CN114686357A - Biological sample processing system and method - Google Patents

Biological sample processing system and method Download PDF

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Publication number
CN114686357A
CN114686357A CN202011579857.5A CN202011579857A CN114686357A CN 114686357 A CN114686357 A CN 114686357A CN 202011579857 A CN202011579857 A CN 202011579857A CN 114686357 A CN114686357 A CN 114686357A
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turntable
reagent tube
driving
driving motor
rotating
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张昊
孙振波
房瑜
魏金文
张准
乔月华
王林
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Nanjing Jinsirui Science and Technology Biology Corp
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Nanjing Jinsirui Science and Technology Biology Corp
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Priority to CN202011579857.5A priority Critical patent/CN114686357A/en
Priority to PCT/CN2021/141835 priority patent/WO2022143578A1/en
Publication of CN114686357A publication Critical patent/CN114686357A/en
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14Extraction; Separation; Purification
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/24Apparatus for enzymology or microbiology tube or bottle type
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/36Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors

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Abstract

The invention discloses a biological sample processing system, in particular to a plasmid or protein purification device. The system mainly comprises a rotary disc device with a blending function. The sample adding device, the liquid suction device and the magnetic suction device are integrated on the turntable rotating device, one or more functions of sample adding, liquid suction, uniform mixing, magnetic suction and the like can be provided, various samples can be processed at one time, the instrument is greatly simplified, and the time is saved. Compared with the existing manual operation, the operation process of experimenters is greatly simplified, and the quality of extracted products is greatly improved due to the stability of the machine. The invention also provides a biological sample processing method.

Description

Biological sample processing system and method
Technical Field
The invention belongs to the technical field of biological sample processing, and relates to a biological sample processing system and a biological sample processing method.
Background
In modern bioengineering, generally carry out the mixing reaction with multiple reagent, need carry out operations such as application of sample, transfer with reagent or sample in this process, still need to carry out magnetism to the magnetic bead when carrying out the magnetic bead processing. Mixing and other operations can not be carried out simultaneously in the existing instrument, meanwhile, the existing magnetic bead biological sample is basically processed manually by experimenters, the processing flow is complicated, the single processing quantity is small, the time consumption is long, the operation requirement on people in the operation process is high, and mistakes are easy to make.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a biological sample processing system and a biological sample processing method.
The present invention proposes a biological sample processing system, said system comprising: the rotary table rotating device and one or more of the sample adding device, the liquid suction device and the magnetic suction device are connected together through a supporting structure; wherein the content of the first and second substances,
the rotary table rotating device has a blending function and is used for rotating the reagent tube to a set station and blending the biological samples in the reagent tube; the turntable rotating device comprises a rotating turntable mechanism and a blending mechanism;
the rotary turntable mechanism mainly comprises: the device comprises a turntable, a main shaft, a bearing seat, a bearing, a supporting plate, a turntable driving device and the like; the rotary turntable mechanism is a disc-shaped structure capable of rotating around a shaft, and the rotary turntable mechanism provides power to drive the rotary turntable to rotate along the axial direction through the rotary turntable driving device.
The main shaft is connected with the turntable, penetrates through an inner hole of the bearing and is installed on the supporting plate through the bearing seat.
A first bearing and a second bearing are arranged at the upper end and the lower end of the bearing seat; the outer rings of the first bearing and the second bearing are respectively connected with the bearing seat; the main shaft penetrates through inner rings of the first bearing and the second bearing.
The turntable driving device drives the turntable to realize circumferential rotation, and the rotation angle of the turntable is judged through the position sensor.
The blending mechanism is fixed on the turntable, the number of the blending mechanisms can be set to be one or more according to the requirement, and the blending mechanisms are distributed along the circumference of the turntable to provide a plurality of rotating blending stations.
The blending mechanism mainly comprises a blending cup and a blending driving device. The blending driving device drives the blending cup to rotate along the axial direction; the axial rotation of the mixing cup and the axial rotation of the turntable are mutually independent.
When the mixing cup rotates, the biopolymer in the reagent tube arranged on the mixing cup is driven to be mixed uniformly; and/or driving the biopolymer directly added into the mixing cup to be mixed uniformly.
