CN116086710B - Single-cell library preparation equipment, sealing detection method and control device thereof - Google Patents
Single-cell library preparation equipment, sealing detection method and control device thereof Download PDFInfo
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Abstract
The invention discloses single-cell library preparation equipment and a sealing detection method and a control device thereof, wherein the single-cell library preparation equipment comprises a chip, a sealing gasket, a gas circuit board, a pressing motor, a detector and a control device, the chip is provided with a liquid containing groove with an upward notch, the sealing gasket is covered on the notch and is provided with air holes in a penetrating way, the gas circuit board is arranged on the upper side of the sealing gasket and can press the sealing gasket downwards in a movable way, the gas circuit board is provided with gas circuits which correspond to the air holes and can be filled towards the liquid containing groove, the pressing motor is arranged on the upper side of the chip and is used for driving the gas circuit board to move up and down, the detector is used for detecting the operation parameters of the pressing motor, the control device is electrically connected with the detector and the pressing motor, and the sealing detection method of the single-cell library preparation equipment comprises the following steps: acquiring an actual operation parameter variation value of a pressing motor; and comparing the actual operation parameter change value with a preset threshold value, and judging the sealing state of the liquid containing tank. The invention aims to solve the problems that the existing flow channel lacks detection air tightness and single cell library preparation is affected.
Description
Technical Field
The invention relates to the technical field of single-cell library preparation, in particular to single-cell library preparation equipment, a sealing detection method and a control device thereof.
Background
The existing single-cell library preparation system is generally provided with a warehouse-in and warehouse-out structure to send the microfluidic chip into the inner cavity of the shell, so as to complete the preparation process. In general, air pressure is adopted to promote cell liquid to flow in a flow channel of a microfluidic chip so as to smoothly finish preparation, so that the flow channel maintains good air tightness, and is important for preparing a single cell library.
Disclosure of Invention
The invention mainly aims to provide single-cell library preparation equipment, a sealing detection method and a sealing detection control device thereof, and aims to solve the problem that the existing flow channel lacks detection air tightness and influences the preparation of single-cell libraries.
In order to achieve the above object, the present invention provides a seal detection method for a single-cell library preparation apparatus, where the single-cell library preparation apparatus includes a chip, a seal gasket, a gas circuit board, a pressing motor, a detector, and a control device, the chip has a liquid tank with an upward notch, the seal gasket is covered on the notch of the liquid tank and is provided with a gas hole extending vertically, the gas circuit board is disposed on an upper side of the seal gasket and can move downward to press the seal gasket, the gas circuit board has a gas circuit corresponding to the gas hole, the gas circuit can be inflated toward the liquid tank, the pressing motor is disposed on the upper side of the chip and is used for driving the gas circuit board to move up and down, the detector is used for detecting an operation parameter of the pressing motor, and the control device is electrically connected with the detector and the pressing motor, and the seal detection method for the single-cell library preparation apparatus includes the following steps:
acquiring an actual operation parameter change value of the downward-pressing motor;
and comparing the actual operation parameter change value with a preset threshold value, and judging the sealing state of the liquid containing tank.
Optionally, the step of obtaining the actual operation parameter variation value of the pressing motor includes:
acquiring an initial operation parameter change value of the downward-pressing motor;
and when the initial operation parameter change value is larger than a preset change value, taking the initial operation parameter change value as the actual operation parameter change value.
Optionally, in the step of judging the sealing state of the liquid container according to the comparison between the actual operation parameter variation value and a preset threshold value,
and when the actual operation parameter change value is in the range of a preset threshold value, judging that the liquid containing tank is in a sealing state.
Optionally, when the actual operation parameter variation value is within a range of a preset threshold, the step of determining that the liquid container is in a sealed state includes:
calculating to obtain an actual running parameter average value in the rated time when the gas circuit board is in an inflated state;
after the rated time is met, the current actual operation parameter value is obtained;
calculating to obtain the ratio of the actual running parameter average value to the actual running parameter value;
and if the ratio meets the preset condition, judging that the liquid containing tank is in a sealing state.
