CN214881524U - Automatic enrichment apparatus for neurogenic exosomes in blood - Google Patents
Automatic enrichment apparatus for neurogenic exosomes in blood Download PDFInfo
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- CN214881524U CN214881524U CN202120481103.XU CN202120481103U CN214881524U CN 214881524 U CN214881524 U CN 214881524U CN 202120481103 U CN202120481103 U CN 202120481103U CN 214881524 U CN214881524 U CN 214881524U
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Abstract
An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame at the bottom and a movable operation frame above the reaction frame; the control structure controls the operation frame to run according to a preset track and controls the reaction frame to react according to a set program; the reaction frame is provided with an oscillation incubation structure, a centrifugal structure, a reagent placing structure, a consumable material placing structure, a discarded object placing structure, a sample information identification structure and an enrichment sample collection structure after reaction, wherein the oscillation incubation structure, the centrifugal structure, the reagent placing structure, the consumable material placing structure, the discarded object placing structure, the sample information identification structure and the enrichment sample collection structure are required for realizing exosome enrichment; the operation frame is provided with a pipe body moving structure for moving the pipe body among different structures, and a liquid taking and adding structure for transferring liquid in the whole process is realized; in addition, an EP tube marking and identifying structure used when the EP tube is used for the first time is arranged on the reaction frame or the operation frame; the operation frame is controlled by the control structure to move to clamp the sampling tube and various liquids, the samples are automatically enriched according to a set program, and the whole process can effectively enrich the neurogenic exosomes.
Description
Technical Field
The invention belongs to the technical field of medical instruments, and particularly relates to an automatic enrichment instrument for exosome enrichment; in particular to an automatic enriching apparatus for neurogenic exosomes in blood.
Background
Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheath, which worsen over time and present with dysfunction. Such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and prion diseases, among others. At present, the definite clinical diagnosis of neurodegenerative diseases depends on PET (positron emission tomography), and the diseases are often developed to the stage of non-treatment and non-retrieval when pathological changes occur.
The diagnosis of the diseases can be advanced by detecting the related biomarkers through the cerebrospinal fluid, but the sampling mode of the cerebrospinal fluid has large wound on a human body and low willingness of a patient; rarely have the patient and will detect in advance before the symptom appears, this kind of detection also often just goes on after the patient appears the symptom, and the collection degree of difficulty of cerebrospinal fluid is big moreover, and the risk is high, and is very high to operator's requirement, also hardly becomes the detection mode that the patient sickened the risk of a conventional detectable patient.
There is therefore a need to find a method that is simple to collect and easy to detect, and that preferably allows a single screening in a normal annual physical examination. With the intensive research of exosome, it is found that the neurogenic exosome in blood can be used as a sample to detect the relevant indexes of neurodegenerative diseases, so that the diagnosis of the diseases can be greatly advanced, and the compliance of the sample to a subject is stronger compared with cerebrospinal fluid.
However, the neurogenic exosomes in blood need to be obtained by enrichment. Although the current technology can obtain the samples, the samples are obtained through manual operation, the whole operation process comprises a plurality of processes such as cooling, centrifuging, oscillating, sample adding, blowing and beating, the time consumption is long, an operator needs to perform timing, the whole process consumes a large amount of manpower and is long in time, and the pure manual operation can easily cause wrong conclusions due to sample errors in the operation process, so that the method cannot be an effective and rapid popularization mode and can effectively obtain the conclusions.
If an automatic device is available to complete the above process, the neurogenic exosomes of the subject can be rapidly and effectively enriched, and the relevant information can be detected, so that the possibility of the risk of the disease of the subject can be known in advance, and the subject can be prevented in advance. By the popularization and the application of the detection mode, the occurrence of excessive neurodegenerative diseases along with the aging problem of the population can be greatly reduced.
The invention provides an automatic enrichment apparatus for neurogenic exosomes in blood, aiming at the problem that no equipment for effectively and quickly enriching blood neurogenic exosomes exists in the prior art.
Disclosure of Invention
An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame at the bottom and a movable operation frame above the reaction frame; the control structure controls the operation frame to run according to a preset track and controls the reaction frame to react according to a set program; the device is characterized in that the reaction frame is provided with an oscillation incubation structure, a centrifugal structure, a reagent placing structure, a consumable material placing structure, a waste placing structure, a sample information identification structure and an enrichment sample collection structure after reaction, wherein the oscillation incubation structure, the centrifugal structure, the reagent placing structure, the consumable material placing structure, the waste placing structure, the sample information identification structure and the enrichment sample collection structure are required for realizing exosome enrichment; the operation frame is provided with a pipe body moving structure for moving the pipe body among different structures, and a liquid taking and adding structure for transferring liquid in the whole process is realized; in addition, an EP tube marking and identifying structure used when the EP tube is used for the first time is arranged on the reaction frame or the operation frame; the equipment also comprises a storage module capable of storing information, a control structure controls the oscillation speed and the amplitude of the oscillation incubation structure, and controls the temperature required by the corresponding step of the oscillation incubation structure; the control structure controls and monitors the reagent amount of the reagent placing structure, and prompts replacement after no reagent exists; the control structure also controls the centrifugal parameters of the centrifugal structure; the control structure monitors and records the information of the sample in the corresponding placing hole of the sample placing structure; the control structure controls the sample information to identify the sample tube information and stores the sample tube information in the storage module; the control structure controls the liquid taking and adding pipe to move to carry out the liquid taking and adding process, controls the pipe body moving structure to grab the corresponding pipe body and move to the corresponding area of the corresponding next structure, and controls the EP pipe marking and identifying structure to scan or identify the information on the EP pipe and correspond to the corresponding sample pipe information; ensuring that the patient information pair is confused or lost during the moving process; the control structure controls the placement of the last EP tube into the enriched sample collection structure.