The turntable driving device can be a rotating motor which drives the turntable to rotate through a synchronous pulley group; the synchronous pulley group includes: a driving belt wheel, a driven belt wheel and a synchronous belt; wherein the driven pulley is fixed on the main shaft; the driven belt wheel is connected with the driving belt wheel through the synchronous belt; the driving belt wheel is fixed on a rotating motor, and the driven belt wheel is driven to rotate by the rotation of the rotating motor so as to further drive the rotary table to rotate;
the turntable driving device can directly drive the main shaft to rotate by the rotating motor; the rotating motor is directly connected with the main shaft through a coupler and drives the turntable to rotate;
the turntable driving device can be a rotary motor which drives the turntable to rotate through a gear set; the gear set includes: first driving gear, first driven gear. The rotating motor is connected with the first driving gear, and the first driven gear is connected with the main shaft; the first driving gear is meshed with the first driven gear, and the first driving gear and the first driven gear directly transmit the rotary motion of the rotary motor through tooth meshing so as to further drive the turntable to rotate.
The rotary turntable mechanism is optionally provided with a position sensor, and the function of the position sensor can be realized by a code disc and an optical coupler; the coded disc is a circular sheet and is provided with a long and thin notch, and the coded disc is fixed on the main shaft; the opto-coupler is fixed in the backup pad, whether the initial position of carousel is confirmed along with the main shaft rotation in-process to the light signal that whether shelters from the opto-coupler through the code wheel, through the rotation step number of control rotating electrical machines, the position of each mixing station on the control carousel.
The rotary turntable mechanism comprises a sliding ring; the slip ring is commercially available; the slip ring is connected with the main shaft; the main shaft is a hollow shaft; the slip ring comprises a rotor and a stator, and the rotor and the stator can still transmit electric signals in the rotating process;
a first wire harness led out by the slip ring rotor penetrates through the inner hole of the main shaft to the rotary table and is connected with a control circuit board of a first driving motor; the shell of the slip ring, namely the stator, is limited and fixed through the stop pin, and a fixed second wire harness can be led out.
The mixing cup can be directly fixed on a driving shaft of a first driving motor, the first driving motor is fixed on the lower side of the turntable, and when the first driving motor rotates, the mixing cup is driven to rotate; and/or the first driving motor is connected with the second driving gear, and the second driving gear is meshed with the second driving gear to drive the second driven gear to rotate, so that the blending cup is driven to rotate;
two second driven gears are distributed on the outer side of the second driving gear and meshed with the second driving gear; each second driven gear is provided with a mixing cup;
the blending cup and the second driven gear are fixed on the small shaft; two miniature bearings are installed at corresponding stations of the rotary table on the small shaft, penetrate through inner holes of the miniature bearings and are indirectly connected with the rotary table, and therefore the second driven gear rotates circumferentially relative to the rotary table.
The sample adding device is matched with the turntable rotating device with the blending function to add samples to the reagent tubes; the liquid suction device is matched with the rotary table rotating device with the uniformly mixing function to suck the liquid in the reagent tube; the magnetic attraction device is matched with the rotary table rotating device with the uniformly mixing function to carry out magnetic attraction operation on the magnetic beads in the reagent tube.
The sample adding device comprises: the sample adding needle fixing plate, the guide rail, the second driving motor, the first screw rod and the sample adding needle;
the sample adding device drives the sample adding needle fixing plate to move up and down under the guiding action of the guide rail through the first lead screw driven by the second driving motor when the sample is required to be added to the reagent tube, and further inserts the sample adding needle into the reagent tube to add the sample.
The pipetting device comprises: the liquid suction device comprises a third driving motor, a fourth driving motor, a liquid suction needle, a liquid suction arm and a second screw rod;
the liquid suction needle is fixed on a liquid suction arm of the liquid suction device, and the liquid suction device drives the second screw rod to drive the liquid suction arm to rotate through the third driving motor; the liquid suction device drives the second screw rod to drive the liquid suction arm to axially and vertically move up and down through the fourth driving motor; when the reagent tube needs to suck liquid, the third driving motor rotates the liquid sucking needle to the position above the reagent tube, the fourth driving motor drives the liquid sucking needle to move towards the inside of the reagent tube, and when the liquid sucking needle moves to a set position, liquid in the reagent tube is sucked out.