Optionally, the ratio of the average value of the actual running parameter to the actual running parameter value is a, and the preset condition is 1.4-1.6.
Optionally, in the step of judging the sealing state of the liquid container according to the comparison between the actual operation parameter variation value and a preset threshold value,
when the actual operation parameter change value exceeds the preset threshold value, judging that the liquid containing tank is abnormally sealed, and generating an abnormal control instruction;
and according to the abnormal control instruction, controlling the air circuit board to stop inflating and controlling the air circuit board to move upwards until the air circuit board is spaced from the chip.
Optionally, the actual operating parameter variation value includes at least one of an operating current variation value and an operating power variation value.
The invention also provides a control device, which comprises a memory, a processor and a control program of single-cell library preparation equipment, wherein the control program of the single-cell library preparation equipment is stored on the memory and can run on the processor, and is configured to realize the steps of the sealing detection method of the single-cell library preparation equipment.
The invention also provides single cell library preparation equipment, which comprises the following steps:
the chip is provided with a liquid containing groove on the notch;
the sealing gasket is covered on the notch of the liquid containing groove and is provided with an air hole extending vertically;
the air passage plate is arranged on the upper side of the sealing gasket and can move downwards to press the sealing gasket, and is provided with an air passage corresponding to the air hole, and the air passage can be inflated towards the liquid containing groove;
the pressing motor is arranged on the upper side of the chip and used for driving the air circuit board to move up and down; the method comprises the steps of,
the detector is used for detecting the operation parameters of the pressing motor;
control means, as described above, electrically connected to the detector and the piezoelectrics.
Optionally, the number of the chips is multiple, each chip is provided with a plurality of liquid containing tanks, and the liquid containing tanks are arranged at intervals along the length direction of the chip;
the air holes are arranged in a plurality corresponding to the chips, and the air holes are distributed in a matrix.
According to the technical scheme, the chip is provided with the liquid containing groove with the upward notch, the sealing pad is arranged on the upper side of the chip and is used for covering the notch of the containing groove, the air channel plate is arranged on the upper side of the sealing pad and can press the sealing pad downwards in a movable mode, so that the sealing pad seals the containing groove, the sealing pad is provided with air holes, the air holes are communicated with the containing groove and the air channels of the air channel plate, and therefore air can be filled into the containing groove through the air holes through the air channels of the air channel plate to drive cell liquid in the containing cavity to flow; the detector is used for detecting the operation parameters of the pressing motor, and the sealing state of the liquid containing tank is judged according to the change value of the operation parameters, so that an operator can conveniently detect the sealing state of the sealing gasket and the chip, the preparation of a single-cell library is ensured to be carried out smoothly, and the efficiency is improved.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to the structures shown in these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic perspective view of an apparatus for preparing a single cell library according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a control device of a hardware operating environment according to the present invention;
FIG. 3 is a schematic flow chart of a seal detection method of single cell library preparation equipment provided by the invention;
FIG. 4 is a flow chart of a seal detection method of single cell library preparation equipment provided by the invention.
Reference numerals illustrate:
the achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that, if directional indications (such as up, down, left, right, front, and rear … …) are included in the embodiments of the present invention, the directional indications are merely used to explain the relative positional relationship, movement conditions, etc. between the components in a specific posture (as shown in the drawings), and if the specific posture is changed, the directional indications are correspondingly changed.
In addition, if there is a description of "first", "second", etc. in the embodiments of the present invention, the description of "first", "second", etc. is for descriptive purposes only and is not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In addition, the meaning of "and/or" as it appears throughout includes three parallel schemes, for example "A and/or B", including the A scheme, or the B scheme, or the scheme where A and B are satisfied simultaneously. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the combination of the technical solutions should be considered to be absent and not within the scope of protection claimed in the present invention.