During specific operation, the control structure controls the information identification structure to firstly identify the information code of the sample tube, store the information code into a storage unit of the equipment, and sequentially set the information code into the sample placement structure after identification; then, grabbing sample tubes in the sample placing structure to a next processing structure oscillation incubation structure according to a set sequence through a tube body moving structure on the operation frame, moving the sample tubes to a consumable placing structure according to control setting after entering the oscillation incubation structure, installing corresponding consumable materials, moving the consumable materials to a reagent placing structure, moving the consumable materials to a corresponding sample tube placing position of the oscillation incubation structure to add the reagent after obtaining the corresponding reagent, moving the liquid tubes to a waste placing structure after adding the reagent, and discarding the waste consumable materials in the waste placing structure after the liquid tubes leave the waste placing structure and move to the waste placing structure; after the reagent is added, the control structure controls the oscillation incubation structure to carry out oscillation or incubation treatment, and the steps of adding the reagent in the oscillation incubation treatment process are all carried out according to the steps; when a sample tube needs to be moved into a centrifugal structure, a control structure controls a tube body moving structure to grab the sample tube to move and place the sample tube into the centrifugal structure for centrifugation, if liquid needs to be added after centrifugation, the reagent is added according to the liquid taking and adding steps, when supernatant needs to be reserved and moved into an EP tube, the EP tube is placed into the structure of the next step, information on the EP tube is scanned or identified through an EP tube marking and identifying structure and corresponds to the information of the corresponding sample tube, then the liquid in the sample tube is moved into the corresponding EP tube by using the liquid taking and adding structure, when the EP tube is in an oscillation incubation structure, oscillation incubation is carried out according to the oscillation incubation process, the reagent is added when the reagent needs to be added, and when the sample tube needs to be centrifuged again, the tube body moving structure is used for moving the sample tube into the centrifugal structure; when the sediment needs to be reserved after the centrifugation is finished, the control structure controls the liquid taking and adding structure to draw out the supernatant from the EP pipe and discard the supernatant in the discarded object placing structure; and (4) after the enrichment is completed under the control of the control structure according to the step of exosome enrichment, placing the enriched EP tube closed tube into an enrichment sample collection structure.
Further, a plurality of oscillation incubation structures, a centrifugal structure, a reagent placing structure, a consumable material placing structure and a waste material placing structure are arranged according to the operation steps; therefore, the moving distance of the operating frame above the operating frame can be reduced, and the continuity of the whole automatic process is improved.
Further, sample or EP pipe need add the reagent step occasionally at the oscillation structure stage of hatching, and the structure is placed to the other reagent that sets up of structure is hatched in the oscillation that corresponds and corresponds, and the structure is placed to the consumptive material, and the structure is placed to the abandonment thing, conveniently draws materials nearby and abandons nearby.
Or, in the case of only carrying out sample enrichment for one batch in one operation, when the structural shapes of the sample tube and the EP tube are the same, 1 oscillation incubation structure and 1 centrifugal structure are arranged in the whole process; the whole device is few in structure and small in occupied space, and the device can be used in a laboratory mainly aiming at the enrichment process of relatively small samples.
Or, in the case of only performing sample enrichment of one batch in one operation, when the shapes of the sample tube and the EP tube are different, the minimum number of oscillation incubation structures and centrifugation structures are set according to the requirements of the tubes of different shapes, and only one batch of samples are enriched in one process of the whole device.
Further, only carry out the condition of a batch sample enrichment to a process, set up a reagent and place the structure, the consumptive material is placed the structure, and the abandonment is placed the structure, and all reagents that set up the exosome enrichment respectively in unison, the consumptive material reaches abandons the structure, can further reduce equipment occupation space, and because overall structure is less, the handling frame removes and can not consume too much time.
Further, the handling frame sets up on setting up the top, sets up the top for the relative reaction frame position of reaction frame top does not change sets up the top, sets up the top and sets up the removal track that guarantees that the handling frame can move arbitrary structure top and carry out corresponding operation.
Further, the handling frame is an integral frame, the liquid taking and feeding structure and the pipe body moving structure are arranged on the handling frame, and the liquid taking and feeding structure and the pipe body moving structure can move up and down on the handling frame, so that one structure can play a role.
Or two operation frames are arranged, namely a liquid taking and filling operation frame and a pipe body moving operation frame; when the operation is performed, the operation frames move to the positions above the corresponding structures respectively, and when one operation frame acts, the other operation frame moves to the position where the other operation frame cannot be interfered through the moving track.
Further, get liquid feeding structure and body and remove the structural operating head that sets up the same figure, can guarantee like this to press from both sides the sample pipe of getting the same figure to reagent is added in correspondingly.
Furthermore, the reagent placing structure is provided with liquid taking ports corresponding to a single reagent, the number of the liquid taking ports is equal to that of the operating heads of the liquid taking and adding structure, and the position relationship of the liquid taking ports is consistent with that of the operating heads; the consumable placing structure is provided with material taking ports with the number equal to that of the operating heads of the liquid taking and adding structure corresponding to a single consumable; and the position relation of the material taking port is consistent with the position relation of the operating head.
Furthermore, the number of the single-column placing holes is integral multiple of the number of the operating heads, or the number of the columns of the placing holes is consistent with the number of the operating heads, so that the sample tubes can be obtained according to an effective sequence.
Furthermore, a fault alarm structure is arranged between each structure and the control structure, and when the corresponding fault alarm structure sends out an alarm signal, the corresponding structure is prompted to send out a fault. Or the control structure is also connected with a display structure, the display structure displays the alarm of the corresponding alarm structure and prompts the corresponding structure fault to be maintained, and the alarm is timely given out when the complex structure is in a problem.
Furthermore, the reaction times corresponding to the reagent amounts of any two different reagents in the reagent placing structure are equal, and when the times are reached, prompting is carried out or structural display is displayed for replacement.
Further, the reaction times that the consumptive material volume of two arbitrary different consumptive materials in the structure is placed to the consumptive material corresponds also equals, and perhaps the consumptive material volume of every kind of consumptive material is the same with reagent reaction times, and convenient whole is changed reagent and consumptive material.
Further, the discard placing structure is divided into a consumable discarding part and a liquid discarding part; respectively processing the waste consumables and the liquid.