The device is inhaled to magnetism includes: the magnetic attraction device comprises a synchronous belt, a fifth driving motor, a magnet assembly, a main synchronous wheel and a slave synchronous wheel;
the fifth driving motor is directly connected with the main synchronizing wheel, and the main synchronizing wheel drives the slave synchronizing wheel to rotate through the synchronous belt of the magnetic attraction device, so that the magnet assembly is driven to move, the magnet assembly is close to or far away from the reagent tube, and the biological sample is magnetically attracted.
The invention also provides a biological sample processing method, which adopts the processing system and specifically comprises the following steps:
step 1: respectively inserting a plurality of reagent tubes filled with biological samples into the mixing cup;
step 2: the turntable rotating device rotates the reagent tube to a set sample adding position, and the sample adding device adds the reagent into the reagent tube;
and step 3: starting a motor of the turntable rotating device, rotating the reagent tube forward and backward, and fully and uniformly mixing the biological sample in the reagent tube;
and 4, step 4: the uniformly mixed biological sample reaches a set magnetic attraction position through the rotation of the turntable, and the magnetic attraction device adsorbs magnetic beads in the reagent tube;
and 5: after the adsorption is finished, the liquid absorption device absorbs the waste liquid in the reagent tube;
step 6: by rotation of the carousel, a plurality of biological samples may be processed in succession.
The beneficial effects of the invention include: the biological sample processing system can add one or more functions of sample adding, absorbing, magnetic attraction and the like on the basis of sample mixing, can process various samples at one time, greatly simplifies the instrument and saves time. Compared with the existing manual operation, the operation process of experimenters is greatly simplified, and the quality of extracted products is greatly improved due to the stability of the machine.
Drawings
FIG. 1 is a schematic view of the entire structure of a turntable rotating apparatus according to the present invention.
Fig. 2 is a first perspective view of the overall structure of the turntable rotating device according to the present invention.
Fig. 3 is a second perspective view of the overall structure of the turntable rotating device according to the present invention.
Fig. 4 is a schematic view of the turntable directly driven by the rotating motor of the turntable rotating device according to the present invention.
Fig. 5 is a schematic view of the rotary motor of the turntable rotating device of the present invention driving the turntable to rotate through the gear set.
Fig. 6 is a sectional view showing the rotation of the main shaft of the turntable rotating device in the present invention.
Fig. 7 is a schematic view of a slip ring leading out a wire harness of the turntable rotating apparatus of the present invention.
FIG. 8 is a schematic view of the mixing mode of the mixing cup driven by the gear of the turntable rotating device.
FIG. 9 is a schematic structural view of a kneading cup in a kneading mode driven by a gear of a turntable rotating device according to the present invention relative to a turntable.
FIG. 10 is a schematic view of the mixing mode of the mixing cup directly driven by the motor of the turntable rotating device.
FIG. 11 is a schematic top view of the principal apparatus of the treatment system of the present invention.
FIG. 12 is a schematic diagram of the overall configuration of the processing system of the present invention.
FIG. 13 is a schematic view of the structure of the sample adding device of the present invention.
FIG. 14 is a schematic view of the wicking apparatus of the present invention.
FIG. 15 is a schematic view of the magnetic attraction device of the present invention.
FIGS. 16a and 16b are schematic views of two methods of using the magnetic attraction device of the present invention.
