Jack method, device and equipment of multi-channel nanopore sensor and storage medium

Abstract

The embodiment of the invention discloses a jack inserting method, device and equipment for a multi-channel nanopore sensor and a storage medium. The method comprises the following steps: respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into a nanopore or not; and when it is detected that the preset channel is inserted into the nanopore, controlling the corresponding multiplexing switch to switch the preset channel to the target channel. According to the technical scheme provided by the embodiment of the invention, the next channel is not required to be switched to jack after the preset channel in all groups of channels completes jack insertion, so that the jack insertion time can be greatly saved, and the jack insertion efficiency is improved. And the phenomenon that multiple holes are inserted into the same channel can be effectively avoided, and the yield can be improved.

Description

Technical Field

[0001] The embodiments of the present invention relate to the field of gene sequencing technology, and in particular to a method, device, equipment and storage medium for inserting a multi-channel nanopore sensor. Background Art

[0002] With the rapid development of gene sequencing technology, the third-generation sequencing technology represented by single-molecule nanopore sequencing technology has attracted widespread attention due to its advantages such as ultra-long read length, real-time detection, direct reading of modified bases, and direct reading of RNA.

[0003] Nanopore sensors utilize nanopore arrays containing hundreds or even thousands of nanopores for analyte detection. However, not all nanopores remain functional after production or during the detection process. To improve data acquisition efficiency, reduce costs, and conserve space, signal acquisition systems often group multiple nanopores together and select the best-quality nanopore for detection. This involves switching circuits between multiple pore channels to select the optimal channel for analyte detection.

[0004] In the related art, there are problems of long time consumption and low yield in the insertion process of multi-channel nanopore sensors. Summary of the Invention

[0005] The embodiments of the present invention provide a method, device, equipment and storage medium for inserting a multi-channel nanopore sensor to solve the problems of long insertion time and low yield in the related art.

[0006] According to one aspect of the present invention, a method for inserting a multi-channel nanopore sensor is provided, wherein each group of channels of the multi-channel nanopore sensor to be inserted is connected to a multiplexing switch, and the method for inserting a multi-channel nanopore sensor comprises:

[0007] respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore;

[0008] When it is detected that the preset channel is inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the preset channel to the target channel.

[0009] Optionally, the separately detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore comprises:

[0010] detecting the current values ​​in the preset channels in the same group of channels once every first preset time;

[0011] It is determined whether the preset channel is inserted into the nanopore according to the current value; if the current value is greater than or equal to a current threshold, it is determined that the preset channel is inserted into the nanopore.

[0012] Optionally, the insertion method of the multi-channel nanopore sensor further comprises:

[0013] If the preset channel is not detected to be inserted into the nanopore for a second preset time, controlling the corresponding multiplexing switch to switch the preset channel to the target channel;

[0014] Wherein, the second preset time is greater than the first preset time;

[0015] The insertion method of the multi-channel nanopore sensor further includes:

[0016] When the preset channel is switched to the last channel in the same group of channels and the jack detection is completed, the multiplexing switch is controlled to be turned off.

[0017] Optionally, each channel group of the multi-channel nanopore sensor includes four channels, and the insertion method of the multi-channel nanopore sensor includes:

[0018] detecting whether a first channel in each group of channels of the multi-channel nanopore sensor is inserted into a nanopore at every first preset time;

[0019] If the first channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the first channel to the second channel; if the first channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the first channel to the second channel;

[0020] detecting whether the second channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time;

[0021] If the second channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the second channel to the third channel; if the second channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the second channel to the third channel;

[0022] detecting whether the third channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time;

[0023] If the third channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the third channel to the fourth channel; if the third channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the third channel to the fourth channel;

[0024] detecting whether the fourth channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time;

[0025] If the fourth channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to be turned off; if the fourth channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to be turned off.

[0026] Optionally, the insertion method of the multi-channel nanopore sensor further comprises:

[0027] Whenever it is detected that the preset channel is inserted into the nanopore, the insertion ratio of the multi-channel nanopore sensor is counted.

[0028] Optionally, after the third preset time of starting the insertion, whenever the preset channel is detected to be inserted into the nanopore, the insertion ratio of the multi-channel nanopore sensor is counted once.