Further, the volume that the structure was placed to abandonment held the abandonment equals to hold the required space of change reagent consumptive material once, can change along with reagent consumptive material piece, finally can reduce the control degree of difficulty, increase efficiency.
Further, the reagent placing structure, the consumable placing structure and the discard placing structure are arranged below the middle setting plate of the reaction frame, and the combination is arranged below the setting plate, so that the replacement is convenient.
Furthermore, the EP pipe mark and the identification structure are arranged on the pipe body moving structure, and different identification structures which can be in one-to-one correspondence are arranged at the top of the EP pipe; the EP tube is scanned and identified at the upper part and corresponds to the corresponding sample tube information, so that the aim of information matching is fulfilled, and the process is simple and convenient.
Further, because the entire enrichment process comprises multiple shaking incubations and centrifugation processes, each process comprises one shaking incubation and centrifugation step; dividing a reaction frame of the whole device into a plurality of corresponding reaction areas according to the times of the oscillating incubation and the centrifugation process; further, every region that corresponds all sets up the vibration and incubate the structure, centrifugal structure, and the structure is placed to reagent, and the structure is placed to the consumptive material, and the structure is placed to the abandonment.
Furthermore, a set of operation frame with a liquid taking and adding structure and a pipe body moving structure is arranged above each reaction area. Can realize the liquid of getting of flow like this and press from both sides and get the body, can not eat the problem that has the use conflict.
Further, the removal track of handling frame is for can satisfying the handling frame and remove the track that realizes getting liquid and press from both sides and get the body.
Further, the movement track is provided in a divided manner so as to be able to move in the local area and to obtain a sample or an EP tube in the upward movement area.
Further, the enrichment sample collection structure is provided with an EP tube consumable material placement structure, or the EP tube consumable material placement structure is arranged in the other nearest reaction area; when going on to last step, move the EP pipe to enrichment sample collection domain through body moving structure, later with the supernatant that the enrichment is accomplished move to the EP pipe through getting liquid filling liquid structure and collect, later detect.
Compared with the prior art, the technical scheme of the invention can well solve the problem of exosome enrichment in the prior art, can be automatically completed, can well popularize exosome detection, can become the effect of diagnosing neurodegenerative diseases in advance and intervening treatment by detecting the condition of neurogenic exosomes in blood in advance if the exosome detection is suitable for future popularization, solves the problem that the Chinese population suffers from the neurodegenerative diseases along with the aging of the population, and reduces the pressure of the whole society.
Drawings
FIG. 1 is a schematic view of the overall structure of the present invention;
FIG. 2 is a schematic top view of a reaction frame according to the present invention;
FIG. 3 is a side view of a portion of the handling frame of the present invention;
FIG. 4 is a schematic diagram of the overall structure of the present invention including only one reaction region;
FIG. 5 is a schematic view of the structure of the working flow of the apparatus of the present invention;
FIG. 6 is a schematic structural view of the apparatus of the present invention in a modular structure;
in the figure, 1, a reaction frame; 11. oscillating the incubation structure; 12. a centrifugal structure; 13. a reagent placement structure; 14. a consumable material placement structure; 15. a discard placement structure; 151. a consumable disposal part; 152. a liquid disposal portion; 16. a sample placement structure; 17. a sample information identification structure; 18. an enrichment sample collection structure; 2. an operation frame; 21. a pipe body moving structure; 22. a liquid taking and adding structure; 23. an EP tube marking and identification structure; 24. setting a top; 25. an operating head; 26. a moving track; 3. a control structure; 4. a storage module; 5. and a fault alarm structure.
Detailed Description
Example 1 automatic enrichment apparatus for neurogenic exosomes in blood
An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame 1 at the bottom and an operation frame 2 which can move above the reaction frame; and a control structure 3 for controlling the operation frame 2 to run according to a preset track and the reaction frame 1 to react according to a set program; the reaction frame 1 is provided with an oscillation incubation structure 11, a centrifugal structure 12, a reagent placing structure 13, a consumable material placing structure 14, a discarded object placing structure 15, a sample placing structure 16, a sample information identification structure 17 and an enrichment sample collection structure 18 after reaction, wherein the oscillation incubation structure 11, the centrifugal structure 12, the reagent placing structure 13, the consumable material placing structure 14, the discarded object placing structure 15, the sample placing structure 16 and the sample information identification structure 17 are required for realizing exosome enrichment;
the operation frame 2 is provided with a pipe body moving structure 21 for moving the pipe body among different structures and a liquid taking and adding structure 22 for transferring liquid in the whole process; in addition, an EP tube marking and identifying structure 23 for the first use of the EP tube is arranged on the reaction frame 1 or the operation frame 2; the device also comprises a storage module 4 capable of storing information, wherein the control structure 3 controls the oscillation speed and the amplitude of the oscillation incubation structure 11 and controls the temperature of the oscillation incubation structure 11 required by the corresponding step; the control structure 3 controls and monitors the reagent amount of the reagent placing structure 13 and prompts replacement after no reagent exists; the control structure 3 also controls the centrifugation parameters of the centrifugation structure 12; the control structure 3 monitors and records the information of the sample in the corresponding placing hole of the sample placing structure 16; the control structure 3 controls the sample information to identify the sample tube information and stores the sample tube information in the storage module 4; the control structure 3 controls the liquid taking and adding pipe to move to carry out the liquid taking and adding process, the control structure 3 controls the pipe body moving structure 21 to grab the corresponding pipe body and move to the corresponding area of the corresponding next structure, and the control structure 3 controls the EP pipe marking and identifying structure 23 to scan or identify the information on the EP pipe and correspond to the corresponding sample pipe information; ensuring that the patient information pair is confused or lost during the moving process; the control structure 3 controls the placement of the last EP tube into the enriched sample collection structure 18.