In FIGS. 1-16:
100-rotary turntable mechanism, 110-turntable, 161-rotary motor, 121-code disc, 122-optical coupler, 162-synchronous belt, 163-driving pulley, 164-driven pulley, 153-stop pin, 165-coupler, 130-main shaft, 167-first driven gear, 166-first driving gear, 140-bearing seat, 141-first bearing, 142-second bearing, 150-slip ring, 151-first wiring harness, 152-second wiring harness and 160-turntable driving device;
200-a blending mechanism, 212-a blending cup, 214-a second driven gear, 213-a second driving gear, 211-a first driving motor, 215-a small shaft, 216-a first micro bearing, 217-a second micro bearing, 218-a shaft sleeve and 210-a blending driving device;
220-a reagent tube;
300-a support plate;
400-a control circuit board;
500-turntable rotation means;
600-a sample adding device, 601-a sample adding needle fixing plate, 602-a guide rail, 603-a second driving motor, 604-a first screw rod and 605-a sample adding needle;
700-a liquid suction device, 701-a third driving motor, 702-a fourth driving motor, 703-a liquid suction needle, 704-a liquid suction arm and 705-a second screw rod;
800-magnetic attraction device, 801-fifth driving motor, 802-magnetic attraction device synchronous belt, 803-magnet assembly, 804-main synchronous wheel and 805-slave synchronous wheel;
900-a support structure;
1000-cleaning device.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples and the accompanying drawings. The procedures, conditions, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
The invention discloses a biological sample processing device, in particular to a plasmid or protein purification device. The system mainly comprises a rotary disc device with a blending function. The sample adding device, the liquid suction device and the magnetic suction device are integrated on the turntable rotating device, and one or more functions of sample adding, liquid suction, uniform mixing, magnetic suction and the like can be provided.
The biological sample processing system in the present embodiment includes: a turntable rotating device 500 with a blending function, a sample adding device 600, a liquid absorbing device 700 and a magnetic absorbing device 800 which are connected together through a supporting structure 900. In practice, the biological sample processing system of the present invention can also integrate any one or any combination of the sample adding device 600, the pipetting device 700, and the magnetic device 800 on only the carousel rotating device.
The turntable rotating device 500 in this embodiment is used for rotating the reagent tube 220 to a set station and uniformly mixing the biological samples in the reagent tube 220; the structure is shown in fig. 1-10, and comprises two mechanisms: a rotating turntable mechanism 100 and a blending mechanism 200.
The rotary disk mechanism 100 in the present embodiment includes: the turntable 110, the main shaft 130, the bearing seat 140, the first bearing 141, the second bearing 142, the turntable driving device 160, and the support plate 300.
The rotary turntable mechanism 100 is a disc-shaped structure capable of rotating around a shaft, 16 stations are distributed along the circumference of the outer side of a disc in a circle, 16 samples can be stored, and the samples can be rotated to preset positions according to process requirements; the rotary turntable mechanism 100 is powered by the turntable driving device 160 to drive the turntable 110 to rotate in the axial direction.
The bearing seat 140 is fixed on the upper side of the support plate 300, the upper end and the lower end of the bearing seat 140 are respectively provided with a first bearing 141 and a second bearing 142, and the outer rings of the first bearing 141 and the second bearing 142 are respectively connected with the bearing seat 140;
the main shaft 130 passes through the inner rings of the first bearing 141 and the second bearing 142, the upper side of the main shaft 130 is connected with the turntable 110, and the lower side of the main shaft 130 is connected with the turntable driving device 160; and thus the turntable 110 has only one degree of freedom of pivoting with respect to the support plate 300.
The turntable driving device 160 may be a rotating motor 161 connected to the main shaft 130 through a synchronous pulley set to drive the turntable 110 to rotate; synchronous pulley set includes: a driving pulley 163, a driven pulley 164, and a timing belt 162 having a reduction ratio of 1:6 for reducing the rotation speed of the turntable 110 and amplifying the output torque of the rotating motor 161 by 6 times.
The driven pulley 164 is directly fixed on the main shaft 130 and connected with the driving pulley 163 through the synchronous belt 162; the driving pulley 163 is directly fixed on the rotating motor 161, and the rotation of the rotating motor 161 drives the driven pulley 164 to rotate, so as to further drive the turntable 110 to rotate;
the turntable driving device 160 may be a rotating motor 161 connected to the main shaft 130 through a gear set to drive the turntable 110 to rotate; the gear set includes: the first driving gear 166, the first driven gear 167, the reduction ratio of the gear set is 1: 6; the first driving gear 166 is fixed on the rotating motor 161, and drives the main shaft 130 to rotate by meshing with the first driven gear 167, and further drives the turntable 110 to rotate;
the turntable driving device 160 may also be a rotary motor 161 directly connected to the spindle 130 through a coupling 165 to drive the turntable 110 to rotate.