The existing single-cell library preparation system is generally provided with a warehouse-in and warehouse-out structure to send the microfluidic chip into the inner cavity of the shell, so as to complete the preparation process. In general, air pressure is adopted to promote cell liquid to flow in a flow channel of a microfluidic chip so as to smoothly finish preparation, so that the flow channel maintains good air tightness, and is important for preparing a single cell library.
In view of the above, the present invention provides a single-cell library preparing apparatus, a seal detecting method and a control device thereof, wherein the seal degree between a chip and a sealing pad can be monitored by monitoring an operation parameter of a pressing motor, fig. 1 and fig. 2 are a flow chart of an embodiment of the single-cell library preparing apparatus provided by the present invention, and fig. 3 and fig. 4 are a flow chart of an embodiment of the seal detecting method of the single-cell library preparing apparatus provided by the present invention.
Referring to fig. 1, the single-cell library preparing apparatus 100 includes a chip 1, a sealing pad 2, a gas circuit board 3, a pressing motor, a detector, and a control device, wherein the chip 1 has a liquid container on a notch; the sealing gasket 2 is covered on the notch of the liquid containing groove, and the sealing gasket 2 is provided with air holes extending vertically; the air passage plate 3 is arranged on the upper side of the sealing gasket 2 and can move downwards to press the sealing gasket 2, the air passage plate 3 is provided with an air passage corresponding to the air hole, and the air passage can be inflated towards the liquid containing groove; the lower piezoelectric motor is arranged on the upper side of the chip 1 and is used for driving the air circuit board 3 to move up and down; the detector is used for detecting the operation parameters of the pressing motor; the control device is electrically connected with the detector and the lower piezoelectric motor.
In this embodiment, the chip 1 is formed with a liquid container with an upward notch, the sealing pad 2 is disposed on the upper side of the chip 1 and is used for covering the notch of the liquid container, the air channel plate 3 is disposed on the upper side of the sealing pad 2, and can press the sealing pad 2 in a downward moving manner, so that the sealing pad 2 seals the liquid container, the sealing pad 2 is provided with air holes, the air holes are communicated with the liquid container and the air channels of the air channel plate 3, so that the air holes can be inflated toward the liquid container through the air channels of the air channel plate 3 to drive the cell liquid in the liquid container to flow; the detector is used for detecting the operation parameters of the pressing motor, and the sealing state of the liquid containing groove is judged according to the change value of the operation parameters, so that an operator can conveniently detect the sealing state of the sealing gasket 2 and the chip 1, the preparation of a single-cell library is ensured to be carried out smoothly, and the efficiency is improved.
The detector includes at least one of a current sensor, a power sensor, and a pressure sensor.
Further, in this embodiment, a plurality of chips 1 are provided, and each chip 1 is provided with a plurality of liquid tanks, and the liquid tanks are arranged at intervals along the length direction of the chip 1; the number of the air holes is plural corresponding to the plurality of chips 1, and the plurality of air holes are distributed in a matrix. Thus, a plurality of chips 1 can be prepared together, and the preparation efficiency is improved.
Referring to fig. 2, fig. 2 is a schematic structural diagram of a control device of a hardware running environment according to an embodiment of the present invention. As shown in fig. 2, the control device may include: a processor 1001, such as a central processing unit (Central Processing Unit, CPU), a communication bus 1002, a user interface 1003, a network interface 1004, a memory 1005. Wherein the communication bus 1002 is used to enable connected communication between these components. The user interface 1003 may include a Display, an input unit such as a Keyboard (Keyboard), and the optional user interface 1003 may further include a standard wired interface, a wireless interface. The network interface 1004 may optionally include a standard wired interface, a Wireless interface (e.g., a Wireless-Fidelity (Wi-Fi) interface). The Memory 1005 may be a high-speed random access Memory (Random Access Memory, RAM) or a stable nonvolatile Memory (NVM), such as a disk Memory. The memory 1005 may also optionally be a storage device separate from the processor 1001 described above.
It will be appreciated by those skilled in the art that the configuration shown in fig. 2 is not limiting of the control device and may include more or fewer components than shown, or may be combined with certain components, or may be arranged in a different arrangement of components.