During specific operation, the control structure 3 controls the information identification structure to firstly identify the information code of the sample tube, store the information code into a storage unit of the equipment, and sequentially arrange the information code into the sample placement structure 16 after identification; then, the sample tubes in the sample placing structure 16 are grabbed by the tube body moving structure 21 on the operation frame 2 according to a set sequence and reach the next processing structure oscillation incubation structure 11, after entering the oscillation incubation structure 11, the liquid taking and adding structure 22 moves to the consumable material placing structure 14 according to control setting, corresponding consumable materials are installed and then move to the reagent placing structure 13, after corresponding reagents are obtained, the corresponding sample tubes are moved to the corresponding sample tube placing positions of the oscillation incubation structure 11 for reagent addition, the liquid taking and adding structure 22 leaves and moves to the discarded object placing structure 15 after the reagents are added, and the discarded consumable materials are discarded in the discarded object placing structure 15; after the reagent is added, the control structure 3 controls the oscillation incubation structure 11 to carry out oscillation or incubation treatment, and the steps of adding the reagent in the oscillation incubation treatment process are all reagent adding according to the steps; when a sample tube needs to be moved into the centrifugal structure 12, the control structure 3 controls the tube body moving structure 21 to grab the sample tube to move and place the sample tube into the centrifugal structure 12 for centrifugation, if liquid needs to be added after centrifugation, the reagent is added according to the liquid taking and adding steps, when supernatant needs to be reserved and moved into an EP tube, the EP tube is placed into the next step structure, information on the EP tube is scanned or identified through the EP tube marking and identifying structure 23 and corresponds to the corresponding sample tube information, then the liquid taking and adding structure 22 is used for moving the liquid in the sample tube into the corresponding EP tube, when the EP tube is in the oscillation incubation structure 11, oscillation incubation is carried out according to the oscillation incubation process, the reagent is added when the reagent needs to be added, and when the sample tube needs to be centrifuged again, the tube body moving structure 21 is used for moving the centrifugal structure 12; when the sediment needs to be reserved after the centrifugation is finished, the control structure 3 controls the liquid taking and adding structure 22 to draw the supernatant out of the EP pipe and discard the supernatant in the discarded object placing structure 15; after the enrichment is completed under the control of the control structure 3 according to the step of exosome enrichment, the enriched EP tube closed is placed into the enriched sample collection structure 18.
Sample or EP pipe need add the reagent step when 11 stages are hatched in the oscillation, incubate the structure 11 side at the oscillation and set up corresponding reagent and place structure 13, and the structure 14 is placed to the consumptive material, and the structure 15 is placed to the abandonment thing, conveniently draws materials nearby and abandons nearby.
In the case of only carrying out sample enrichment for one batch in one operation, when the structural shapes of the sample tube and the EP tube are the same, 1 oscillation incubation structure 11 and 1 centrifugal structure 12 are arranged in the whole process; the whole device is few in structure and small in occupied space, and the device can be used in a laboratory mainly aiming at the enrichment process of relatively small samples.
To the condition that only carry out a batch sample enrichment to a process, set up a reagent and place structure 13, consumptive material and place structure 14, abandonment thing and place structure 15, set up all reagents that exosome enriched respectively in unison, the consumptive material reaches abandonment structure, can further reduce equipment occupation space, and because overall structure is less, the handling frame 2 removes and can not consume too much time.
The handling frame 2 is arranged on the setting top 24, the setting top 24 is the setting top 24 which is arranged above the reaction frame 1 and does not change relative to the position of the reaction frame 1, and the setting top 24 is provided with a moving track 26 which ensures that the handling frame 2 can move to any structure and carry out corresponding operation.
The operation frame 2 is an integral frame, on which a liquid taking and adding structure 22 and a tube body moving structure 21 are arranged, and the liquid taking and adding structure 22 and the tube body moving structure 21 can move up and down on the operation frame 2, so that one structure can play its own role.
Get liquid and add liquid structure 22 and set up the operating head 25 of the same number on the body moves the structure 21, can guarantee like this to press from both sides and get the sample pipe of the same number to correspondingly carry out reagent and add.
The reagent placing structure 13 is provided with liquid taking ports corresponding to a single reagent, the number of the liquid taking ports is equal to that of the operating heads 25 of the liquid taking and adding structure 22, and the position relationship of the liquid taking ports is consistent with that of the operating heads 25; the consumable material placing structure 14 is provided with material taking ports with the number equal to that of the operating heads 25 of the liquid taking and adding structure 22 corresponding to a single consumable material; and the position relation of the material taking port is consistent with the position relation of the operating head 25.
The number of the single-column placing holes is integral multiple of the number of the operating heads 25, or the number of the columns of the placing holes is consistent with the number of the operating heads 25, so that sample tubes can be obtained according to an effective sequence.
The reagent placing structure 13, the consumable placing structure 14 and the discard placing structure 15 are arranged under the middle setting plate of the reaction frame 1, and the combination is arranged under the setting plate, so that the replacement is convenient.
The EP pipe marking and identifying structure 23 is arranged on the pipe body moving structure 21, and different identifying structures which can be in one-to-one correspondence are arranged at the top of the EP pipe; the EP tube is scanned and identified at the upper part and corresponds to the corresponding sample tube information, so that the aim of information matching is fulfilled, and the process is simple and convenient.
The enrichment sample collection structure 18 is provided with an EP tube consumable material placement structure 14; when the final step is reached, the EP tube is moved to the enriched sample collection structure 18 domain by the tube body moving structure 21, and then the enriched supernatant is moved to the EP tube for collection by the liquid taking and adding structure 22, and then detection is carried out.
