Control method, gene sequencer, and storage medium
By adopting automated liquid addition, rehydration and liquid replacement strategies in the gene sequencing system, the reagent tank operation is automatically controlled according to the nucleic acid sequencing process and real-time conditions, the problem of inefficiency in the existing technology is solved, and the operation efficiency of reagent tank is improved. Sequencing accuracy.
Patent Information
- Application Number
- PCT/CN2024/096295
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-06-15
- Filing Date
- 2024-05-30
- Publication Date
- 2024-12-19
AI Technical Summary
The existing gene sequencing system is less efficient in the reagent tank rehydration, addition and replacement process, and mainly relies on manual or semi-automatic methods, resulting in cumbersome and inefficient operations.
Adopt preset liquid addition strategy, liquid replenishment strategy or liquid replacement strategy to automatically perform liquid addition, replenishment, liquid replenishment or liquid replacement by real-time judgment of the trigger conditions of the reagent tank, including taking photos based on the nucleic acid sequencing process stage, liquid level sensor feedback, and optical machine device Control the parameters such as quality to ensure automatic rehydration, addition and replacement of the reagent tank.
The reagent tank replenishment, addition and replacement efficiency are improved, manual operation is reduced, and the utilization rate and sequencing accuracy of the reagent tank are improved.
Smart Images

Figure CN2024096295_19122024_PF_FP_ABST
Abstract
Description
Control method, gene sequencer and storage medium
[0001] The present invention claims priority to the Chinese patent application filed with the Patent Office of China on June 15, 2023, with application number 202310714815.5 and application name “Control Method, Gene Sequencer and Storage Medium”, the entire contents of which are incorporated herein by reference. Technical Field
[0002] The present application relates to the field of gene sequencing technology, and in particular to a control method, a gene sequencer, and a storage medium. Background Art
[0003] The second-generation gene sequencing technology has been widely used in whole genome sequencing, transcriptome sequencing, metagenomic sequencing, etc. It is a powerful tool for analyzing biochemical evolution and classification, studying genes related to diseases such as cancer and autism, and conducting in vitro diagnosis.
[0004] Current gene sequencing systems include a biochemical reaction unit and an optical detection unit. The biochemical reaction unit is used to allow open immersion of gene sequencing chips, enabling repeated use of reagents. Specifically, the biochemical reaction unit includes a reagent tank for open immersion of the gene sequencing chips. The gene sequencing system allows for the filling and draining of the reagent tank, facilitating the infusion of reagents before the reaction, the replenishment of reagents during the reaction, and the removal of reagents after the entire sequencing process is complete. The optical detection unit is used to perform optical inspection of the gene sequencing chips.
[0005] At present, the methods for replenishing, adding or replacing the reagent tank of an open fluid system are mainly to replenish, add or replace the reagent tank by pure manual means, or to replenish, add or replace the reagent tank by semi-automatic means, resulting in low efficiency in replenishing, adding or replacing the reagent tank. Technical issues
[0006] In view of this, the present invention aims to solve at least one of the problems in the related art to a certain extent. To this end, the purpose of this application is to provide a control method, a gene sequencer and a storage medium. Technical Solutions
[0007] The present application provides a control method. The control method includes:
[0008] According to the preset liquid addition strategy, liquid replenishment strategy or liquid replacement strategy, it is judged in real time whether the trigger conditions corresponding to the addition, replenishment or liquid replacement of the reagent tank are met;
[0009] When the trigger condition is reached, the reagent tank is added with liquid, supplemented with liquid or replaced with liquid.
[0010] In this way, the control method of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenish liquid or replace liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, addition or replacement of liquid in the reagent tank and improve the efficiency of liquid replenishment, addition or replacement of liquid in the reagent tank.
[0011] In certain embodiments, the liquid addition strategy includes adding different target reagents and target reagent amounts to the reagent tank according to different sequencing stages of the nucleic acid sequencing process. The control method includes:
[0012] determining in real time the current sequencing stage of the nucleic acid sequencing process;
[0013] Determining whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent; and,
[0014] When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the target reagent is added to the reagent tank according to the target reagent volume.
[0015] In this way, the control method of the present application determines the current sequencing stage of the nucleic acid sequencing process in real time, and judges whether the current sequencing stage has reached the target sequencing corresponding to the target reagent, so that when the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the target reagent is added to the reagent tank according to the target reagent volume. Then, according to different sequencing stages of the nucleic acid sequencing process, different target reagent volumes of target reagents can be automatically added to the reagent tank to avoid other reagents being exposed to the air too early, resulting in weakened biochemical effects.
[0016] In certain embodiments, the fluid replenishment strategy includes a strategy of replenishing fluid according to a first time interval, and replenishing fluid to the reagent tank when the trigger condition is met includes:
[0017] The reagent tank is replenished with liquid according to the first time interval, taking the liquid addition time as a starting point.
[0018] In this way, the control method of the present application can use the liquid addition time as the starting timing point and automatically replenish the reagent tank according to the first time interval, so that the user can set different liquid addition times according to different types of reagent tanks and automatically replenish the reagent tank.
[0019] In certain embodiments, replenishing the reagent tank with liquid when the trigger condition is met further comprises:
[0020] The reagent tank is replenished with liquid according to the first time interval, taking the previous liquid replenishment time as the starting timing point.
[0021] In this way, the control method of the present application can use the last refilling time as the starting timing point, and refill the reagent tank according to the first time interval, thereby automatically refilling the reagent tank.
[0022] In certain embodiments, the rehydration strategy includes a strategy for rehydration based on the number of soaking reactions of the sequencing chip in the reagent tank. The control method includes:
[0023] determining in real time whether the number of soaking reactions is greater than or equal to a first threshold;
[0024] When the number of immersion reactions is greater than or equal to the first threshold, the reagent tank is replenished with liquid.
[0025] In this way, the control method of the present application can set different first thresholds according to reagents of different viscosities, and judge in real time whether the number of immersion reactions of the sequencing chip is greater than or equal to the first threshold, so as to automatically replenish the reagent tank when the number of immersion reactions is greater than or equal to the first threshold, thereby improving the efficiency of replenishing the reagent tank.