A coded disc 121 with a long and thin gap is fixed on the lower side of the main shaft 130, an optocoupler 122 is fixed on a corresponding position of the support plate 300, when the long and thin gap rotates to the center of the optocoupler 122, a receiving end of the optocoupler receives a signal sent by a transmitting end of the optocoupler, and the position is the initial position of the turntable 110; the rotary motor 161 drives the turntable 110 to rotate by a fixed angle, and further drives the blending cup 212 to reach a set position.
A slip ring 150 is fixed on the main shaft 130, and the slip ring 150 is commercially available; the main shaft 130 is a hollow shaft; a first wiring harness 151 led out from the rotor of the slip ring 150 penetrates through the inner hole of the main shaft 130 to the turntable 110, is connected with a control circuit board 400 of the first driving motor 211 and rotates together with the turntable 110; the stator, which is the housing of the slip ring 150, is fixed in position by the stopper pin 153, and the second harness 152 led out is fixed, so that the winding phenomenon does not occur after the harness in the turntable 110 is led out to the outside.
In this embodiment, the 16 blending mechanisms 200 are uniformly distributed on the circumference of the outer ring of the rotating disc 110. When the samples need to be mixed uniformly, the corresponding mixing mechanism 200 rotates to drive the samples to be mixed uniformly;
the mixing mode comprises two types: one is that the first driving motor 211 directly drives the blending cup 212 to rotate; the other is that the first driving motor 211 drives the blending cup 212 to rotate through the meshing transmission of the second driving gear 213 and the second driven gear 214.
The first driving motor 211 directly drives the blending cup 212 to blend, that is, the blending cup 212 is directly fixed on the driving shaft of the first driving motor 211 through screws; the first driving motor 211 is fixed at the lower side of the turntable 110, and when the first driving motor 211 rotates, the first driving motor drives the blending cup 212 to rotate; the reagent tube 220 can also be installed on the blending cup 212, when the first driving motor 211 rotates, the reagent tube 220 is driven to rotate and blend, in this embodiment, the highest blending speed does not exceed 1400r/min, and forward and reverse rotation can be realized.
The first driving motor 211 can also drive the two mixing cups 212 to rotate by the engagement of the second driving gear 213 and the two second driven gears 214; the first driving motor 211 is fixed at the lower side of the turntable 110 and connected with the second driving gear 213 through the turntable 110; two second driven gears 214 are distributed on the outer side of the second driving gear 213 to be meshed with the second driving gear, and each of the two second driven gears 214 corresponds to one station and is connected with the blending cup 212 to respectively drive the blending cup 212 to rotate.
The 16 second driven gears 214 are uniformly distributed at the outer sides of the 8 second driving gears 213 along the circumference of the turntable 110; 8 second driving gears 213 are controlled by 8 first driving motors 211 respectively, the rotation of the second driving gears 213 drives two second driven gears 214 to rotate, and the second driven gears 214 and the second driving gears 213 have 1: 2, so that the rotating speed of the blending cup 211 is amplified, and better blending is realized, in the embodiment, the highest blending speed is not more than 1400r/min, and two second driven gears 214 controlled by the same first driving motor 211 have the same rotating speed and reverse rotating directions;
the blending cup 212 and the second driven gear 214 are directly fixed on the small shaft 215 and positioned at the upper side of the rotating disc 110; two miniature bearings 216 and 217 are arranged at 16 stations of the turntable 110, a small shaft 215 passes through inner holes of the first miniature bearing 216 and the second miniature bearing 217 at each station and is connected with a second driven gear 214, and a shaft sleeve 218 is arranged between the second driven gear 214 and the first miniature bearing 216; the second driven gear 214 can rotate relative to the turntable 110 to drive the biopolymer in the blending cup 212 to blend.
When the sample adding device 600 in this embodiment is used, the sample adding needle 605 can move up and down in the Z direction, and can rotate around the Z axis, and the sample adding device 600 is matched with the turntable rotating device 500 with the blending function to add samples to the reagent tube 220; the structure includes: a sample adding needle fixing plate 601, a guide rail 602, a second driving motor 603, a first screw rod 604 and a sample adding needle 605;
specifically, the sample adding device 600 of the present invention cooperates with the turntable rotating device 500 to add samples to the reagent tube 220, the sample adding needle fixing plate 601 is provided with at least one sample adding needle 605, when the reagent tube 220 needs to add samples, the turntable rotating device 500 rotates the reagent tube 220 to be added with samples to the lower side of the sample adding needle 605 through the rotating motor 161, the sample adding device 600 drives the first lead screw 604 through the second driving motor 603, the sample adding needle fixing plate 601 is driven to move up and down under the guiding action of the guide rail 602, and the sample adding needle 605 is further inserted into the reagent tube 220 to add samples. Further, a plurality of sample addition needles 605 are attached to the sample addition needle fixing plate 601, and different liquids can be added to the reagent tubes 220 by sucking a predetermined amount of reagents from the prepared reagent bottles. In practice, the sample adding device 600 can also be in a synchronous belt form, or can be realized through a gantry mechanism, and other structures capable of realizing the sample adding function.