An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame 1 at the bottom and an operation frame 2 which can move above the reaction frame; and a control structure 3 for controlling the operation frame 2 to run according to a preset track and the reaction frame 1 to react according to a set program; the device is characterized in that the reaction frame 1 is provided with an oscillation incubation structure 11, a centrifugal structure 12, a reagent placing structure 13, a consumable material placing structure 14, a discarded object placing structure 15, a sample placing structure 16, a sample information identification structure 17 and an enrichment sample collection structure 18 which are required for realizing exosome enrichment; the operation frame 2 is provided with a pipe body moving structure 21 for moving the pipe body among different structures and a liquid taking and adding structure 22 for transferring liquid in the whole process; in addition, an EP tube marking and identifying structure 23 for the first use of the EP tube is arranged on the reaction frame 1 or the operation frame 2; the device also comprises a storage module 4 capable of storing information, wherein the control structure 3 controls the oscillation speed and the amplitude of the oscillation incubation structure 11 and controls the temperature of the oscillation incubation structure 11 required by the corresponding step; the control structure 3 controls and monitors the reagent amount of the reagent placing structure 13 and prompts replacement after no reagent exists; the control structure 3 also controls the centrifugation parameters of the centrifugation structure 12; the control structure 3 monitors and records the information of the sample in the corresponding placing hole of the sample placing structure 16; the control structure 3 controls the sample information to identify the sample tube information and stores the sample tube information in the storage module 4; the control structure 3 controls the liquid taking and adding pipe to move to carry out the liquid taking and adding process, the control structure 3 controls the pipe body moving structure 21 to grab the corresponding pipe body and move to the corresponding area of the corresponding next structure, and the control structure 3 controls the EP pipe marking and identifying structure 23 to scan or identify the information on the EP pipe and correspond to the corresponding sample pipe information; ensuring that the patient information pair is confused or lost during the moving process; the control structure 3 controls the placement of the last EP tube into the enriched sample collection structure 18.
During specific operation, the control structure 3 controls the information identification structure to firstly identify the information code of the sample tube, store the information code into a storage unit of the equipment, and sequentially arrange the information code into the sample placement structure 16 after identification; then, the sample tubes in the sample placing structure 16 are grabbed by the tube body moving structure 21 on the operation frame 2 according to a set sequence and reach the next processing structure oscillation incubation structure 11, after entering the oscillation incubation structure 11, the liquid taking and adding structure 22 moves to the consumable material placing structure 14 according to control setting, corresponding consumable materials are installed and then move to the reagent placing structure 13, after corresponding reagents are obtained, the corresponding sample tubes are moved to the corresponding sample tube placing positions of the oscillation incubation structure 11 for reagent addition, the liquid taking and adding structure 22 leaves and moves to the discarded object placing structure 15 after the reagents are added, and the discarded consumable materials are discarded in the discarded object placing structure 15; after the reagent is added, the control structure 3 controls the oscillation incubation structure 11 to carry out oscillation or incubation treatment, and the steps of adding the reagent in the oscillation incubation treatment process are all reagent adding according to the steps; when a sample tube needs to be moved into the centrifugal structure 12, the control structure 3 controls the tube body moving structure 21 to grab the sample tube to move and place the sample tube into the centrifugal structure 12 for centrifugation, if liquid needs to be added after centrifugation, the reagent is added according to the liquid taking and adding steps, when supernatant needs to be reserved and moved into an EP tube, the EP tube is placed into the next step structure, information on the EP tube is scanned or identified through the EP tube marking and identifying structure 23 and corresponds to the corresponding sample tube information, then the liquid taking and adding structure 22 is used for moving the liquid in the sample tube into the corresponding EP tube, when the EP tube is in the oscillation incubation structure 11, oscillation incubation is carried out according to the oscillation incubation process, the reagent is added when the reagent needs to be added, and when the sample tube needs to be centrifuged again, the tube body moving structure 21 is used for moving the centrifugal structure 12; when the sediment needs to be reserved after the centrifugation is finished, the control structure 3 controls the liquid taking and adding structure 22 to draw the supernatant out of the EP pipe and discard the supernatant in the discarded object placing structure 15; after the enrichment is completed under the control of the control structure 3 according to the step of exosome enrichment, the enriched EP tube closed is placed into the enriched sample collection structure 18.
Sample or EP pipe need add the reagent step when 11 stages are hatched in the oscillation, incubate the structure 11 side at the oscillation and set up corresponding reagent and place structure 13, and the structure 14 is placed to the consumptive material, and the structure 15 is placed to the abandonment thing, conveniently draws materials nearby and abandons nearby.
In the case of only performing sample enrichment of one batch in one operation, when the shapes of the sample tube and the EP tube are different, the minimum number of the oscillation incubation structures 11 and the centrifugation structures 12 are arranged according to the requirements of the tubes with different shapes, and only one batch of samples are enriched in one process of the whole equipment.
To the condition that only carry out a batch sample enrichment to a process, set up a reagent and place structure 13, consumptive material and place structure 14, abandonment thing and place structure 15, set up all reagents that exosome enriched respectively in unison, the consumptive material reaches abandonment structure, can further reduce equipment occupation space, and because overall structure is less, the handling frame 2 removes and can not consume too much time.
The handling frame 2 is arranged on the setting top 24, the setting top 24 is the setting top 24 which is arranged above the reaction frame 1 and does not change relative to the position of the reaction frame 1, and the setting top 24 is provided with a moving track 26 which ensures that the handling frame 2 can move to any structure and carry out corresponding operation.
The operation frame 2 is an integral frame, on which a liquid taking and adding structure 22 and a tube body moving structure 21 are arranged, and the liquid taking and adding structure 22 and the tube body moving structure 21 can move up and down on the operation frame 2, so that one structure can play its own role.
Another embodiment of the handling frame 2 is: the two operation frames 2 are respectively a liquid taking and adding operation frame 2 and a tube body moving operation frame 2; when the operation is performed, the operation frames are respectively moved to the upper part of the corresponding structures, and when one operation frame 2 is operated, the other operation frame 2 is moved to a position where the other operation frame 2 is not interfered by the moving rail 26.
Get liquid and add liquid structure 22 and set up the operating head 25 of the same number on the body moves the structure 21, can guarantee like this to press from both sides and get the sample pipe of the same number to correspondingly carry out reagent and add.
The reagent placing structure 13 is provided with liquid taking ports corresponding to a single reagent, the number of the liquid taking ports is equal to that of the operating heads 25 of the liquid taking and adding structure 22, and the position relationship of the liquid taking ports is consistent with that of the operating heads 25; the consumable material placing structure 14 is provided with material taking ports with the number equal to that of the operating heads 25 of the liquid taking and adding structure 22 corresponding to a single consumable material;
and the position relation of the material taking port is consistent with the position relation of the operating head 25.