[0026] In certain embodiments, the fluid replenishment strategy includes a fluid replenishment strategy based on an electrical signal fed back by a liquid level sensor, wherein the liquid level sensor is provided on a hose outside the reagent tank and connected to the reagent tank, and the control method includes:
[0027] Acquiring the electrical signal output by the liquid level sensor in real time;
[0028] The reagent tank is replenished with liquid according to the electrical signal.
[0029] In this way, the control method of the present application can configure different reagent replenishment volumes for reagent tanks with different liquid levels according to the electrical signal output by the liquid level sensor.
[0030] In certain embodiments, the fluid replenishment strategy includes a fluid replenishment strategy based on feedback from the photographing quality of the optical mechanical device, and the control method includes:
[0031] Acquiring in real time a plurality of images corresponding to a preset number of rows and columns by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical mechanical device; the plurality of images corresponding to the preset number of rows are a plurality of images corresponding to grids divided from the 1st row to the nth row in a vertical direction of the reagent tank from bottom to top on the sequencing chip, where n is greater than 1;
[0032] Calculating the brightness of the multiple images according to a preset algorithm;
[0033] If the brightness of the multiple images corresponding to the nth row is lower than a preset brightness value, the reagent tank is replenished with liquid.
[0034] In this way, the control method of the present application can obtain in real time multiple images corresponding to a preset number of rows and columns obtained by the optical-mechanical device taking pictures of the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction, and calculate the brightness of the multiple images according to a preset algorithm. If the brightness of the multiple images corresponding to the nth row on the sequencing chip, that is, the top row of the sequencing chip, which is divided from bottom to top in the vertical direction of the reagent tank, is lower than the preset brightness value, it is considered that the reagent liquid level in the reagent tank is insufficient, and the reagent tank is automatically replenished.
[0035] In certain embodiments, the fluid replacement strategy includes a fluid replacement strategy according to a second time interval, and the control method includes:
[0036] The liquid addition time is used as a starting point for timing, and the liquid in the reagent tank is replaced according to the second time interval.
[0037] In this way, the control method of the present application can use the liquid addition time as the starting timing point and replace the liquid in the reagent tank according to the second time interval, so that the user can set different liquid addition times according to different types of reagent tanks and automatically replace the liquid in the reagent tank.
[0038] In certain embodiments, the liquid replacement strategy includes a liquid replacement strategy based on the number of immersion reactions of the sequencing chip in the reagent tank, and the control method includes:
[0039] determining in real time whether the number of soaking reactions is greater than or equal to a second threshold;
[0040] When the number of immersion reactions is greater than or equal to the second threshold, the liquid in the reagent tank is replaced.
[0041] In this way, the control method of the present application can set different second thresholds according to reagents of different viscosities, and judge in real time whether the number of immersion reactions of the sequencing chip is greater than or equal to the second threshold, so as to automatically replace the liquid in the reagent tank when the number of immersion reactions is greater than or equal to the second threshold, thereby improving the efficiency of the reagent tank liquid replacement.
[0042] In certain embodiments, the fluid replacement strategy includes a fluid replacement strategy based on feedback from an optical-mechanical device regarding photographic quality, and the control method includes:
[0043] Acquiring in real time a plurality of images corresponding to a preset number of rows and columns obtained by photographing the soaking reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical-mechanical device;
[0044] Calculating the brightness of the multiple images according to a preset algorithm, and calculating an average brightness of the multiple images;
[0045] If the average brightness of the current round of images is less than the average brightness of the previous round of images, the liquid in the reagent tank is replaced.
[0046] In this way, the control method of the present application can obtain in real time multiple images corresponding to a preset number of rows and columns by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction, and after calculating the brightness of the multiple images according to the preset algorithm, calculate the brightness average of the multiple images. When the brightness average of the current round of images is less than the brightness average of the previous round of images, the reagent tank can be automatically replaced.
[0047] In certain embodiments, the fluid replacement strategy includes a fluid replacement strategy according to different biochemical stages, and the control method includes:
[0048] Determine the current sequencing stage of the nucleic acid sequencing process in real time;
[0049] Determining whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent;
[0050] When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the original liquid in the reagent tank is drained, and the target reagent is added to the reagent tank according to the target reagent volume.
[0051] In this way, the control method of the present application determines the current sequencing stage of the nucleic acid sequencing process in real time and judges whether the current sequencing stage has reached the target sequencing corresponding to the target reagent, so that when the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the original liquid in the reagent tank is emptied and the target reagent is added to the reagent tank according to the target reagent volume. Then, according to different sequencing stages of the nucleic acid sequencing process, the original liquid in the reagent tank can be automatically emptied and the target reagent can be added to the reagent tank according to the target reagent volume to improve the reuse rate of the reagent tank.
[0052] The present application also provides a gene sequencer. The gene sequencer includes a control device and a reagent tank. The control device includes a judgment module and an execution module. The judgment module is configured to determine in real time whether a trigger condition corresponding to adding, replenishing, or replacing liquid in the reagent tank has been met based on a preset liquid addition strategy, liquid replenishment strategy, or liquid replacement strategy; the execution module is configured to add, replenish, or replace liquid in the reagent tank when the trigger condition is met.
[0053] In this way, the gene sequencer of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenishing liquid or replacing liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, addition or replacement of liquid in the reagent tank, thereby improving the efficiency of liquid replenishment, addition or replacement of liquid in the reagent tank.
[0054] The present application also provides a computer-readable storage medium storing a computer program, which, when executed by one or more processors, implements the control method described in the above embodiment.
[0055] In this way, the computer-readable storage medium of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenishing liquid or replacing liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, adding liquid or replacing liquid in the reagent tank, and improve the efficiency of liquid replenishment, adding liquid or replacing liquid in the reagent tank. Beneficial effects
[0056] The above-mentioned control method can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenishing liquid or replacing liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, adding liquid or replacing liquid in the reagent tank, thereby improving the efficiency of liquid replenishment, adding liquid or replacing liquid in the reagent tank.
[0057] The above-mentioned gene sequencer and computer-readable storage medium have the same technical concept as the corresponding control method embodiments, and thus have at least the same technical effects.