As shown in fig. 2, an operating system, a network communication module, a user interface module, and a single cell library preparation apparatus 100 control program may be included in a memory 1005 as one storage medium.
In the control device shown in fig. 2, the network interface 1004 is mainly used for data communication with a network server; the user interface 1003 is mainly used for data interaction with a user; the processor 1001 and the memory 1005 in the control device of the present invention may be provided in the control device, and the control device calls the control program of the single-cell library preparation apparatus 100 stored in the memory 1005 through the processor 1001, and executes the seal detection method of the single-cell library preparation apparatus provided in the embodiment of the present invention.
Referring to fig. 3 and 4, the sealing detection method of the single cell library preparation apparatus 100 specifically includes the following steps:
s10, acquiring an actual operation parameter change value of the downward-pressing motor;
specifically, the actual operation parameter variation value includes a current variation value or a power variation value of the down-pressing motor, or a current variation value and a power variation value.
S20, comparing the actual operation parameter change value with a preset threshold value, and judging the sealing state of the liquid containing tank.
According to the technical scheme, a liquid containing groove with an upward notch is formed in the chip 1, the sealing pad 2 is arranged on the upper side of the chip 1 and is used for covering the notch of the liquid containing groove, the air channel plate 3 is arranged on the upper side of the sealing pad 2 and can press the sealing pad 2 downwards in a movable mode, so that the sealing pad 2 seals the liquid containing groove, the sealing pad 2 is provided with air holes, the air holes are communicated with the liquid containing groove and the air channels of the air channel plate 3, and therefore air can be filled into the liquid containing groove through the air holes through the air channels of the air channel plate 3 to drive cell liquid containing liquid in the liquid containing cavity to flow; the detector is used for detecting the operation parameters of the pressing motor, and the sealing state of the liquid containing groove is judged according to the change value of the operation parameters, so that an operator can conveniently detect the sealing state of the sealing gasket 2 and the chip 1, the preparation of a single-cell library is ensured to be carried out smoothly, and the efficiency is improved.
Specifically, the step S10 further includes the steps of:
s11, acquiring an initial operation parameter change value of the downward-pressing motor;
and S12, when the initial operation parameter change value is larger than a preset change value, taking the initial operation parameter change value as the actual operation parameter change value.
The single cell library preparation apparatus 100 includes a mounting base for detachably mounting the chip 1; when the single cell library preparation apparatus 100 does not mount the chip 1, the sealing gasket 2 is pressed onto the mounting seat, and the mounting seat itself does not form a closed cavity, so that the initial operation parameter variation value is very small and smaller than the preset variation value, thereby being capable of judging that the chip 1 is not mounted in the mounting seat, and distinguishing the situation that the single cell library preparation apparatus 100 does not mount the chip 1, so as to remind an operator of mounting the chip 1 and avoid damaging the single cell library preparation apparatus 100.
When the initial operation parameter variation value is greater than a preset variation value, the chip 1 is mounted in the mounting seat, so that the step 20 includes the steps of:
s21, when the actual operation parameter change value is in the range of a preset threshold value, judging that the liquid containing tank is in a sealing state.
It can be known that, if the liquid containing cavity is in a sealed state, after the air passage of the air passage plate 3 begins to be inflated, the pressure in the liquid containing cavity may be increased, in order to maintain sealing, the air passage plate 3 needs to maintain to compress the sealing gasket 2, and due to force interaction, the pressure of the air passage plate 3 to the sealing gasket 2 needs to be increased, so that the power of the pressing motor needs to be increased, so that the operation parameter of the pressing motor may change to a certain extent, and the liquid containing groove is determined to be in a sealed state when the actual operation parameter change value is within a range of a preset threshold value, and at this time, the sealing state of the chip 1 is good.