The number of the single-column placing holes is integral multiple of the number of the operating heads 25, or the number of the columns of the placing holes is consistent with the number of the operating heads 25, so that sample tubes can be obtained according to an effective sequence.
And a fault alarm structure 5 is arranged between each structure and the control structure 3, and when the corresponding fault alarm structure 5 sends an alarm signal, the corresponding structure is prompted to send a fault. Or, the control structure 3 is also connected with a display structure, the display structure displays the corresponding alarm structure to give an alarm, and prompts the corresponding structure to break down for maintenance, and the alarm is given in time when the complex structure is in failure.
The reaction times corresponding to the reagent amounts of any two different reagents in the reagent holding structure 13 are equal, and when the times are reached, a prompt is given or a display on the display structure is displayed for replacement. The reaction number of times that the consumptive material volume of two arbitrary different consumptive materials in the structure 14 is placed to the consumptive material corresponds also equals, and perhaps the consumptive material volume of every kind of consumptive material is the same with reagent reaction number of times, makes things convenient for whole reagent and consumptive material to change. The discard placing structure 15 is divided into a consumable discarding part 151 and a liquid discarding part 152; respectively processing the waste consumables and the liquid. The volume that abandonment thing placement structure 15 held the abandonment thing equals to hold the required space of once changing the reagent consumptive material, can change along with reagent consumptive material piece, finally can reduce the control degree of difficulty, increase efficiency.
The reagent placing structure 13, the consumable placing structure 14 and the discard placing structure 15 are arranged under the middle setting plate of the reaction frame 1, and the combination is arranged under the setting plate, so that the replacement is convenient.
The EP pipe marking and identifying structure 23 is arranged on the pipe body moving structure 21, and different identifying structures which can be in one-to-one correspondence are arranged at the top of the EP pipe; the EP tube is scanned and identified at the upper part and corresponds to the corresponding sample tube information, so that the aim of information matching is fulfilled, and the process is simple and convenient.
Enrichment sample collection structure 18 sets up EP pipe consumptive material and places structure 14, when going on to last step, removes structure 21 through the body and removes the EP pipe to enrichment sample collection structure 18 domain, and the later supernatant that will enrich is collected in moving to the EP pipe through getting liquid feeding structure 22, later detects.
Embodiment 3 an automatic enriching apparatus for neurogenic exosomes in blood
An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame 1 at the bottom and an operation frame 2 which can move above the reaction frame; and a control structure 3 for controlling the operation frame 2 to run according to a preset track and the reaction frame 1 to react according to a set program; the device is characterized in that the reaction frame 1 is provided with an oscillation incubation structure 11, a centrifugal structure 12, a reagent placing structure 13, a consumable material placing structure 14, a discarded object placing structure 15, a sample placing structure 16, a sample information identification structure 17 and an enrichment sample collection structure 18 which are required for realizing exosome enrichment; the operation frame 2 is provided with a pipe body moving structure 21 for moving the pipe body among different structures and a liquid taking and adding structure 22 for transferring liquid in the whole process; in addition, an EP tube marking and identifying structure 23 for the first use of the EP tube is arranged on the reaction frame 1 or the operation frame 2; the device also comprises a storage module 4 capable of storing information, wherein the control structure 3 controls the oscillation speed and the amplitude of the oscillation incubation structure 11 and controls the temperature of the oscillation incubation structure 11 required by the corresponding step; the control structure 3 controls and monitors the reagent amount of the reagent placing structure 13 and prompts replacement after no reagent exists; the control structure 3 also controls the centrifugation parameters of the centrifugation structure 12; the control structure 3 monitors and records the information of the sample in the corresponding placing hole of the sample placing structure 16; the control structure 3 controls the sample information to identify the sample tube information and stores the sample tube information in the storage module 4; the control structure 3 controls the liquid taking and adding pipe to move to carry out the liquid taking and adding process, the control structure 3 controls the pipe body moving structure 21 to grab the corresponding pipe body and move to the corresponding area of the corresponding next structure, and the control structure 3 controls the EP pipe marking and identifying structure 23 to scan or identify the information on the EP pipe and correspond to the corresponding sample pipe information; ensuring that the patient information pair is confused or lost during the moving process; the control structure 3 controls the placement of the last EP tube into the enriched sample collection structure 18.
During specific operation, the control structure 3 controls the information identification structure to firstly identify the information code of the sample tube, store the information code into a storage unit of the equipment, and sequentially arrange the information code into the sample placement structure 16 after identification; then, the sample tubes in the sample placing structure 16 are grabbed by the tube body moving structure 21 on the operation frame 2 according to a set sequence and reach the next processing structure oscillation incubation structure 11, after entering the oscillation incubation structure 11, the liquid taking and adding structure 22 moves to the consumable material placing structure 14 according to control setting, corresponding consumable materials are installed and then move to the reagent placing structure 13, after corresponding reagents are obtained, the corresponding sample tubes are moved to the corresponding sample tube placing positions of the oscillation incubation structure 11 for reagent addition, the liquid taking and adding structure 22 leaves and moves to the discarded object placing structure 15 after the reagents are added, and the discarded consumable materials are discarded in the discarded object placing structure 15; after the reagent is added, the control structure 3 controls the oscillation incubation structure 11 to carry out oscillation or incubation treatment, and the steps of adding the reagent in the oscillation incubation treatment process are all reagent adding according to the steps; when a sample tube needs to be moved into the centrifugal structure 12, the control structure 3 controls the tube body moving structure 21 to grab the sample tube to move and place the sample tube into the centrifugal structure 12 for centrifugation, if liquid needs to be added after centrifugation, the reagent is added according to the liquid taking and adding steps, when supernatant needs to be reserved and moved into an EP tube, the EP tube is placed into the next step structure, information on the EP tube is scanned or identified through the EP tube marking and identifying structure 23 and corresponds to the corresponding sample tube information, then the liquid taking and adding structure 22 is used for moving the liquid in the sample tube into the corresponding EP tube, when the EP tube is in the oscillation incubation structure 11, oscillation incubation is carried out according to the oscillation incubation process, the reagent is added when the reagent needs to be added, and when the sample tube needs to be centrifuged again, the tube body moving structure 21 is used for moving the centrifugal structure 12; when the sediment needs to be reserved after the centrifugation is finished, the control structure 3 controls the liquid taking and adding structure 22 to draw the supernatant out of the EP pipe and discard the supernatant in the discarded object placing structure 15; after the enrichment is completed under the control of the control structure 3 according to the step of exosome enrichment, the enriched EP tube closed is placed into the enriched sample collection structure 18.