[0029] Optionally, the insertion method of the multi-channel nanopore sensor further comprises:

[0030] When all channels in the channel group are switched to the last channel, if the insertion ratio is less than the preset ratio, the channel in the same channel group that is not inserted with the nanopore is used as the preset channel, and cyclic detection is performed, and channel switching is performed between the channels that are not inserted with the nanopore;

[0031] Until the insertion ratio of the multi-channel nanopore sensor is greater than or equal to the preset ratio, the multiplexing switches corresponding to each group of channels are controlled to be turned off.

[0032] Optionally, before respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore, the method further comprises:

[0033] adding a nanopore protein solution to the multi-channel nanopore sensor;

[0034] The multiplexing switch is controlled to switch each group of channels to the preset channel, and a fixed voltage is applied to the preset channel.

[0035] Optionally, when the insertion is completed, the nanopore protein solution in the multi-channel nanopore sensor is replaced.

[0036] According to another aspect of the present invention, there is provided a jack device for a multi-channel nanopore sensor, comprising:

[0037] a detection unit, configured to respectively detect whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore;

[0038] The switch switching unit is used to control the corresponding multiplexing switch to switch the preset channel to the target channel when detecting that the preset channel is inserted into the nanopore.

[0039] According to another aspect of the present invention, an electronic device is provided, comprising:

[0040] one or more processors;

[0041] a storage device for storing one or more programs;

[0042] When the one or more programs are executed by the one or more processors, the one or more processors are enabled to implement the insertion method of the multi-channel nanopore sensor provided by any embodiment of the present invention.

[0043] According to another aspect of the present invention, a computer-readable storage medium is provided, on which a computer program is stored. When the program is executed by a processor, the insertion method of the multi-channel nanopore sensor provided by any embodiment of the present invention is implemented.

[0044] The technical solution provided by the embodiments of the present invention detects whether a preset channel in each channel group of a multi-channel nanopore sensor has been inserted into a nanopore. Upon detecting a preset channel being inserted into a nanopore, the corresponding multiplexing switch is controlled to immediately switch the preset channel to the target channel, eliminating the need to wait for all preset channels in the channel group to complete insertion before switching to the next channel for insertion. This significantly reduces insertion time and improves insertion efficiency. Furthermore, because channel switching is performed immediately upon detecting a channel being inserted into a nanopore, the transmembrane voltage of the already inserted channel is not affected, reducing the probability of inserting a nanopore into the same channel again and effectively avoiding the phenomenon of multiple nanopores being inserted into the same channel, which helps improve product yield.

[0045] It should be understood that the content described in this section is not intended to identify the key or important features of the embodiments of the present invention, nor is it intended to limit the scope of the present invention. Other features of the present invention will become readily understood through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0047] Figure 1 A schematic structural diagram of a jack system of a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0048] Figure 2 A flow chart of a method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0049] Figure 3 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0050] Figure 4 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0051] Figure 5 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0052] Figure 6 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0053] Figure 7 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0054] Figure 8 A flow chart of another method for inserting a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0055] Figure 9 A schematic structural diagram of a jack device for a multi-channel nanopore sensor provided by an embodiment of the present invention;

[0056] Figure 10 A schematic structural diagram of an electronic device provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0057] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0058] It should be noted that the terms "first", "second", etc. in the description and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that the numbers used in this way can be interchanged where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0059] The jacking method of the multi-channel nanopore sensor provided by an embodiment of the present invention can be applicable to nanopore sequencing scenarios, wherein the jacking method can be performed by an electronic device, which can be implemented in the form of software and / or hardware, and the electronic device can include a multi-channel nanopore sensor system. Figure 1 A schematic structural diagram of a multi-channel nanopore sensor system according to an embodiment of the present invention, referring to Figure 1 The multi-channel nanopore sensor's jack system includes a multiplexing switch 12, a power supply module 13, a signal detection module 14, and a control module 15. The multi-channel nanopore sensor 11 to be inserted is connected between the first end of the power supply module 13 and the first end of the multiplexing switch 12. The second end of the power supply module 13 is connected to the second end of the multiplexing switch 12 via the signal detection module 14 and the control module 15. The control module 15 is connected to the control end of the multiplexing switch 12. The control module 15 is used to control the switching of the multiplexing switch 12, enabling the multi-channel nanopore sensor to switch multiple channels. The power supply module 13 can be used to provide a DC voltage, and the signal detection module 14 can be used to detect the jack signal to determine whether a nanopore is inserted into a channel. For example, the signal detection module 14 can communicate bidirectionally with the control module 15. The control module 15 transmits the received jack signal to the signal detection module 14. After signal processing, the signal detection module 14 feeds back a switching signal to the control module 15. The control module 15 controls the multiplexing switch 12 to switch channels based on the switching signal.