[0058] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0059] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:
[0060] FIG1 is a flow chart of a control method in some embodiments of the present application;
[0061] FIG2 is a schematic structural diagram of a control device in certain embodiments of the present application;
[0062] FIG3 is a schematic structural diagram of a biochemical device in certain embodiments of the present application;
[0063] FIG4 is a second flow chart of a control method in certain embodiments of the present application;
[0064] FIG5 is a third flow chart of a control method in certain embodiments of the present application;
[0065] FIG6 is a fourth flow chart of a control method in certain embodiments of the present application;
[0066] FIG7 is a fifth flow chart of a control method in certain embodiments of the present application;
[0067] FIG8 is a schematic diagram of a sequencing chip divided into grids having a preset number of rows and a preset number of columns in certain embodiments of the present application;
[0068] FIG9 is a sixth flow chart of a control method in certain embodiments of the present application;
[0069] FIG10 is a seventh flow chart of a control method in certain embodiments of the present application;
[0070] FIG11 is an eighth flowchart of the control method in certain embodiments of the present application. Modes for Carrying Out the Invention
[0071] The embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present application, and should not be understood as limiting the present application.
[0072] In the description of this application, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the described features. In the description of this application, "plurality" means two or more, unless otherwise expressly and specifically defined.
[0073] In the description of this application, it should be noted that, unless otherwise expressly specified or limited, the terms "installed," "connected," and "connected" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections, electrical connections, or connections that can communicate with each other; they can refer to direct connections or indirect connections through an intermediate medium; they can refer to internal connectivity between two components or interactions between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on specific circumstances.
[0074] The disclosure below provides many different embodiments or examples for implementing different structures of the present application. In order to simplify the disclosure of the present application, the components and settings of specific examples are described below. Of course, these are merely examples and are not intended to limit the present application. In addition, the present application may repeat reference numbers and / or reference letters in different examples. Such repetition is for the purpose of simplicity and clarity and does not in itself indicate the relationship between the various embodiments and / or settings discussed.
[0075] The embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present application, and should not be understood as limiting the present application.
[0076] In the related art, the fluid in the reagent tank of the biochemical device is an open fluid, and some reagent tanks need to maintain a certain high temperature, such as a high temperature of about 60 degrees, so evaporation will occur. In addition, since the sequencing chip is transferred between open reagent tanks, some reagents will adhere to the surface of the sequencing chip. During the transfer of the sequencing chip, reagent splashing may occur. The above three problems will all lead to a reduction in the actual amount of reagent in the reagent tank, so rehydration is required.
[0077] Furthermore, after multiple rounds of sequencing chip reactions within the same reagent reservoir, the concentration of the effective reactants decreases, necessitating liquid replacement. Furthermore, to maximize reservoir utilization, some reservoirs are filled with different reagents at different reaction stages, also requiring liquid replacement.
[0078] That is, at present, the method for replenishing, adding or changing the liquid of the reagent tank of the open fluid system is mainly to replenish, add or change the liquid of the reagent tank by a purely manual method, or to replenish, add or change the liquid of the reagent tank by a semi-automatic method, resulting in low efficiency in replenishing, adding or changing the liquid of the reagent tank.
[0079] In view of this, please refer to Figure 1, the present application provides a control method. The control method includes:
[0080] 01: According to the preset liquid addition strategy, liquid replenishment strategy or liquid replacement strategy, it is judged in real time whether the trigger conditions corresponding to liquid addition, liquid replenishment or liquid replacement of the reagent tank are met.
[0081] 02: Add, replenish or replace the liquid in the reagent tank when the trigger condition is met.
[0082] 2 , the present application further provides a control device 10 . The control device 10 includes a determination module 11 and an execution module 12 .
[0083] Step 01 can be implemented by the judgment module 11, and step 02 can be implemented by the execution module 12. Specifically, the judgment module 11 is configured to determine in real time whether a trigger condition for adding, replenishing, or replacing the reagent tank has been met based on a preset liquid addition strategy, liquid replenishment strategy, or liquid replacement strategy. The execution module 12 is configured to add, replenish, or replace the reagent tank when the trigger condition is met.
[0084] Please refer to Figure 3. The control method and device of the present application can be applied to the biochemical device 20 shown in Figure 3. The biochemical device 20 includes a reagent tank 21, a sequencing chip 23, a liquid level sensor 25 and a hose 27. The reagent tank 21 is used to hold reagents and the sequencing chip 23, and to perform biochemical reactions. The liquid level sensor 25 is located outside the reagent tank 21 and is arranged on a hose 27 that is connected to the reagent tank 21. The liquid level sensor 25 is used to detect the liquid level of the reagent tank 21. The hose 27 is arranged on the outer side wall of the reagent tank 21, one end of the hose 27 is connected to the bottom of the reagent tank 21, and the other end of the hose 27 is flush with the opening of the reagent tank 21. The hose 27 is used to display the liquid level in the reagent tank.
[0085] That is, when the triggering conditions of the liquid addition strategy are determined to be met according to the liquid addition strategy, liquid can be automatically added to the reagent tank 21. When the triggering conditions of the liquid replenishment strategy are determined to be met according to the liquid replacement strategy, liquid can be automatically replenished to the reagent tank 21. When the triggering conditions of the liquid replacement strategy are determined to be met according to the liquid replacement strategy, liquid can be automatically replaced in the reagent tank 21.
[0086] 3 , the reagent tanks 21 may include a first reagent tank 211, a second reagent tank 212, a second reagent tank 213, a fourth reagent tank 214, and a fifth reagent tank 215. In other words, different reagent tanks 21 may contain different reagents to perform different biochemical reactions on the sequencing chip.
[0087] It should be noted that when the present application determines that the triggering conditions of the liquid addition strategy, the liquid replenishment strategy or the liquid replacement strategy are met, the reagent tank will be automatically added, replenished or replaced. It will automatically reset and re-determine whether the triggering conditions of the liquid addition strategy, the liquid replenishment strategy or the liquid replacement strategy are met according to the triggering conditions of the liquid addition strategy, the liquid replenishment strategy or the liquid replacement strategy, and re-automatically add, replenish or replace the reagent tank to realize intelligent liquid addition, replenishment or replacement of the reagent tank.
[0088] In this way, the control method of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenish liquid or replace liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, addition or replacement of liquid in the reagent tank and improve the efficiency of liquid replenishment, addition or replacement of liquid in the reagent tank.