Because the entire enrichment process comprises multiple shaking incubations and centrifugation processes, each process comprises one shaking incubation and centrifugation step; dividing the reaction frame 1 of the whole device into a plurality of corresponding reaction areas according to the times of the oscillating incubation and the centrifugation process; each corresponding region is provided with an oscillation incubation structure 11, a centrifugation structure 12, a reagent placing structure 13, a consumable placing structure 14 and a waste placing structure 15. A set of operation frame 2 with a liquid taking and adding structure 22 and a tube moving structure 21 is arranged above each reaction area. Can realize the liquid of getting of flow like this and press from both sides and get the body, can not eat the problem that has the use conflict. The moving track 26 of the operation frame 2 is a track which can meet the requirement that the operation frame 2 moves to realize liquid taking and pipe body clamping. The moving rail 26 is also provided in a divided area, and is a moving rail 26 that can move in the area and can take a sample or an EP tube in the upward moving area.
To the condition that only carry out a batch sample enrichment to a process, set up a reagent and place structure 13, consumptive material and place structure 14, abandonment thing and place structure 15, set up all reagents that exosome enriched respectively in unison, the consumptive material reaches abandonment structure, can further reduce equipment occupation space, and because overall structure is less, the handling frame 2 removes and can not consume too much time.
The handling frame 2 is arranged on the setting top 24, the setting top 24 is the setting top 24 which is arranged above the reaction frame 1 and does not change relative to the position of the reaction frame 1, and the setting top 24 is provided with a moving track 26 which ensures that the handling frame 2 can move to any structure and carry out corresponding operation.
The operation frame 2 is an integral frame, on which a liquid taking and adding structure 22 and a tube body moving structure 21 are arranged, and the liquid taking and adding structure 22 and the tube body moving structure 21 can move up and down on the operation frame 2, so that one structure can play its own role.
Another embodiment of the handling frame 2 is: the two operation frames 2 are respectively a liquid taking and adding operation frame 2 and a tube body moving operation frame 2; when the operation is performed, the operation frames are respectively moved to the upper part of the corresponding structures, and when one operation frame 2 is operated, the other operation frame 2 is moved to a position where the other operation frame 2 is not interfered by the moving rail 26.
Get liquid and add liquid structure 22 and set up the operating head 25 of the same number on the body moves the structure 21, can guarantee like this to press from both sides and get the sample pipe of the same number to correspondingly carry out reagent and add.
The reagent placing structure 13 is provided with liquid taking ports corresponding to a single reagent, the number of the liquid taking ports is equal to that of the operating heads 25 of the liquid taking and adding structure 22, and the position relationship of the liquid taking ports is consistent with that of the operating heads 25; the consumable material placing structure 14 is provided with material taking ports with the number equal to that of the operating heads 25 of the liquid taking and adding structure 22 corresponding to a single consumable material;
and the position relation of the material taking port is consistent with the position relation of the operating head 25.
The number of the single-column placing holes is integral multiple of the number of the operating heads 25, or the number of the columns of the placing holes is consistent with the number of the operating heads 25, so that sample tubes can be obtained according to an effective sequence.
And a fault alarm structure 5 is arranged between each structure and the control structure 3, and when the corresponding fault alarm structure 5 sends an alarm signal, the corresponding structure is prompted to send a fault. Or, the control structure 3 is also connected with a display structure, the display structure displays the corresponding alarm structure to give an alarm, and prompts the corresponding structure to break down for maintenance, and the alarm is given in time when the complex structure is in failure.
The reaction times corresponding to the reagent amounts of any two different reagents in the reagent holding structure 13 are equal, and when the times are reached, a prompt is given or a display on the display structure is displayed for replacement. The reaction number of times that the consumptive material volume of two arbitrary different consumptive materials in the structure 14 is placed to the consumptive material corresponds also equals, and perhaps the consumptive material volume of every kind of consumptive material is the same with reagent reaction number of times, makes things convenient for whole reagent and consumptive material to change. The discard placing structure 15 is divided into a consumable discarding part 151 and a liquid discarding part 152; respectively processing the waste consumables and the liquid. The volume that abandonment thing placement structure 15 held the abandonment thing equals to hold the required space of once changing the reagent consumptive material, can change along with reagent consumptive material piece, finally can reduce the control degree of difficulty, increase efficiency.
The reagent placing structure 13, the consumable placing structure 14 and the discard placing structure 15 are arranged under the middle setting plate of the reaction frame 1, and the combination is arranged under the setting plate, so that the replacement is convenient.
The EP pipe marking and identifying structure 23 is arranged on the pipe body moving structure 21, and different identifying structures which can be in one-to-one correspondence are arranged at the top of the EP pipe; the EP tube is scanned and identified at the upper part and corresponds to the corresponding sample tube information, so that the aim of information matching is fulfilled, and the process is simple and convenient.
The enrichment sample collection structure 18 is provided with the EP tube consumable placing structure 14, or the EP tube consumable placing structure 14 is arranged in the other reaction area which is closest to the EP tube consumable placing structure 14; when the final step is reached, the EP tube is moved to the enriched sample collection structure 18 domain by the tube body moving structure 21, and then the enriched supernatant is moved to the EP tube for collection by the liquid taking and adding structure 22, and then detection is carried out.