[0060] The multi-channel nanopore sensor 11 includes a plurality of nanopore unit arrays, each of which includes a plurality of nanopore units 110. Each nanopore unit array is connected to a multiplexer switch 12. The multiplexer switch 12 is controlled by the control module 15 to connect each nanopore unit 110 one by one to realize the switching of multiple channels. The nanopore unit 110 can be formed on a substrate 105, which can be a silicon-based substrate. The nanopore unit 110 includes a chamber 106 formed by a first dielectric layer 104 and a second dielectric layer 102, and the chamber 106 contains an electrolyte. A membrane 101 is provided above the chamber 106 (away from the side of the substrate 105). The membrane 101 can be a biological membrane or a non-biological membrane.

[0061] A working electrode 103 is also disposed between the substrate 105 and the nanopore unit 110. An electrolyte, such as a nanopore protein solution, is also disposed between the working electrode 103 and the nanopore unit 110. By applying a voltage to the working electrode 103 and the counter electrode 120, the nanopore protein is inserted into the membrane 101 through an electroporation process induced by the voltage signal, thereby forming a nanopore in the membrane 101. The multiple membranes in the nanopore unit array can be unconnected, and each nanopore unit 110 can be an independent structure. In actual use, DNA sequence information can be obtained by analyzing the different current changes caused by DNA molecules passing through the nanopores.

[0062] Figure 2 A flowchart of a multi-channel nanopore sensor insertion method provided by an embodiment of the present invention, referring to Figure 2 The method for inserting a multi-channel nanopore sensor provided in this embodiment includes:

[0063] S110 , detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore.

[0064] Specifically, as analyzed above, the process of inserting a pore into membrane 101 typically requires applying a transmembrane voltage across membrane 101. Under the influence of this voltage, the nanopore protein inserts into membrane 101, thereby forming a nanopore. For nanopore sensors 11 with multi-channel circuit systems, a multiplexer switch 12 is typically used to switch channels. During operation, only one switch of the multiplexer switch 12 is in operation. To ensure that each channel in each channel group of nanopore sensor 11 is inserted into the nanopore under the influence of the voltage, the multiplexer switch 12 must be continuously switched to ensure that each channel in each channel group of the nanopore sensor is connected in a time-sharing manner.

[0065] Here, the channels of the nanopore sensor can be nanopore units 110. Each nanopore unit 110 corresponds to a channel, and each channel corresponds to a switch. When a switch of the multiplexing switch 12 is turned on, a transmembrane voltage is applied across the nanopore unit 110 connected to that switch. The preset channel can be any channel in a group of channels. For example, the first channel in each group of channels is used as the preset channel. That is, each multiplexing switch 12 selects the switch corresponding to the first channel to turn on, and detects whether a nanopore is inserted into the first channel in each group of channels. Multiple groups of channels can be detected simultaneously.

[0066] S120 , when it is detected that the preset channel is inserted into the nanopore, controlling the corresponding multiplexing switch to switch the preset channel to the target channel.

[0067] The multiplex switches 12 corresponding to the various channels of the multi-channel nanopore sensor are independently controlled and do not restrict each other.

[0068] Specifically, when a preset channel in a channel group or several channels detects that a nanopore has been inserted, the multiplexing switch 12 corresponding to the channel with the inserted nanopore is controlled to switch to switch the preset channel in the corresponding channel group to the target channel. The target channel is a channel different from the preset channel. For example, if the preset channel is the first channel, the next uninserted channel after the target channel can be the second channel or the third channel. In other words, as soon as the preset channel in a channel group is detected to have a nanopore inserted, the preset channel in the channel group is immediately switched to the next channel, without having to wait for all preset channels in the channel group to complete insertion before switching to the next channel for insertion.

[0069] The technical solution provided by the embodiments of the present invention detects whether a preset channel in each channel group of a multi-channel nanopore sensor has been inserted into a nanopore. Upon detecting a preset channel being inserted into a nanopore, the corresponding multiplexing switch is controlled to immediately switch the preset channel to the target channel, eliminating the need to wait for all preset channels in the channel group to complete insertion before switching to the next channel for insertion. This significantly reduces insertion time and improves insertion efficiency. Furthermore, because channel switching is performed immediately upon detecting a channel being inserted into a nanopore, the transmembrane voltage of the already inserted channel is not affected, reducing the probability of inserting a nanopore into the same channel again and effectively avoiding the phenomenon of multiple nanopores being inserted into the same channel, which helps improve product yield.