[0089] Referring to FIG4 , in certain embodiments, the liquid addition strategy includes strategies for adding different target reagents and target reagent amounts to the reagent tanks according to different sequencing stages of the nucleic acid sequencing process. The control method includes:
[0090] 011: Determine the current sequencing stage of the nucleic acid sequencing workflow in real time.
[0091] 012: Determine whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent.
[0092] 021: When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, add the target reagent to the reagent tank according to the target reagent volume.
[0093] Referring to Figure 2 , steps 011 and 012 can be implemented by determination module 11. Step 021 can be implemented by execution module 12. Specifically, determination module 11 is configured to determine the current sequencing stage of the nucleic acid sequencing process in real time and determine whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent. Execution module 12 is configured to add the target reagent to the reagent reservoir according to the target reagent volume when the current sequencing stage has reached the target sequencing stage corresponding to the target reagent.
[0094] Specifically, the nucleic acid sequencing process may include a polymerase chain reaction stage, a single-strand sequencing stage, and a double-strand sequencing stage. The target reagents may include relevant reagents corresponding to the polymerase chain reaction stage, relevant reagents corresponding to the single-strand sequencing stage, and relevant reagents corresponding to the double-strand sequencing stage. The target reagent volume may be, for example, 28 mL, 29 mL, 30 mL, 31 mL, 32 mL, 33 mL, 34 mL, and 35 mL, without limitation herein.
[0095] For example, when the current sequencing stage of the nucleic acid sequencing process is determined to be the start of the polymerase chain reaction stage, it can first be determined based on the polymerase chain reaction stage that a target amount of relevant reagents corresponding to the polymerase chain reaction stage needs to be automatically added to the reagent tank. Then, the target amount of relevant reagents corresponding to the polymerase chain reaction stage is automatically added to the reagent tank. The relevant reagents corresponding to the polymerase chain reaction stage can be, for example, a polymerase chain reaction buffer, a sample reagent, a denaturing reagent, or other relevant reagents, without limitation herein.
[0096] When the current sequencing stage of the nucleic acid sequencing process is determined to be the start of a single-strand sequencing stage, a target amount of relevant reagents corresponding to the single-strand sequencing stage may first be automatically added to the reagent reservoir based on the single-strand sequencing stage. Then, the determined target amount of relevant reagents corresponding to the single-strand sequencing stage may be automatically added to the reagent reservoir. The relevant reagents corresponding to the single-strand sequencing stage may be, for example, pre-cleaning reagents, synthesis reagents, cleaning reagents, or other relevant reagents, without limitation herein.
[0097] When the current sequencing stage of the nucleic acid sequencing process is determined to be the start of the two-strand sequencing stage, a target amount of relevant reagents corresponding to the two-strand sequencing stage may first be automatically added to the reagent reservoir based on the two-strand sequencing stage. Then, the determined target amount of relevant reagents corresponding to the two-strand sequencing stage may be automatically added to the reagent reservoir. The relevant reagents corresponding to the two-strand sequencing stage may be, for example, denaturing reagents, washing reagents, or other relevant reagents, without limitation herein.
[0098] In this way, the control method of the present application determines the current sequencing stage of the nucleic acid sequencing process in real time, and judges whether the current sequencing stage has reached the target sequencing corresponding to the target reagent, so that when the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the target reagent is added to the reagent tank according to the target reagent volume. Then, according to different sequencing stages of the nucleic acid sequencing process, different target reagent volumes of target reagents can be automatically added to the reagent tank to avoid other reagents being exposed to the air too early, resulting in weakened biochemical effects.
[0099] In certain embodiments, the fluid replenishment strategy includes a strategy for replenishing fluid according to a first time interval. Step 02 includes:
[0100] 022: Taking the liquid addition time as the starting point, the reagent tank is replenished with liquid according to the first time interval.
[0101] 2 , step 022 can be implemented by the execution module 12. That is, the execution module 12 is configured to use the liquid addition time as a starting point and replenish the reagent tank with liquid according to the first time interval.
[0102] Wherein, the first time interval can be, for example, 4.5min, 4.6min, 4.7min, 4.8min, 4.9min, 5min, 5.1min, 5.2min, 5.3min, and 5.4min, without limitation hereof. The user can set the first time interval by the timer provided in the software system. The reagent tank can include a constant temperature reagent tank and a normal temperature reagent tank. Wherein, the constant temperature reagent tank refers to a reagent tank that needs to be heated to a certain temperature, and the temperature of the constant temperature reagent tank can be, for example, 45 degrees, 50 degrees, 60 degrees or other temperature values, without limitation hereof. The normal temperature reagent tank refers to a reagent tank that does not need to be heated to a certain temperature, and the temperature of the normal temperature reagent tank can be, for example, 25 degrees.
[0103] That is, the present application can use the liquid addition time as the starting point to time the reagent tank in real time. When the time interval between the current time and the liquid addition time is the first time interval, the reagent tank is automatically replenished with a preset amount of reagent, and the reagent tank is subsequently automatically replenished at the first time interval. The preset reagent amount can be, for example, 100 microliters, 111 microliters, 112 microliters, 113 microliters, 114 microliters, 115 microliters, 116 microliters, 117 microliters, 118 microliters, 119 microliters, and 200 microliters, without limitation.
[0104] For example, when the first time interval for replenishing the normal temperature reagent tank is 5 minutes, the normal temperature reagent tank can be timed in real time with the liquid addition time as the starting point. When the timing reaches 5 minutes between the current time and the liquid addition time interval, the normal temperature reagent tank is automatically replenished, and the reagent tank is subsequently automatically replenished at the first time interval of 5 minutes.
[0105] For another example, when the first time interval for replenishing the constant temperature reagent tank is 4.6 minutes, the constant temperature reagent tank can be timed in real time with the liquid addition time as the starting point. When the timing reaches 4.6 minutes between the current time and the liquid addition time interval, the normal temperature reagent tank is automatically replenished, and the reagent tank is subsequently automatically replenished at the first time interval of 4.6 minutes.
[0106] It can be understood that since the evaporation rate of the reagent in the constant temperature reagent tank is faster than that of the reagent in the normal temperature reagent tank, the interval time for replenishing the constant temperature reagent tank according to the first time interval should be shorter than the interval time for replenishing the normal temperature reagent tank according to the first time interval.
