in other specific forms without conflict, the present embodiments may be controlled by a person of ordinary skill in the art, without any exercise of inventive faculty, to obtain all other embodiments, based on the embodiments of the invention, from which the features of the embodiments described above may be combined.

Claims (10)

1. A blood-derived neurogenic exosome enrichment device comprises

The bottom plate is used for bearing instruments and consumables for automatically enriching exosomes;

The box cover is arranged on the bottom plate and forms a closed space with the bottom plate, and the instruments and consumables for automatically enriching exosomes are arranged in the closed space; the arrangement of the closed space enables all reagents and sample tubes to be operated in a non-cover state; it is characterized in that the method comprises the steps of,

The closed space is internally provided with:

The centrifugal instrument is used for centrifuging the sample tube in the exosome enrichment process and is arranged at a first edge position on one side of the bottom plate;

The sample tube placing rack is used for placing the sample tubes;

the consumable rack is used for placing the reaction tube and the pipette in the process and is divided into a reaction tube area and a pipette area;

The reagent placing rack is a low-temperature placing rack and is used for placing a plurality of reagents for automatically enriching exosomes;

the vibration incubator comprises a vibration incubator, a vibration incubator and a vibration incubator, wherein the vibration incubator is used for completing vibration incubation in the exosome enrichment process;

The moving structure is a combining structure, and the combining structure comprises a pipe body moving structure and a liquid moving structure which are combined; the combining structure controls the tube body moving structure and the liquid moving structure to move in the X-axis and Y-axis Z-axis three-dimensional directions;

a control structure for controlling the operation of the device;

the sample tube placing rack, the consumable placing rack, the reagent placing rack and the oscillating incubator placing rack have the same length in the Y-axis direction, and the heights in the Z-axis direction are uniform as a whole; sample tube rack, consumptive material rack, reagent rack, vibration incubator rack and centrifugal instrument are along the parallel straight line setting of X axis direction.

2. The apparatus of claim 1, wherein the moving structure comprises a combining structure comprising a pipe moving structure and a liquid moving structure that are combined; the pipe body moving structure and the liquid moving structure are provided with a Z-axis lifting structure; the device also comprises an X-axis moving structure and a Y-axis moving structure which control the merging structure and the sample tube placing frame, the consumable placing frame, the reagent placing frame and the oscillation incubator placing frame which are arranged below to move relatively in the X-axis and Y-axis directions;

The box cover is a five-sided wrapped box cover except the bottom, the front side surface of the box cover is provided with a plurality of box doors, and the box doors can be respectively opened to correspond to different inner structure areas; the mode can ensure that the relative replacement action is carried out on each internal structure, and other actions are not influenced;

The bottom plate is a rectangular plate, and centrifugal instrument, sample tube rack, consumptive material rack, reagent rack and vibration incubator rack all part all set up in the bottom top.

3. The device of claim 1, wherein the volume of a single sample tube is 2ml or less;

The sample tube placing rack is used for placing at least two groups of sample tubes, and the number of each group of sample tubes is consistent with that of the centrifugal tube holes in the centrifugal instrument; the number of reaction tubes or pipettes on the consumable rack is the number required for all groups of sample tubes; the reagent amount of the reagent placing rack is more than or equal to the reagent amount for completing enrichment of all groups of sample tubes on the sample tube placing rack; the vibration incubator rack is provided with vibration incubation holes the same as the sample tube rack in number;

the tube body setting holes on the sample tube rack and the tube body setting holes corresponding to the reaction tubes on the consumable rack are identical in array mode of the tube body setting holes on the oscillation incubation rack, and the initial and final positions along the Y axis are identical.

4. The device according to claim 1, wherein a longitudinal vertical plate is provided on the base plate, the longitudinal vertical plate being integrally provided along the X-axis direction; the longitudinal vertical plate is a plate with a bending angle;

A transverse vertical plate which is vertical to the longitudinal vertical plate and the bottom is arranged on the longitudinal vertical plate; the two transverse vertical plates are arranged, the first transverse vertical plate is arranged at a second edge position, and the second edge position and the first edge position are two edge positions opposite along the long edge of the bottom plate; the second transverse vertical plate is arranged at the bending position of the longitudinal vertical plate;

A horizontal plate which is perpendicular to the transverse vertical plate and the longitudinal vertical plate is arranged on the transverse vertical plate and the longitudinal vertical plate, and the longitudinal vertical plate extends to the upper part of the horizontal plate to divide the horizontal plate into a front area and a rear area;

Wherein, the transverse vertical plate and the longitudinal vertical plate and the horizontal plate divide the enclosed space into 4 areas; the method comprises the following steps of: the first region is a front lower region, the second region is a front upper region, the third region is a rear lower region, and the fourth region is a rear upper region.