[0070] Optionally, in this embodiment, after applying a transmembrane voltage to both ends of the membrane 101 of the nanopore unit 110 , it is possible to determine whether a nanopore is inserted into the membrane 101 of the channel by detecting the current in the channel.

[0071] Figure 3 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 3 Based on the above embodiment, optionally, the insertion method of the multi-channel nanopore sensor provided in this embodiment includes:

[0072] S1101 , detecting current values ​​in preset channels in the same channel group once every first preset time.

[0073] S1102 , determining whether the preset channel is inserted into the nanopore according to the current value; if the current value is greater than or equal to the current threshold, determining that the preset channel is inserted into the nanopore.

[0074] Specifically, when a transmembrane voltage is applied to both ends of the membrane 101, no current flows through the channel of the membrane 101 without a pore. When a nanopore is inserted into the membrane 101, the nanopore changes the state of the membrane 101, allowing current to flow through the channel. Typically, the current value after the channel is inserted is between 100pA and 200pA, and the current threshold can be a fixed value greater than 0 and less than or equal to 100pA. Optionally, by setting the current threshold to close to 100pA (lower current limit), it is helpful to ensure the accuracy of the detection.

[0075] Because insertion requires a process, the current value in each of the multiple channels is measured at a first preset time interval. When the detected current value is greater than or equal to a current threshold, it is determined that a nanopore is inserted into the channel. If the detected current value is less than the current threshold, it is determined that no nanopore is inserted into the channel. The first preset time can be set based on actual detection conditions; for example, the first preset time can be 5 seconds.

[0076] S120 , when it is detected that the preset channel is inserted into the nanopore, controlling the corresponding multiplexing switch to switch the preset channel to the target channel.

[0077] Figure 4 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 4 Based on the above embodiment, optionally, the insertion method of the multi-channel nanopore sensor provided in this embodiment includes:

[0078] S1101 , detecting current values ​​in preset channels in the same channel group once every first preset time.

[0079] S1102 , determining whether the preset channel is inserted into the nanopore according to the current value; if the current value is greater than or equal to the current threshold, determining that the preset channel is inserted into the nanopore.

[0080] S120 , when it is detected that the preset channel is inserted into the nanopore, controlling the corresponding multiplexing switch to switch the preset channel to the target channel.

[0081] S130 : If the insertion of the preset channel into the nanopore is not detected for a second preset time, controlling the corresponding multiplexing switch to switch the preset channel to the target channel.

[0082] Specifically, when no nanopore is detected inserted into the preset channel every first preset time, the current value of the preset channel continues to be detected. If no nanopore is detected inserted into the preset channel after the second preset time (that is, there is no obvious change in the current value in the preset channel), the multiplexer switch 12 corresponding to the channel group of the preset channel is also controlled to switch to the target channel, so as to prevent the preset channel without a nanopore being detected for an unlimited time, so as to improve the overall insertion efficiency of the multi-channel nanopore sensor.

[0083] Optionally, in this embodiment, the second preset time is greater than the first preset time. For example, the second preset time may be 20 seconds. For the same group of channels, the preset channel is checked every 5 seconds to see if a nanopore is inserted. If no nanopore is detected in the preset channel by the 20th second, the preset channel is no longer checked, and the corresponding multiplexing switch is controlled to immediately switch to the target channel, and the target channel is checked every 5 seconds to see if a nanopore is inserted. The above process is repeated until the last channel is switched.

[0084] In an optional implementation provided by this embodiment, when the preset channel is switched to the last channel in the same group of channels and the jack detection is completed, the corresponding multiplexing switch 12 is controlled to be turned off until all the multiplexing switches 12 are turned off to complete the jack process.

[0085] Figure 5 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 1 and Figure 5 Taking a channel group comprising four nanopore units 110 as an example, i.e., a channel group comprising four channels, the multi-channel nanopore sensor comprises hundreds or thousands of matrices each comprising four channels, with hundreds or thousands of multiplexing switches 12 controlling the switching of each channel group. Taking a first preset time of 5 seconds and a second preset time of 20 seconds as an example, the insertion method of the multi-channel nanopore sensor specifically includes:

[0086] First, each multiplexing switch 12 is switched to the first channel. The first channel in each channel group is connected to the power supply module 13 through the corresponding multiplexing switch 12. Every 5 seconds, the first channel in each channel group of the multi-channel nanopore sensor is checked to see if it is inserted into the nanopore. If the first channel is detected to be inserted into the nanopore, the corresponding multiplexing switch 12 is controlled to switch the first channel to the second channel. If the first channel is not detected to be inserted into the nanopore for 20 seconds, the corresponding multiplexing switch 12 is controlled to switch the first channel to the second channel.