Example 4 a process for performing blood-derived neurogenic exosomes using the apparatus of example 3 the reaction zones of example 4 were set up; the sample tube enters the sample placing structure 16 and is moved into the first reaction area by the tube body moving structure 21; performing at least one oscillation, incubation and centrifugation process, wherein the final process is a centrifugation process; adding a corresponding reagent when the reagent is required to be added; then, moving the sample tube or extracting the supernatant to the next reaction area to complete at least one oscillation, incubation and centrifugation process, wherein corresponding reagents are added in the process to carry out reaction, and the final process is a centrifugation process; when all shaking incubations and centrifugation processes are complete, the sample tube or supernatant is moved into the final enriched sample collection structure 18 for further testing.
As shown in fig. 6, the schematic of fig. 6 is only a flow diagram, and the present flow involves various exosome enrichment steps.
The above description of the embodiments is only for the understanding of the present invention. It should be noted that modifications could be made to the invention without departing from the principle of the invention, which would also fall within the scope of the claims of the invention.
Claims (9)
1. An automatic enriching apparatus for neurogenic exosomes in blood comprises a reaction frame at the bottom and a movable operation frame above the reaction frame; the control structure controls the operation frame to run according to a preset track and controls the reaction frame to react according to a set program; the device is characterized in that the reaction frame is provided with an oscillation incubation structure, a centrifugal structure, a reagent placing structure, a consumable material placing structure, a waste placing structure, a sample information identification structure and an enrichment sample collection structure after reaction, wherein the oscillation incubation structure, the centrifugal structure, the reagent placing structure, the consumable material placing structure, the waste placing structure, the sample information identification structure and the enrichment sample collection structure are required for realizing exosome enrichment; the operation frame is provided with a pipe body moving structure for moving the pipe body among different structures, and a liquid taking and adding structure for transferring liquid in the whole process is realized; in addition, an EP tube marking and identifying structure used when the EP tube is used for the first time is arranged on the reaction frame or the operation frame; the equipment also comprises a storage module capable of storing information, a control structure controls the oscillation speed and the amplitude of the oscillation incubation structure, and controls the temperature required by the corresponding step of the oscillation incubation structure; the control structure controls and monitors the reagent amount of the reagent placing structure, and prompts replacement after no reagent exists; the control structure also controls the centrifugal parameters of the centrifugal structure; the control structure monitors and records the information of the sample in the corresponding placing hole of the sample placing structure; the control structure controls the sample information to identify the sample tube information and stores the sample tube information in the storage module; the control structure controls the liquid taking and adding pipe to move to carry out the liquid taking and adding process, controls the pipe body moving structure to grab the corresponding pipe body and move to the corresponding area of the corresponding next structure, and controls the EP pipe marking and identifying structure to scan or identify the information on the EP pipe and correspond to the corresponding sample pipe information; ensuring that the patient information pair is confused or lost during the moving process; the control structure controls the last EP tube to be arranged in the enrichment sample collection structure; the handling frame sets up on setting up the top, sets up the top for the relative reaction frame position of reaction frame top does not change sets up the top, sets up the top and sets up the removal track that guarantees that the handling frame can move arbitrary structure top and carry out corresponding operation.
2. The apparatus according to claim 1, wherein only one batch of sample is enriched in one operation, and when the sample tube and the EP tube have the same structural shape, 1 oscillating incubation structure and 1 centrifugation structure are arranged in the whole process; or when the shape of the sample tube is different from that of the EP tube, the minimum number of the oscillation incubation structures and the centrifugation structures are arranged according to the requirements of the tubes with different shapes, and the whole equipment only carries out the enrichment of one batch of samples in one process.
3. The apparatus according to claim 2, wherein the operation frame is an integral frame, on which the liquid and liquid taking and adding structure and the tube moving structure are arranged, and the liquid and liquid taking and adding structure and the tube moving structure can move up and down on the operation frame, so that one structure can play its own role; or two operation frames are arranged, namely a liquid taking and filling operation frame and a pipe body moving operation frame; when the operation is performed, the operation frames move to the positions above the corresponding structures respectively, and when one operation frame acts, the other operation frame moves to the position where the other operation frame cannot be interfered through the moving track.
4. The apparatus according to claim 1, wherein a fault alarm structure is further provided between each structure and the control structure, and when the corresponding fault alarm structure sends out an alarm signal, the corresponding structure is prompted to send a fault; or the control structure is also connected with a display structure which displays the corresponding alarm structure to alarm.
5. The apparatus according to claim 1, wherein the EP tube marking and identification structure is disposed on the tube moving structure, and different identification structures capable of corresponding to each other are disposed on the top of the EP tube.
6. The apparatus according to claim 5, wherein each corresponding region is provided with an oscillation incubation structure, a centrifugation structure, a reagent placement structure, a consumable placement structure, and a waste placement structure.
7. The apparatus according to claim 5, wherein the enrichment sample collection structure is provided with an EP tube consumable placement structure.
8. The apparatus according to claim 5, wherein a set of operation frame with liquid taking and adding structure and tube moving structure is provided above each reaction region.
9. The apparatus according to claim 5, wherein the moving track is also arranged in different areas, so as to realize the moving track for moving in the local area and taking samples or EP tubes in the ascending area.
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| CN202120481103.XU CN214881524U (en) | 2021-03-05 | 2021-03-05 | Automatic enrichment apparatus for neurogenic exosomes in blood |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022184135A1 (en) * | 2021-03-05 | 2022-09-09 | 北京尔瑞鑫悦科技有限公司 | Automatic device for effective enrichment of neurogenic exosomes in blood |
| CN117625362A (en) * | 2024-01-26 | 2024-03-01 | 北京尔瑞鑫悦科技有限公司 | Blood-derived neurogenic exosome enrichment device |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022184135A1 (en) * | 2021-03-05 | 2022-09-09 | 北京尔瑞鑫悦科技有限公司 | Automatic device for effective enrichment of neurogenic exosomes in blood |
| CN117625362A (en) * | 2024-01-26 | 2024-03-01 | 北京尔瑞鑫悦科技有限公司 | Blood-derived neurogenic exosome enrichment device |
| CN117625362B (en) * | 2024-01-26 | 2024-04-16 | 北京尔瑞鑫悦科技有限公司 | Blood-derived neurogenic exosome enrichment device |
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