[0107] In this way, the control method of the present application can use the liquid addition time as the starting timing point and automatically replenish the reagent tank according to the first time interval, so that the user can set different liquid addition times according to different types of reagent tanks and automatically replenish the reagent tank.
[0108] In some embodiments, step 02 includes:
[0109] 023: The last refilling time is used as the starting point, and the reagent tank is refilled according to the first time interval.
[0110] 2 , step 023 can be implemented by the execution module 12. That is, the execution module 12 is configured to use the last refilling time as a starting point and refill the reagent tank according to the first time interval.
[0111] That is, the present application can use the rehydration time as the starting point to time the reagent tank in real time. When the time interval between the current time and the rehydration time is the first time interval, the reagent tank is automatically rehydrated, and the reagent tank is subsequently automatically rehydrated at the first time interval.
[0112] For example, when the first time interval for replenishing the normal temperature reagent tank is 5.2 minutes, the normal temperature reagent tank can be timed in real time with the replenishment time as the starting point. When the timing reaches 5.2 minutes between the current time and the replenishment time interval, the normal temperature reagent tank is automatically replenished, and the reagent tank is subsequently automatically replenished at the first time interval of 5.2 minutes.
[0113] For another example, when the first time interval for replenishing the constant temperature reagent tank is 4.5 minutes, the constant temperature reagent tank can be timed in real time with the replenishment time as the starting point. When the timing reaches 4.5 minutes between the current time and the replenishment time interval, the normal temperature reagent tank is automatically replenished, and the reagent tank is subsequently automatically replenished at the first time interval of 4.5 minutes.
[0114] In this way, the control method of the present application can use the last refilling time as the starting timing point, and refill the reagent tank according to the first time interval, thereby automatically refilling the reagent tank.
[0115] Referring to FIG5 , in certain embodiments, the rehydration strategy includes a strategy for rehydrating the reagent tank according to the number of soaking reactions of the sequencing chip. The control method includes:
[0116] 013: Determine in real time whether the number of immersion reactions is greater than or equal to a first threshold.
[0117] 024: When the number of immersion reactions is greater than or equal to the first threshold, the reagent tank is replenished with liquid.
[0118] Referring to Figure 2 , step 013 can be implemented by determination module 11. Step 024 can be implemented by execution module 12. Specifically, determination module 11 is configured to determine in real time whether the number of immersion reactions is greater than or equal to a first threshold. Execution module 12 is configured to replenish the reagent tank with liquid if the number of immersion reactions is greater than or equal to the first threshold.
[0119] The first threshold may be, for example, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times or other times, which is not limited here.
[0120] Specifically, when nucleic acid sequencing begins, it can be determined in real time whether the number of immersion reactions of the sequencing chip in the time slot is greater than or equal to a first threshold, and when the number of immersion reactions is greater than or equal to the first threshold, the reagent slot is automatically replenished.
[0121] It should be noted that, due to the different viscosities of different reagents, the first threshold values set for different reagents will also vary. That is, the higher the viscosity of the reagent, the lower the first threshold value set. For example, as shown in FIG3 , if reagent A1 and reagent A2 are placed in the first reagent tank 211 and the second reagent tank 212, respectively, the viscosity of reagent A1 is greater than that of reagent A2, so the first threshold value set for reagent A1 is lower than the first threshold value set for reagent A2.
[0122] In this way, the control method of the present application can set different first thresholds according to reagents of different viscosities, and judge in real time whether the number of immersion reactions of the sequencing chip is greater than or equal to the first threshold, so as to automatically replenish the reagent tank when the number of immersion reactions is greater than or equal to the first threshold, thereby improving the efficiency of replenishing the reagent tank.
[0123] Referring to FIG6 , in certain embodiments, the fluid replenishment strategy includes a fluid replenishment strategy based on an electrical signal fed back by a liquid level sensor 25. The liquid level sensor 25 is disposed on a hose 27 outside the reagent tank and connected to the reagent tank (as shown in FIG3 ). The control method includes:
[0124] 014: Get the electrical signal output by the liquid level sensor in real time.
[0125] 025: Refill the reagent tank according to the electrical signal.
[0126] 2 , step 014 can be implemented by the judgment module 11. Step 025 can be implemented by the execution module 12. That is, the judgment module 11 is used to obtain the electrical signal output by the liquid level sensor 25 in real time. The execution module 12 is used to replenish the reagent tank according to the electrical signal.
[0127] Specifically, as shown in FIG3 , when the sequencing chip 23 is inserted into the reagent tank 21, the liquid level in the reagent tank 21 will rise. At this time, the liquid level sensor 25 can detect whether the liquid level in the reagent tank 21 has risen to the height of the installation position of the liquid level sensor 25. If the liquid level sensor 25 detects that the liquid level in the reagent tank 21 has not risen to the height of the installation position of the liquid level sensor 25, the liquid level sensor 25 outputs an electrical signal. At this time, the reagent tank 21 can be automatically replenished with liquid based on the electrical signal output by the liquid level sensor 25. That is, for example, if the installation height of the liquid level sensor 25 is the position where the liquid level of the reagent in the reagent tank 21 is 10 ml, if the liquid level sensor 25 detects a signal, it can be determined that the liquid level of the reagent in the reagent tank 21 has reached 10 ml and no liquid replenishment is required. Conversely, if the liquid level sensor 25 does not detect a signal, it can be determined that the liquid level of the reagent in the reagent tank is less than 10 ml and the reagent tank 21 needs to be automatically replenished with liquid.
[0128] In this way, the control method of the present application can configure different reagent replenishment volumes for reagent tanks with different liquid levels according to the electrical signal output by the liquid level sensor 25 .
[0129] Referring to FIG. 7 , in certain embodiments, the fluid replenishment strategy includes a fluid replenishment strategy based on feedback from the photo quality of the optical-mechanical device. The control method includes:
[0130] 015: Acquire multiple images corresponding to a preset number of rows and columns by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction in real time using an optical-mechanical device; the multiple images corresponding to the preset number of rows are multiple images corresponding to grids on the sequencing chip divided from the 1st row to the nth row from bottom to top in the vertical direction of the reagent tank, where n is greater than 1.
[0131] 016: Calculate the brightness of multiple images according to a preset algorithm.