[0087] When switching to the second channel, the sensor checks every 5 seconds to see if a nanopore is inserted into the second channel of each channel group. If an insertion into the nanopore is detected, the corresponding multiplexing switch 12 is controlled to switch the second channel to the third channel. If no insertion into the nanopore is detected for 20 seconds, the corresponding multiplexing switch 12 is controlled to switch the second channel to the third channel.

[0088] When switching to the third channel, the sensor checks every 5 seconds to see if the third channel in each channel group is inserted into the nanopore. If the third channel is detected to be inserted into the nanopore, the corresponding multiplexing switch 12 is controlled to switch the third channel to the fourth channel. If the third channel is not detected to be inserted into the nanopore for 20 seconds, the corresponding multiplexing switch 12 is also controlled to switch the third channel to the fourth channel.

[0089] When switching to the fourth channel, each channel group in the multi-channel nanopore sensor is tested every 5 seconds to see if the fourth channel is inserted into the nanopore. If the fourth channel is detected as inserted into the nanopore, the corresponding multiplexing switch 12 is controlled to be turned off. If the fourth channel is not detected as inserted into the nanopore for 20 seconds, the corresponding multiplexing switch 12 is also controlled to be turned off. When all groups of channels have switched to the fourth channel, the insertion test is completed and the insertion can be terminated.

[0090] Alternatively, Table 1 shows the test results obtained using a related technique for detecting all groups of preset channels and inserting a certain proportion of nanopores, followed by switching to the target channel. Table 2 shows the test results obtained using the technique provided in this embodiment. Both test schemes employed the same transmembrane voltage and the same environment.

[0091] Table 1

[0092]

[0093] Table 2

[0094]

[0095] Among them, each channel is inserted with only one nanopore as a valid jack, and the others are invalid jacks, that is, each nanopore unit 110 is inserted with only one nanopore on the membrane 101 as a valid jack. Referring to Table 1 and Table 2, in ten groups of test results, compared with the relevant technical solutions, the use of the technical solution provided in this embodiment for jacking can reduce the average jacking time from 38min to 9.6min, greatly reducing the jacking time and improving the jacking efficiency. The porosity is reduced from 27.2% to 11.1%, and the non-porous rate is reduced from 10.8% to 9.7%, greatly improving the yield of the product. Therefore, through the technical solution provided in this embodiment, the nanopore protein can be efficiently inserted into the membrane 101 of the multi-channel nanopore sensor in a short time, and it is not easy to insert into the pores, and the product has a high yield.

[0096] Optionally, during the insertion process, each time a predetermined channel is detected to be inserted into the nanopore, the insertion ratio of the multi-channel nanopore sensor can be counted to observe the current insertion status in real time. Here, the insertion ratio counted each time refers to the current insertion ratio.

[0097] As a preferred implementation provided by this embodiment, after a third preset time has passed since the start of insertion, the insertion ratio of the multi-channel nanopore sensor can be calculated each time a predetermined channel is detected to have been inserted into a nanopore. For example, before insertion begins, the multi-channel nanopore sensor has a nanopore on its channel to be inserted, i.e., the insertion ratio at this time is 0. As insertion begins, the insertion ratio gradually increases over time. Upon reaching the third preset time, the insertion ratio of the multi-channel nanopore sensor can be calculated each time a predetermined channel is detected to have been inserted into a nanopore. The third preset time can be determined by the total insertion time; for example, if the total insertion time is 10 minutes, the insertion ratio can be measured starting at the 5th minute. The third preset time can also be determined by the insertion ratio; for example, if the insertion process lasts for 9 minutes and a 70% insertion ratio is achieved, the insertion ratio can be measured starting at the 4th minute. The technical solution provided by this embodiment uses a method of measuring the insertion ratio while inserting a hole to enable real-time monitoring of the current insertion status, while also improving detection efficiency.

[0098] In another optional implementation provided by this embodiment, when all channels in each channel group are switched to the last channel by the multiplexing switch 12, if the insertion ratio does not meet the requirement, a second round of insertion can be enabled until the insertion ratio meets the requirement. The insertion ratio here refers to the ratio of effective holes.