In addition, the step S20 further includes:
s22, when the actual operation parameter change value exceeds the preset threshold value, judging that the liquid containing tank is abnormally sealed, and generating an abnormal control instruction;
s23, according to the abnormal control instruction, controlling the air circuit board 3 to stop inflating, and controlling the air circuit board 3 to move upwards until the air circuit board is spaced from the chip 1.
In this embodiment, when the sealing gasket 2 is biased, misalignment between the air path of the air path board 3 and the air hole of the sealing gasket 2 occurs, so that the air path of the air path board 3 directly corresponds to the surface of the sealing gasket 2, and the pressure of the sealing gasket 2 is larger and is larger than the pressure of the chip 1 in a sealing state, that is, exceeds the preset threshold; therefore, when the actual operation parameter variation value exceeds the preset threshold value, the abnormal sealing of the liquid containing tank can be judged, meanwhile, the single-cell library preparation equipment 100 can also produce an abnormal control instruction, the gas circuit board 3 is controlled to stop inflating according to the abnormal control instruction, the gas circuit board 3 is controlled to move upwards to be spaced apart from the chip 1, and an operator can conveniently align the sealing gasket 2, so that the safety performance is improved.
Specifically, the step S21 further includes:
s211, calculating to obtain an actual running parameter average value in rated time when the air circuit board 3 is in an inflated state;
s212, after the rated time is met, acquiring the current actual operation parameter value;
s213, calculating to obtain the ratio of the actual running parameter average value to the actual running parameter value;
s214, if the ratio meets the preset condition, judging that the liquid containing tank is in a sealing state.
In this embodiment, the gas circuit board 3 is in an inflated state, and calculates an actual running parameter average value in a rated time, and after the rated time is satisfied, a current actual running parameter value is obtained, because when the gas circuit of the gas circuit board 3 is inflated, the pressure in the liquid containing cavity will rise steeply with time, and when the steep rise is too large, it may also represent that the sealing gasket 2 is abnormal, so the ratio of the actual running parameter average value to the actual running parameter value needs to be within a preset condition, specifically, the ratio is a, the preset condition is 1.4.ltoreq.a.ltoreq.1.6, and the sealing effect when a=1.5 is optimal.
In the present invention, when the pressure of the air circuit board 3 is greater, the power of the pressing motor is greater, so that the current of the pressing motor is also greater.
The foregoing description is only of the preferred embodiments of the present invention and is not intended to limit the scope of the invention, and all equivalent structural changes made by the description of the present invention and the accompanying drawings or direct/indirect application in other related technical fields are included in the scope of the invention.
Claims (7)
1. The utility model provides a sealing detection method of single cell library preparation equipment, its characterized in that, single cell library preparation equipment includes chip, sealed pad, gas circuit board, pushes down motor, detector and controlling means, the chip has notch ascending appearance cistern, sealed pad lid is located the notch setting of appearance cistern to through being equipped with along the gas pocket that extends down, the gas circuit board is located sealed upper side of pad, can move down in order to suppress sealed pad, the gas circuit board has the gas circuit that corresponds the gas pocket, the gas circuit can be aerifyd towards appearance cistern, lower piezoelectric motor locates the upper side of chip is used for driving the gas circuit board reciprocates, the detector is used for detecting the operating parameter of pushing down motor, controlling means with detector with lower piezoelectric motor electricity is connected, single cell library preparation equipment's sealing detection method includes the following steps:
acquiring an actual operation parameter change value of the downward-pressing motor;
comparing the actual operation parameter variation value with a preset threshold value, and judging the sealing state of the liquid containing tank;
the step of obtaining the actual running parameter variation value of the pressing motor comprises the following steps:
acquiring an initial operation parameter change value of the downward-pressing motor;
when the initial operation parameter change value is larger than a preset change value, the initial operation parameter change value is used as the actual operation parameter change value;
the step of judging the sealing state of the liquid containing tank according to the comparison of the actual operation parameter variation value and a preset threshold value comprises the following steps:
when the actual operation parameter change value is in the range of a preset threshold value, judging that the liquid containing tank is in a sealing state;
when the actual operation parameter change value exceeds the preset threshold value, judging that the liquid containing tank is abnormally sealed, and generating an abnormal control instruction;
and according to the abnormal control instruction, controlling the air circuit board to stop inflating and controlling the air circuit board to move upwards until the air circuit board is spaced from the chip.