[0132] 026: If the brightness of the multiple images in the nth row is lower than the preset brightness value, the reagent tank is replenished with liquid.
[0133] Please refer to Figure 2. Steps 015 and 016 can be implemented by the judgment module 11. Step 026 can be implemented by the execution module 12. That is, the judgment module 11 is used to obtain in real time the images corresponding to the preset number of rows and the preset number of columns obtained by the optical mechanical device taking pictures of the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction; the multiple images corresponding to the preset number of rows are the multiple images corresponding to the grids divided from the 1st row to the nth row from bottom to top in the vertical direction of the reagent tank on the sequencing chip, where n is greater than 1; the brightness of the multiple images is calculated according to the preset algorithm. The execution module 12 is used to replenish the reagent tank if the brightness of the multiple images in the nth row is lower than the preset brightness value.
[0134] Among them, the optical-mechanical device refers to a device assembled together by a light source, a lens, a reflector, and an imaging module. The optical-mechanical device can be, for example, a camera. As shown in Figure 8, before the optical-mechanical device takes a picture, a grid of a preset number of rows multiplied by a preset number of columns can be divided on the immersion reaction surface 231 of the sequencing chip, and then the optical-mechanical device takes a picture of each grid divided on the immersion reaction surface 231 of the sequencing chip to obtain multiple images, that is, at this time, an image of the preset number of rows multiplied by the preset number of columns can be obtained. For example, the preset number of rows can be 100 rows, and the preset number of columns can be 100 columns, so that 100 times 100 images can be obtained. The preset number of rows and the preset number of columns can also be other values, which are not limited here. Among them, on the sequencing chip, the grids can be divided into row 1, row 2, row 3...row 100 from bottom to top according to the vertical direction of the reagent tank, that is, row n refers to row 100 at this time. The sequencing chip can be divided into grids, column 1, column 2, column 3, and so on, from left to right along the reagent tank. The preset algorithm can be an image analysis algorithm or another algorithm, without limitation. The preset brightness values can be, for example, 50 A.U., 55 A.U., 60 A.U., 65 A.U., 70 A.U., 75 A.U., 80 A.U., 85 A.U., 90 A.U., 95 A.U., and 100 A.U., without limitation.
[0135] Specifically, for example, after a sequencing chip undergoes nucleic acid sequencing in a reagent tank, the post-biochemical reaction sequencing chip can be transferred to an optomechanical device. The optomechanical device then photographs the post-biochemical reaction soaking reaction surface 231 of the sequencing chip, which is divided into 100 rows by 100 columns, to obtain 100 by 100 images, or 10,000 images. Then, the optomechanical device captures the 10,000 images of the post-biochemical reaction soaking reaction surface 231 of the sequencing chip, which is divided into 100 rows by 100 columns, in real time. The image brightness of the multiple images corresponding to the 100th row of images is calculated according to a preset algorithm. If the image brightness of the multiple images corresponding to the 100th row of images is lower than a preset brightness value, it indicates that the reagent level in the reagent tank is insufficient, resulting in an incomplete biochemical reaction on the sequencing chip. Automatic refilling of the reagent tank is then required.
[0136] In this way, the control method of the present application can obtain in real time multiple images corresponding to a preset number of rows and columns obtained by the optical-mechanical device taking pictures of the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction, and calculate the brightness of the multiple images according to a preset algorithm. If the brightness of the multiple images corresponding to the nth row on the sequencing chip, that is, the top row of the sequencing chip, which is divided from bottom to top in the vertical direction of the reagent tank, is lower than the preset brightness value, it is considered that the reagent liquid level in the reagent tank is insufficient, and the reagent tank is automatically replenished.
[0137] In certain embodiments, the fluid replacement strategy includes a fluid replacement strategy according to a second time interval. The control method includes:
[0138] 031: Taking the liquid addition time as the starting point, replace the liquid in the reagent tank according to the second time interval.
[0139] 2 , step 031 can be implemented by the execution module 12. The execution module 12 is configured to use the liquid addition time as a starting point and replace the liquid in the reagent tank according to the second time interval.
[0140] The second time interval may be, for example, 55 min, 56 min, 57 min, 58 min, 59 min, 60 min, 61 min, 62 min, 63 min, 64 min, and 62 min, which is not limited here.
[0141] That is, the present application can use the liquid addition time as the starting point to time the reagent tank in real time. When the time interval between the current time and the liquid addition time is the second time interval, the reagent tank is automatically replaced with liquid, and the reagent tank is subsequently automatically replaced with liquid at the second time interval.
[0142] It is understandable that if the reagents in the reagent tank are idle for a long time and are not used, the biochemical reaction effect will be reduced. Therefore, the present application can use the liquid addition time as the starting timing point and replace the liquid in the reagent tank according to the second time interval. This can avoid the problem that the biochemical reaction effect is reduced and the nucleic acid sequencing results are affected due to the reagents in the reagent tank being idle for a long time without being replaced.
[0143] In this way, the control method of the present application can use the liquid addition time as the starting timing point and replace the liquid in the reagent tank according to the second time interval, so that the user can set different liquid addition times according to different types of reagent tanks and automatically replace the liquid in the reagent tank.
[0144] Referring to FIG9 , in certain embodiments, the liquid replacement strategy includes a liquid replacement strategy based on the number of soaking reactions of the sequencing chip in the reagent tank. The control method includes:
[0145] 032: Determine in real time whether the number of immersion reactions is greater than or equal to a second threshold.
[0146] 041: When the number of immersion reactions is greater than or equal to the second threshold, the liquid in the reagent tank is replaced.
[0147] Referring to Figure 2 , step 032 can be implemented by determination module 11. Step 041 can be implemented by execution module 12. That is, determination module 11 is configured to determine in real time whether the number of immersion reactions is greater than or equal to a second threshold. Execution module 12 is configured to replace the reagent tank solution when the number of immersion reactions is greater than or equal to the second threshold.
[0148] Specifically, when nucleic acid sequencing begins, it can be determined in real time whether the number of immersion reactions of the sequencing chip in the time slot is greater than or equal to a second threshold, and when the number of immersion reactions is greater than or equal to the second threshold, the reagent slot is automatically replaced.