[0099] Figure 6 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 6The method for inserting a multi-channel nanopore sensor provided in this embodiment includes:

[0100] S110 , detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore.

[0101] S120 , when it is detected that the preset channel is inserted into the nanopore, controlling the corresponding multiplexing switch to switch the preset channel to the target channel.

[0102] S210, when all channels in the channel group are switched to the last channel, if the jack ratio is less than the preset ratio, the channel in the same channel group that is not inserted with the nanopore is used as the preset channel, and cyclic detection is performed, and channel switching is performed between the channels that are not inserted with the nanopore;

[0103] S211 , until the insertion ratio of the multi-channel nanopore sensor is greater than or equal to a preset ratio, controlling the multiplexing switches corresponding to each group of channels to be turned off.

[0104] Specifically, Figure 7 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 7 The process before switching to the fourth channel in the same channel group can be referred to Figure 5 The relevant description in will not be repeated here. When switching to the fourth channel, the fourth channel in each group of channels of the multi-channel nanopore sensor is detected every 5 seconds to see if the nanopore is inserted. If it is detected that the fourth channel is inserted into the nanopore, and it is detected that the current insertion ratio is less than the preset ratio, the second round of insertion is started, that is, the channel that was not inserted into the nanopore during the first round of insertion is used as the preset channel to continue the second round of insertion. If the fourth channel is still not detected to be inserted into the nanopore for 20 seconds, the second round of insertion is also started. For example, after the first round of insertion, if the insertion rate of the multi-channel nanopore sensor does not meet the requirements, the second round of insertion is continued. If in the same group of channels, the second channel and the fourth channel are not inserted into the nanopore during the first round of insertion, the second channel is used as the preset channel in the group of channels, and the multiplexing switch 12 is controlled to switch to the second channel. Every 5 seconds, it is detected whether the second channel in the group of channels is inserted into the nanopore. If a nanopore is detected in the second channel, the corresponding multiplexing switch 12 is controlled to switch from the second channel to the fourth channel. If no nanopore is detected in the second channel for 20 seconds, the corresponding multiplexing switch 12 is similarly controlled to switch the second channel to the fourth channel. This step is repeated multiple times until the nanopore insertion rate of the multi-channel nanopore sensor is greater than or equal to a preset ratio. At this point, each multiplexing switch 12 is controlled to shut off, ending the insertion process. The preset ratio can be 80%. In actual applications, the preset insertion ratio can be flexibly adjusted according to actual sequencing requirements.

[0105] It should be understood that among hundreds or thousands of channel groups, not all channels in each group have a nanopore inserted during the first round of insertion. It is possible that the first channel in some channel groups has a nanopore inserted, and / or the second channel in some channel groups has a nanopore inserted, and / or the third channel in some channel groups has a nanopore inserted, and / or the fourth channel in some channel groups has a nanopore inserted. It is also possible that at least one channel in some channel groups has a nanopore inserted, while all channels in other channel groups have a nanopore inserted. Therefore, during the second round of insertion, in the same channel group, the channels without nanopores inserted are used as the preset channels, and the channels with nanopores inserted are skipped, and only switching is performed between the channels without nanopores. The preset channels in different channel groups may be different, and the target channels to be switched to may also be different. If the insertion rate after the second round of insertion is still less than the preset ratio, a third and fourth round of insertion can be performed until the insertion rate is greater than or equal to the preset ratio.

[0106] The technical solution provided in this embodiment can start multiple rounds of jack insertion processes to ensure the jack insertion quality while reducing the jack insertion time and improving the jack insertion efficiency.

[0107] Optionally, in each of the above embodiments, the multiplexing switch 12 may be turned off manually by an operator or automatically. For example, the multiplexing switch 12 may be automatically turned off by controlling the control module 15 .

[0108] Figure 8 A flowchart of another method for inserting a multi-channel nanopore sensor according to an embodiment of the present invention is provided. Figure 8 On the basis of the above technical solutions, optionally, before step S110, the multi-channel nanopore sensor insertion method further includes:

[0109] S310, adding the nanopore protein solution to the multi-channel nanopore sensor.

[0110] S320 , controlling the multiplexing switch to switch each group of channels to a preset channel, and applying a fixed voltage to the preset channel.