2. The method for detecting the sealing of a single cell library preparation apparatus according to claim 1, wherein the step of determining that the liquid container is in a sealed state when the actual operation parameter variation value is within a preset threshold value comprises:
calculating to obtain an actual running parameter average value in the rated time when the gas circuit board is in an inflated state;
after the rated time is met, the current actual operation parameter value is obtained;
calculating to obtain the ratio of the actual running parameter average value to the actual running parameter value;
and if the ratio meets the preset condition, judging that the liquid containing tank is in a sealing state.
3. The method for detecting the sealing of single-cell library preparation equipment according to claim 2, wherein the ratio of the average value of the actual operation parameters to the actual operation parameter value is a, and the preset condition is 1.4.ltoreq.a.ltoreq.1.6.
4. The method for detecting the sealing of a single-cell library preparation apparatus according to claim 1, wherein the actual operation parameter variation value comprises at least one of an operation current variation value and an operation power variation value.
5. A control device, characterized in that the control device comprises a memory, a processor and a control program of a single-cell library preparation apparatus stored on the memory and executable on the processor, the control program of the single-cell library preparation apparatus being configured to implement the steps of the seal detection method of the single-cell library preparation apparatus according to any one of claims 1 to 4.
6. A single cell library preparation apparatus, comprising:
the chip is provided with a liquid containing groove on the notch;
the sealing gasket is covered on the notch of the liquid containing groove and is provided with an air hole extending vertically;
the air passage plate is arranged on the upper side of the sealing gasket and can move downwards to press the sealing gasket, and is provided with an air passage corresponding to the air hole, and the air passage can be inflated towards the liquid containing groove;
the pressing motor is arranged on the upper side of the chip and used for driving the air circuit board to move up and down; the method comprises the steps of,
the detector is used for detecting the operation parameters of the pressing motor;
a control device as claimed in claim 5, said control device being electrically connected to said detector and said piezoresistor.
7. The single cell library preparation apparatus of claim 6, wherein a plurality of said chips are provided, each of said chips having a plurality of said liquid holding tanks, said plurality of said liquid holding tanks being disposed at intervals along the length of said chip;
the air holes are arranged in a plurality corresponding to the chips, and the air holes are distributed in a matrix.
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| US4811252A (en) * | 1986-04-04 | 1989-03-07 | Kabushiki Kaisha Kosumo Keiki | Leakage test equipment |
| KR20140123243A (en) * | 2013-04-12 | 2014-10-22 | 주식회사 나노엔텍 | chip for single cell electrophoretic measurement, holding unit for the same and device for single cell electrophoretic measurement |
| CN107983423B (en) * | 2017-10-19 | 2020-08-07 | 广州市第一人民医院 | Device for preparing micro-droplets quickly at high flux and application thereof |
| JP2021525550A (en) * | 2018-06-01 | 2021-09-27 | エス２ ゲノミクス インコーポレイテッド | Methods and equipment for processing tissue samples |
| CN113737286B (en) * | 2021-08-24 | 2022-09-30 | 北京寻因生物科技有限公司 | Single cell library preparation system, control method thereof and storage medium |
| CN114958573A (en) * | 2021-12-31 | 2022-08-30 | 墨卓生物科技(浙江)有限公司 | Transmission device and single cell sequencer comprising same |
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| CN114958574A (en) * | 2021-12-31 | 2022-08-30 | 墨卓生物科技(浙江)有限公司 | Processing equipment for single cell sequencing |
Non-Patent Citations (1)
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| 《基于气泵的连续反应体系中多试剂驱动系统的研究》;莫丹;《中国优秀硕士学位论文全文数据库 (工程科技Ⅱ辑)》;C029-270 * |
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