[0149] It should be noted that, due to the different viscosities of different reagents, the second threshold values set for different reagents will also vary, i.e., the greater the viscosity of the reagent, the smaller the second threshold value set. For example, as shown in FIG3 , reagent A1 and reagent A2 are placed in different reagent tanks, i.e., reagent A1 is placed in the first reagent tank 211 and reagent A2 is placed in the second reagent tank 212. The viscosity of reagent A1 is greater than that of reagent A2, so the second threshold value set for reagent A1 is smaller than the second threshold value set for reagent A2.
[0150] Understandably, when performing nucleic acid sequencing, the sequencing chip will soak and react in different reagent tanks according to biochemical requirements, stay for a certain period of time, and then be removed from the reagent tank and transferred to the next reagent tank. Due to the viscosity of the reagents and the surface tension of the liquid, the sequencing chip will carry some reagents from the previous reagent tank to the next reagent tank, contaminating the reagents in the next reagent tank and weakening the effect of the biochemical reaction. Therefore, the present application automatically replaces the reagent tank liquid when the number of soaking reactions is greater than or equal to the second threshold value to prevent the sequencing chip from carrying some reagents from the previous reagent tank to the next reagent tank, contaminating the reagents in the next reagent tank and weakening the effect of the biochemical reaction.
[0151] In this way, the control method of the present application can set different second thresholds according to reagents of different viscosities, and judge in real time whether the number of immersion reactions of the sequencing chip is greater than or equal to the second threshold, so as to automatically replace the liquid in the reagent tank when the number of immersion reactions is greater than or equal to the second threshold, thereby improving the efficiency of the reagent tank liquid replacement.
[0152] Referring to FIG. 10 , in certain embodiments, the liquid replacement strategy includes a liquid replacement strategy based on feedback from the imaging quality of the optical-mechanical device. The control method includes:
[0153] 033: Acquire multiple images corresponding to a preset number of rows and columns obtained by taking photos of the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical-mechanical device in real time.
[0154] 034: Calculate the brightness of multiple images according to the preset algorithm, and calculate the average brightness of the multiple images.
[0155] 042: If the average brightness value of the current round of images is less than the average brightness value of the previous round of images, the liquid in the reagent tank is replaced. In conjunction with Figure 2, steps 033 and 034 can be implemented by the judgment module 11. Step 042 can be implemented by the execution module 12. That is, the judgment module 11 is used to obtain in real time a plurality of images corresponding to a preset number of rows and a preset number of columns obtained by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical mechanical device; calculate the brightness of the plurality of images according to a preset algorithm, and calculate the brightness average value of the plurality of images. The execution module 12 is used to replace the liquid in the reagent tank if the average brightness value of the current round of images is less than the average brightness value of the previous round of images.
[0156] The preset algorithm may refer to an image analysis algorithm or other algorithms, which is not limited here.
[0157] The preset brightness values can be, for example, 50A.U., 55A.U., 60A.U., 65A.U., 70A.U., 75A.U., 80A.U., 85A.U., 90A.U., 95A.U. and 100A.U., without limitation here.
[0158] After the optical-mechanical device photographs the soaked reaction surface of the sequencing chip after the biochemical reaction is divided into a preset number of rows and a preset number of columns, a plurality of images having a preset number of rows and a preset number of columns can be obtained. For example, the number of rows and columns of the images obtained by the optical-mechanical device are both 100. The number of rows of the images is defined from bottom to top along the height direction within the reagent tank, with the lowest layer being row 1 and the top layer being row 100. Thus, 100 times 100 images can be obtained, or 10,000 images.
[0159] Specifically, after nucleic acid sequencing is performed on a sequencing chip within a reagent tank, the post-biochemical reaction sequencing chip can be transferred to an optomechanical device. The optomechanical device then photographs the post-biochemical reaction reaction surface of the sequencing chip, which is divided into 100 rows by 100 columns, to obtain 100 by 100 images, or 10,000 images. Then, the optomechanical device captures the 10,000 images of the post-biochemical reaction reaction surface of the sequencing chip, which is divided into 100 rows by 100 columns, in real time. The brightness of multiple images within a preset number of rows of images is calculated according to a preset algorithm, and the brightness average of the multiple images within the preset number of rows of images is calculated. If the average brightness of the current round of images is lower than the average brightness of the previous round of images, this indicates that the reagent reaction in the reagent tank is poor, and the reagent tank is automatically replaced.
[0160] In this way, the control method of the present application can obtain in real time multiple images corresponding to a preset number of rows and columns obtained by taking pictures of the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical-mechanical device, and after calculating the brightness of the multiple images according to the preset algorithm, calculate the brightness average of the multiple images. When the brightness average of the current round of images is less than the brightness average of the previous round of images, the reagent tank can be automatically replaced.
[0161] In addition, the present application can also calculate the brightness of multiple images according to a preset algorithm, and calculate the brightness average of multiple images. If the brightness average of the current round of images is less than a preset threshold, the reagent tank is automatically replaced. That is, after the sequencing chip performs nucleic acid sequencing in the reagent tank, the sequencing chip after the biochemical reaction can be transferred to the optical mechanical device, and the optical mechanical device is used to take pictures of the soaking reaction surface of the sequencing chip after the biochemical reaction divided into 100 rows and 100 columns to obtain 100 times 100 images, that is, 10,000 images. Then, 10,000 images are obtained in real time by the optical mechanical device on the soaking reaction surface of the sequencing chip after the biochemical reaction divided into 100 rows and 100 columns. At this time, the brightness of multiple images in the preset number of rows of images is calculated according to the preset algorithm, and the brightness average of multiple images in the preset number of rows of images is calculated. At this time, if the brightness average of the current round of images is less than the preset threshold, it means that the reagent reaction effect in the reagent tank is poor, and then the reagent tank is automatically replaced. It should be noted that the preset threshold value can be, for example, 10A.U., 20A.U., 30A.U., 40A.U., 50A.U., 60A.U., 70A.U., 80A.U., 90A.U. and 100A.U., and there is no limitation here.
[0162] Referring to FIG. 11 , in certain embodiments, the fluid replacement strategy includes a fluid replacement strategy according to different biochemical stages, and the control method includes:
[0163] 035: Determine the current sequencing stage of a nucleic acid sequencing workflow in real time.