[0111] Specifically, after the multi-channel nanopore sensor to be inserted is connected to the multi-channel nanopore sensor insertion system, a nanopore protein solution is added to the multi-channel nanopore sensor. Subsequently, a multiplexing switch is controlled to switch each channel group to a preset channel, so that the two ends of the membrane 101 corresponding to the preset channel are connected to the multi-channel nanopore sensor insertion system. A transmembrane voltage is applied to the two ends of the membrane 101 via the power supply module 13. The nanopore protein solution is a protein with nanopores that can be inserted into the membrane 101 under the action of a voltage, thereby forming a nanopore in the membrane 101.

[0112] Optionally, when the insertion is completed, the nanopore protein solution in the multi-channel nanopore sensor is replaced so that the DNA molecules can be sequenced in the subsequent sequencing process.

[0113] Optionally, an embodiment of the present invention further provides a multi-channel nanopore sensor insertion device, which can be used to perform the multi-channel nanopore sensor insertion method provided by any embodiment of the present invention. Figure 9 A schematic structural diagram of a multi-channel nanopore sensor according to an embodiment of the present invention, referring to Figure 9 , the device comprises:

[0114] The detection unit 21 is used to detect whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore.

[0115] The switch switching unit 22 is configured to control the corresponding multiplexing switch to switch the preset channel to the target channel when detecting that the preset channel is inserted into the nanopore.

[0116] Among them, the detection module 21 can be integrated into Figure 1 In the signal detection module 14 of the system shown, the switch unit 22 can be integrated into the control module 15 .

[0117] The insertion device of the multi-channel nanopore sensor provided in this embodiment and the insertion method of the multi-channel nanopore sensor provided in any embodiment of the present invention belong to the same inventive concept and have the same beneficial effects, which will not be repeated here.

[0118] Optionally, an embodiment of the present invention further provides an electronic device, Figure 10 A schematic diagram of the structure of an electronic device provided by an embodiment of the present invention, referring to Figure 10 The electronic device includes a processor 31, a memory 32, an input device 33 and an output device 34; the number of the processor 31 can be one or more, Figure 10 Only one processor 31 is shown. The processor 31 , the memory 32 , the input device 33 , and the output device 34 may be connected via a bus or other means.

[0119] The memory 32 is a computer-readable storage medium that can be used to store software programs, computer-executable programs, and modules, such as program instructions / modules corresponding to the jacking method of the multi-channel nanopore sensor in the embodiment of the present invention (for example, Figure 9 The processor 31 executes various functional applications and data processing of the electronic device by running the software programs, instructions and modules stored in the memory 32, that is, realizes the above-mentioned jacking method of the multi-channel nanopore sensor.

[0120] The memory 32 may mainly include a program storage area and a data storage area, wherein the program storage area may store an operating system and at least one application required for a function; the data storage area may store data created based on the use of the terminal, etc. In addition, the memory 32 may include a high-speed random access memory and may also include a non-volatile memory, such as at least one disk storage device, a flash memory device, or other non-volatile solid-state storage device. In some instances, the memory 32 may further include a memory remotely located relative to the processor 31, and these remote memories may be connected to the electronic device via a network. Examples of the above-mentioned network include but are not limited to the Internet, an intranet, a local area network, a mobile communication network, and combinations thereof. The input device 33 may be used to receive input digital or character information, and to generate key signal input related to user settings and function control of the electronic device. The output device 34 may include a display screen for outputting information processed and controlled by the electronic device.

[0121] In some examples, the electronic device may be a server or a computer (such as a PC), wherein the server may be one or a server cluster consisting of multiple servers.

[0122] Optionally, an embodiment of the present invention further provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the insertion method for a multi-channel nanopore sensor as described in any embodiment of the present invention. It should be understood that the computer-readable storage medium provided in this embodiment and the computer program stored thereon are not limited to the operations described above, but can also perform related operations in the insertion method for a multi-channel nanopore sensor provided in any embodiment of the present invention.

[0123] Through the above description of the implementation method, technical personnel in the relevant field can clearly understand that the present invention can be implemented with the help of software and necessary general hardware, such as the power supply module 13 in the jack system, the multiplexing switch 12 and other hardware devices. Of course, it can also be implemented through hardware, but in many cases the former is a better implementation method.

[0124] It should be understood that the various forms of the processes shown above can be used to reorder, add, or delete steps. For example, the steps described in the present invention can be performed in parallel, sequentially, or in a different order, as long as the desired results of the technical solution of the present invention can be achieved. This is not limited herein.

[0125] The above specific embodiments do not limit the scope of protection of the present invention. Those skilled in the art will appreciate that various modifications, combinations, sub-combinations, and substitutions may be made based on design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention are intended to be included within the scope of protection of the present invention.