The liquid absorbing device 700 in this embodiment is matched with the turntable rotating device 500 with the blending function to absorb the liquid in the reagent tube 220; the structure includes: a third driving motor 701, a fourth driving motor 702, a liquid suction needle 703, a liquid suction arm 704 and a second screw rod 705;
the liquid suction needle 703 is fixed on the liquid suction device 700, the liquid suction device 700 can also provide two degrees of freedom of movement, namely, the third driving motor 701 drives the second screw rod 705 to drive the liquid suction arm 704 to rotate through driving the second screw rod 705, and the fourth driving motor 702 drives the liquid suction arm 704 to axially and vertically move up and down through driving the second screw rod 705; when the reagent tube 220 needs to suck liquid, the turntable rotating device 500 rotates the reagent tube 220, which needs to discharge waste liquid, to a predetermined position through the rotating motor 161, the third driving motor 701 rotates the liquid suction needle 703 to the upper side of the reagent tube 220, the fourth driving motor 702 drives the liquid suction needle 703 to move into the reagent tube 220, and when the liquid suction needle 703 moves to a set position, liquid in the reagent tube 220 is sucked out under the action of the external pump body. After the waste liquid suction operation is completed, the pipette device 700 removes the pipette needle 703 from the reagent tube 220, and sends the pipette needle 703 to an external washing tank for washing. After the cleaning is completed, the pipette device 700 removes the pipette needle 703 from the cleaning tank, and performs waste liquid suction treatment of the other reagent tubes 220, thereby preventing cross infection. In practice, the pipetting operation of the liquid in the reagent tube can be realized by driving the pipetting needle to pipette from other positions in the belt rotating and lifting mode and by other motion mechanisms, including but not limited to the modes of a mechanical arm, a portal frame and the like.
The structure of the magnetic attraction device 800 in this embodiment includes: a magnetic attraction device synchronous belt 802, a fifth driving motor 801, a magnet assembly 803, a main synchronous wheel 804 and a slave synchronous wheel 805; the magnetic attraction device 800 can realize the radial movement of the magnet, the magnetic attraction device 800 is matched with the turntable rotating device 500 with the uniform mixing function, the magnet assembly 803 is arranged at the outer side of the reagent tube 220 needing magnetic attraction, and the magnetic attraction operation is carried out on the magnetic beads in the reagent tube 220;
specifically, when the magnetic beads in the reagent tube 220 need to be magnetically attracted, the turntable rotating device 500 rotates the reagent tube 220 to be magnetically attracted to the position directly opposite to the magnetic attraction device 800 through the rotating motor 161, the fifth driving motor 801 is directly connected to the main synchronizing wheel 804, the main synchronizing wheel 804 drives the slave synchronizing wheel 805 to rotate through the synchronous belt 802 of the magnetic attraction device, so as to drive the magnet assembly 803 to move back and forth to be close to or away from the reagent tube 220, and when the magnet assembly 803 is close to the outer wall of the reagent tube 220, the magnetic beads in the sample are sucked out from the reagent tube 220, as shown in fig. 16 a; alternatively, the magnet assembly 803 is extended into the reagent tube from the position right above the reagent tube 220 by internal magnetic attraction, so as to suck the magnetic beads in the sample out of the reagent tube 220, as shown in fig. 16 b. Further, after the magnetic beads are magnetically absorbed out of the reagent tube 220, the liquid absorption device 700 drives the liquid absorption needle 703 to absorb the waste liquid in the reagent tube 220.