5. The device of claim 4, wherein a first rotating shaft for controlling the merging structure to move along the X-axis direction of the merging structure is arranged in the second area, the first rotating shaft is a screw rotating shaft, the merging structure is provided with a first combining structure which is matched with the first rotating shaft, and the first combining structure is driven to reciprocate along the first rotating shaft by different rotating directions of the first rotating shaft; the first rotating shaft is connected with a belt pulley I through a first vertical transverse plate; the fourth area is provided with an X-axis direction driving motor, and a motor rotating shaft is connected with a belt pulley II through a first transverse vertical plate; the belt pulley I is connected with the belt pulley II through a belt I, so that the belt pulley I is driven by the X-axis driving motor to rotate, the belt pulley I is driven by the belt I to move, the belt I is driven by the belt II to rotate, and the belt pulley II is driven by the belt II to rotate; the rotation of the first rotating shaft drives the reciprocating motion of the merging structure.

6. The apparatus of claim 4, wherein the second region is a region meeting the arrangement of the rotating shaft, is smaller than the first region, the horizontal plate does not cover the working regions of the sample tube rack, the consumable rack, the reagent rack and the shaking incubator rack, and the merging structure is arranged in the region in front of the horizontal plate; the sample tube placing rack, the consumable placing rack, the reagent placing rack and the working area of the oscillating incubator placing rack extend into the centrifugal instrument from the front of the horizontal plate.

7. The device of claim 1, wherein the lowest end of the tube moving structure is a tube clamping head for clamping the tube, and the liquid moving structure comprises a pipetting head for taking out a pipette and sucking and pushing out the liquid; the waste collection structure is arranged at a second edge position of the bottom plate, the second edge position is opposite to the first edge position of the centrifugal device, and the waste collection structure and the first transverse vertical plate are arranged at different positions on the same transverse edge of the bottom; the waste collecting structure comprises a collecting opening, and when the combining structure moves to the second edge position of the first rotating shaft, the structure on the inner side of the tube body clamping head and the pipetting head moves to the upper part of the collecting opening.

8. The device of claim 1, wherein the lowest end of the tube moving structure is a tube clamping head for clamping the tube, and the liquid moving structure comprises a pipetting head for taking out a pipette and sucking and pushing out the liquid; the centrifugal instrument is provided with a first extending hole, wherein the first extending hole is a hole for allowing the pipe body clamping head and the liquid transferring head to extend into the pipe and liquid taking; when the merging structure moves to the first edge position of the first rotating shaft; the pipe body clamping head and the inner side structure of the pipetting head move to the upper part of the extending hole.

9. The apparatus of claim 1, wherein a waste liquid suction structure is disposed above the centrifugal structure, the waste liquid suction structure is fixedly disposed on the vertical plate, the waste liquid suction structure is only moved in the Z-axis direction, and a Z-axis moving structure is disposed; the waste liquid sucking structure comprises waste liquid sucking and releasing functions, and an extending hole II is arranged below the waste liquid sucking structure and is a hole for meeting the extending of the waste liquid sucking structure; a waste liquid collecting cavity is arranged in the centrifugal instrument, and a waste liquid collecting hole is arranged above the waste liquid collecting cavity; when the waste liquid suction structure sucks waste liquid from the sample tube, the waste liquid suction structure rotates through the centrifugal instrument to collect the waste liquid Kong Zhengchong and stretch into the second hole, so that the release of the waste liquid is completed.

10. The device of claim 1, wherein the sample tube holder, the consumable holder, the reagent holder, the shaking incubator holder, and the centrifuge apparatus are sequentially disposed along the longitudinal direction of the base plate from the second edge position to the first edge position.