Claims

1. A method for inserting a multi-channel nanopore sensor, characterized in that: Each group of channels of the multi-channel nanopore sensor to be inserted is connected to a multiplex switch respectively. The insertion method of the multi-channel nanopore sensor includes: respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore; When it is detected that the preset channel is inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the preset channel to the target channel.

2. The method for inserting a multi-channel nanopore sensor according to claim 1, characterized in that: The step of respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore comprises: detecting the current values ​​in the preset channels in the same group of channels once every first preset time; Whether the preset channel is inserted into the nanopore is determined according to the current value; if the current value is greater than or equal to a current threshold, it is determined that the preset channel is inserted into the nanopore.

3. The method for inserting a multi-channel nanopore sensor according to claim 2, characterized in that: The insertion method of the multi-channel nanopore sensor further includes: If the preset channel is not detected to be inserted into the nanopore for a second preset time, controlling the corresponding multiplexing switch to switch the preset channel to the target channel; Wherein, the second preset time is greater than the first preset time; The insertion method of the multi-channel nanopore sensor further includes: When the preset channel is switched to the last channel in the same group of channels and the jack detection is completed, the multiplexing switch is controlled to be turned off.

4. The method for inserting a multi-channel nanopore sensor according to claim 3, characterized in that: Each channel group of the multi-channel nanopore sensor includes four channels, and the insertion method of the multi-channel nanopore sensor includes: detecting whether a first channel in each group of channels of the multi-channel nanopore sensor is inserted into a nanopore at every first preset time; If the first channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the first channel to the second channel; if the first channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the first channel to the second channel; detecting whether the second channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time; If the second channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the second channel to the third channel; if the second channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the second channel to the third channel; detecting whether the third channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time; If the third channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to switch the third channel to the fourth channel; if the third channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to switch the third channel to the fourth channel; detecting whether the fourth channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore at every first preset time; If the fourth channel is detected to be inserted into the nanopore, the corresponding multiplexing switch is controlled to be turned off; if the fourth channel is not detected to be inserted into the nanopore for the second preset time, the corresponding multiplexing switch is controlled to be turned off.

5. The method for inserting a multi-channel nanopore sensor according to claim 1, characterized in that: The insertion method of the multi-channel nanopore sensor further includes: Whenever it is detected that the preset channel is inserted into the nanopore, counting the insertion ratio of the multi-channel nanopore sensor; Preferably, after a third preset time from the start of insertion, each time it is detected that the preset channel is inserted into the nanopore, the insertion ratio of the multi-channel nanopore sensor is counted.

6. The method for inserting a multi-channel nanopore sensor according to claim 5, characterized in that: The insertion method of the multi-channel nanopore sensor further includes: When all channels in the channel group are switched to the last channel, if the insertion ratio is less than the preset ratio, the channel in the same channel group that is not inserted with the nanopore is used as the preset channel, and cyclic detection is performed, and channel switching is performed between the channels that are not inserted with the nanopore; Until the insertion ratio of the multi-channel nanopore sensor is greater than or equal to the preset ratio, the multiplexing switches corresponding to each group of channels are controlled to be turned off.

7. The method for inserting a multi-channel nanopore sensor according to claim 1, characterized in that: Before respectively detecting whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore, the method further includes: adding a nanopore protein solution to the multi-channel nanopore sensor; Controlling the multiplexing switch to switch each group of channels to the preset channel, and applying a fixed voltage to the preset channel; Preferably, the insertion method of the multi-channel nanopore sensor further comprises: When the insertion is completed, the nanopore protein solution in the multi-channel nanopore sensor is replaced.

8. A multi-channel nanopore sensor jack device, characterized in that: include: a detection unit, configured to respectively detect whether a preset channel in each group of channels of the multi-channel nanopore sensor is inserted into the nanopore; The switch switching unit is configured to control a corresponding multiplexing switch to switch the preset channel to a target channel when detecting that the preset channel is inserted into the nanopore.

9. An electronic device, characterized in that: include: one or more processors; a storage device for storing one or more programs; When the one or more programs are executed by the one or more processors, the one or more processors are enabled to implement the jack method for the multi-channel nanopore sensor according to any one of claims 1 to 7.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the program is executed by a processor, the pore insertion method of the multi-channel nanopore sensor according to any one of claims 1 to 7 is implemented.

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