In this embodiment, a cleaning device 1000 is further included for cleaning the outer wall of the pipette 703. Specifically, the cleaning device 1000 includes a cleaning tank, a first diaphragm pump, and a second diaphragm pump; wherein, the pipette needle 703 moves into the cleaning tank, the side wall of the cleaning tank is provided with at least one small hole, which is connected with the first diaphragm pump through a pipeline and is used for spraying cleaning liquid to clean the pipette needle 703; the second diaphragm pump is used for pumping the generated washing liquid away from the washing pool. In practice, if the pipetting device is in the form of a TIP head, the cleaning device 1000 may not be provided. The cleaning device 1000 may be implemented using other structures that achieve the same function.
The biological sample processing method in the present embodiment includes the steps of:
step 1: respectively inserting a plurality of reagent tubes filled with biological samples into the mixing cup;
step 2: the turntable rotating device rotates the reagent tube to a set sample adding position, and the sample adding device adds the reagent into the reagent tube;
and step 3: starting a motor of the turntable rotating device, rotating the reagent tube forward and backward, and fully and uniformly mixing the biological sample in the reagent tube;
and 4, step 4: the uniformly mixed biological sample reaches a set magnetic attraction position through the rotation of the turntable, and the magnetic attraction device adsorbs magnetic beads in the reagent tube;
and 5: after the adsorption is finished, the liquid absorption device absorbs the waste liquid in the reagent tube;
step 6: by rotation of the carousel, a plurality of biological samples may be processed in succession.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, which is set forth in the following claims.

Claims (8)

1. A biological sample processing system, the system comprising: one or more of a turntable rotating device (500), a sample adding device (600), a liquid absorbing device (700) and a magnetic absorbing device (800) which are connected together through a supporting structure (900); wherein the content of the first and second substances,
the turntable rotating device (500) includes: a rotary disc mechanism (100) and a blending mechanism (200); the rotary turntable mechanism (100) is a disc-shaped structure capable of rotating around a shaft, and the rotary turntable (110) is driven to rotate along the axial direction by the power provided by the turntable driving device (160); the blending mechanism (200) comprises: a blending driving device (210) and a blending cup (212); one or more blending mechanisms (200) are fixed on the turntable (110); the blending driving device (210) drives the blending cup (212) to rotate along the axial direction; the axial rotation of the blending cup (212) and the axial rotation of the rotating disc (110) are mutually independent;
the sample adding device (600) is matched with the turntable rotating device (500) to add samples to the reagent tubes (220);
the liquid suction device (700) is matched with the rotary disc rotating device (500) to suck liquid in the reagent tube (220);
the magnetic attraction device (800) is matched with the turntable rotating device (500) to carry out magnetic attraction operation on magnetic beads in the reagent tube (220).
2. The biological sample processing system of claim 1, wherein the sample application device (600) comprises: the device comprises a sampling needle fixing plate (601), a guide rail (602), a second driving motor (603), a first screw rod (604) and a sampling needle (605);
the sample adding device comprises a sample adding needle fixing plate (601), wherein at least one sample adding needle (605) is arranged on the sample adding needle fixing plate (601), samples are added to a reagent tube (220), when the reagent tube (220) needs to add samples, the sample adding device (600) drives a first screw rod (604) through a second driving motor (603), the sample adding needle fixing plate (601) is driven to move up and down under the guiding effect of a guide rail (602), and the sample adding needle (605) further penetrates into the reagent tube (220) to add samples.
3. The biological sample processing system of claim 1, wherein the pipetting device (700) comprises: a third driving motor (701), a fourth driving motor (702), a liquid suction needle (703), a liquid suction arm (704) and a second screw rod (705);
the liquid suction needle (703) is fixed on the liquid suction device (700), and the liquid suction device (700) drives the second screw rod (705) to drive the liquid suction arm (704) to rotate through the third driving motor (701); the liquid suction device (700) drives a second screw rod (705) to drive a liquid suction arm (704) to axially and vertically move up and down through the fourth driving motor (702); when the reagent tube (220) needs to suck liquid, the third driving motor (701) drives the second screw rod (705) to drive the liquid sucking arm (704) to rotate the liquid sucking needle (703) to the upper side of the reagent tube (220), the fourth driving motor (702) drives the second screw rod (705) to drive the liquid sucking arm (704) to drive the liquid sucking needle (703) to move towards the inside of the reagent tube (220), and when the liquid sucking needle (703) moves to a set position, liquid in the reagent tube (220) is sucked out.
4. The biological sample processing system of claim 1, wherein the magnetically attractive device (800) comprises: a magnetic attraction device synchronous belt (802), a fifth driving motor (801), a magnet assembly (803), a main synchronous wheel (804) and a slave synchronous wheel (805);
wherein, fifth driving motor (801) and main synchronizing wheel (804) direct link to each other, main synchronizing wheel (804) are through device hold-in range (802) are inhaled to magnetism drives from synchronizing wheel (805) and rotates to drive magnet subassembly (803) motion, be close to or keep away from reagent pipe (220), magnetism is inhaled to the magnetic bead in the biological sample.
5. The biological sample processing system of claim 1, wherein the rotary carousel mechanism (100) comprises: the rotary table comprises a rotary table (110), a main shaft (130), a bearing seat (140), bearings (141, 142), a rotary table driving device (160) and a supporting plate (300);
the main shaft (130) is connected with the turntable (110), and the main shaft (130) penetrates through inner holes of the bearings (141, 142) and is installed on the support plate (300) through a bearing seat (140);
the turntable driving device (160) further comprises: a rotating electric machine (161) and a transmission mechanism;
the transmission mechanism includes: a synchronous belt (162), synchronous pulleys (163 and 164), or a coupling (165), or gear sets (166 and 167);
the rotating motor (161) is directly connected with the main shaft (130) through a coupler (165) and drives the turntable (110) to rotate; or is connected with the main shaft (130) through synchronous pulleys (163, 164) and a synchronous belt (162) to drive the turntable (110) to rotate; or is connected with the main shaft (130) through gear sets (166, 167) to drive the turntable (110) to rotate.
6. The biological sample processing system of claim 1, wherein the mixing cup (212) is directly fixed to a drive shaft of the first drive motor (211) to rotate the mixing cup (212); and/or the first driving motor (211) is connected with the second driving gear (213), and the second driving gear (213) is meshed to drive the second driven gear (214) to rotate so as to drive the blending cup (212) to rotate;
the first driving motor (211) is fixed on the circumference of the turntable (110);
a second driven gear (214) is distributed outside the second driving gear (213) and meshed with the second driving gear;
when the mixing cup (212) rotates, the biopolymer in the reagent tube (220) arranged on the mixing cup (212) is driven to be mixed uniformly; and/or the mixing cup (212) is driven to directly add the biopolymer into the mixing cup (212) to mix uniformly when rotating.
7. The biological specimen processing system of claim 6, wherein the mixing cup (212) and the second driven gear (214) are secured to a small shaft (215);
two miniature bearings (216, 217) are installed on the small shaft (215) at corresponding stations of the rotary table (110), and the small shaft (215) penetrates through inner holes of the miniature bearings (216, 217) to be indirectly connected with the rotary table (110), so that the driven gear (214) can rotate circularly relative to the rotary table (110).
8. A method for processing biological samples, using a processing system according to any one of claims 1 to 7, the method comprising the steps of:
step 1: respectively inserting a plurality of reagent tubes (220) filled with biological samples into the mixing cup;
and 2, step: the turntable rotating device (500) rotates the reagent tube (220) to a set sample adding position, and the sample adding device (600) adds the reagent into the reagent tube (220);
and step 3: starting a motor of the turntable rotating device, rotating the reagent tube (220) forward and backward, and fully and uniformly mixing the biological sample in the reagent tube (220);
and 4, step 4: the uniformly mixed biological sample reaches a set magnetic attraction position through the rotation of the turntable (110), and the magnetic attraction device (800) adsorbs magnetic beads in the reagent tube (220);
and 5: after the adsorption is finished, the liquid absorption device (700) absorbs the waste liquid in the reagent tube (220);
step 6: by rotation of the turntable (110), a plurality of biological samples can be processed in succession.
CN202011579857.5A 2020-12-28 2020-12-28 Biological sample processing system and method Pending CN114686357A (en)

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CN115304003B (en) * 2022-08-23 2023-10-27 楚天科技股份有限公司 Magnetic microbead coating machine
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