[0164] 036: Determine whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent.
[0165] 043: When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the original liquid in the reagent tank is drained, and the target reagent is added to the reagent tank according to the target reagent volume.
[0166] Referring to Figure 2 , steps 035 and 036 can be implemented by determination module 11. Step 043 can be implemented by execution module 12. Specifically, determination module 11 is configured to determine the current sequencing stage of the nucleic acid sequencing process in real time and determine whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent. Execution module 12 is configured to drain the reagent tank of the original liquid and add the target reagent to the reagent tank according to the target reagent volume when the current sequencing stage reaches the target sequencing stage corresponding to the target reagent.
[0167] The sequencing stage may include a single-strand polymerase chain reaction sequencing stage and a double-strand polymerase chain reaction sequencing stage.
[0168] The target reagent may include reagent U or reagent G. The target sequencing stage corresponding to reagent U is the one-strand polymerase chain reaction sequencing stage, and the target sequencing stage corresponding to reagent G is the two-strand polymerase chain reaction sequencing stage.
[0169] The target reagent volume can be, for example, 28 mL, 29 mL, 30 mL, 31 mL, 32 mL, 33 mL, 34 mL, and 35 mL, which are not limited here.
[0170] For example, as shown in FIG3 , the target reagent is reagent G. When it is determined in real time that the current sequencing stage of the nucleic acid sequencing process is the two-strand polymerase chain reaction sequencing stage, and it is determined that the current sequencing stage has reached the two-strand polymerase chain reaction sequencing stage corresponding to reagent G, reagent U in the reagent tank 21 is emptied at this time, and reagent G is added to the reagent tank 21 according to the target reagent amount.
[0171] In this way, the control method of the present application determines the current sequencing stage of the nucleic acid sequencing process in real time, and judges whether the current sequencing stage has reached the target sequencing corresponding to the target reagent, so that when the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the original liquid in the reagent tank is emptied, and the target reagent is added to the reagent tank according to the target reagent volume. Then, according to the different sequencing stages of the nucleic acid sequencing process, the original liquid in the reagent tank can be automatically emptied, and the target reagent can be added to the reagent tank according to the target reagent volume to improve the reuse rate of the reagent tank.
[0172] The present application also provides a gene sequencer. The gene sequencer includes a control device 10 and a reagent tank. The control device 10 and the reagent tank in the embodiment of the present application are consistent with the description of the above embodiment and will not be repeated here.
[0173] In this way, the gene sequencer of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenishing liquid or replacing liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, addition or replacement of liquid in the reagent tank, thereby improving the efficiency of liquid replenishment, addition or replacement of liquid in the reagent tank.
[0174] The present application also provides a computer-readable storage medium storing a computer program, which, when executed by one or more processors, implements the control method in the above embodiment, which will not be described in detail here for the sake of brevity.
[0175] In this way, the computer-readable storage medium of the present application can determine in real time whether the trigger conditions corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank are met according to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, and add liquid, replenishing liquid or replacing liquid in the reagent tank when the trigger conditions are met, so as to realize automatic liquid replenishment, adding liquid or replacing liquid in the reagent tank, and improve the efficiency of liquid replenishment, adding liquid or replacing liquid in the reagent tank.
[0176] The above embodiments merely illustrate several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.
Claims
1. A control method, It is characterized in that The control method comprises: According to the preset liquid adding strategy, liquid replenishing strategy or liquid changing strategy, it is judged in real time whether the triggering conditions corresponding to liquid adding, liquid replenishing or liquid changing of the reagent tank are met; When the trigger condition is reached, the reagent tank is filled with liquid, supplemented with liquid or replaced with liquid.
2. The control method according to claim 1, It is characterized in that The liquid addition strategy includes a strategy for adding different target reagents and target reagent amounts to the reagent tank according to different sequencing stages of the nucleic acid sequencing process; The control method comprises: determining in real time the current sequencing stage of the nucleic acid sequencing process; Determining whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent; and, When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, the target reagent is added to the reagent tank according to the target reagent amount.
3. The control method according to claim 1, It is characterized in that The rehydration strategy includes a strategy of rehydrating according to a first time interval, and the rehydrating of the reagent tank when the trigger condition is met includes: The liquid addition time is used as the starting timing point, and the reagent tank is replenished with liquid according to the first time interval.
4. The control method according to claim 3, It is characterized in that The step of replenishing the reagent tank with liquid when the trigger condition is reached also includes: The last time of replenishing liquid is used as the starting time point, and the reagent tank is replenished with liquid according to the first time interval.
5. The control method according to claim 1, It is characterized in that The rehydration strategy includes a strategy of rehydrating according to the number of immersion reactions of the sequencing chip in the reagent tank; the control method includes: Determine in real time whether the soaking reaction number is greater than or equal to a first threshold; When the number of immersion reactions is greater than or equal to the first threshold, the reagent tank is replenished with liquid.
6. The control method according to claim 1, It is characterized in that The fluid replenishment strategy includes a strategy of performing fluid replenishment according to an electrical signal fed back by a liquid level sensor, wherein the liquid level sensor is disposed on a hose outside the reagent tank and connected to the reagent tank, and the control method includes: Acquire the electrical signal output by the liquid level sensor in real time; The reagent reservoir is replenished with liquid according to the electrical signal.
7. The control method according to claim 1, It is characterized in that The fluid replenishment strategy includes a strategy for replenishing fluid according to feedback results of the photographing quality of the optical mechanical device, and the control method includes: Acquire in real time a plurality of images corresponding to a preset number of rows and a preset number of columns obtained by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical-mechanical device; the plurality of images corresponding to the preset number of rows are a plurality of images corresponding to grids divided from the 1st row to the nth row from bottom to top along the vertical direction of the reagent tank on the sequencing chip, where n is greater than 1; Calculating the brightness of the multiple images according to a preset algorithm; If the brightness of the multiple images corresponding to the nth row is lower than a preset brightness value, the reagent tank is replenished with liquid.
8. The control method according to claim 1, It is characterized in that The fluid replacement strategy includes a strategy for performing fluid replacement according to a second time interval, and the control method includes: The liquid addition time is used as the starting point for timing, and the liquid in the reagent tank is replaced according to the second time interval.
9. The control method according to claim 1, It is characterized in that The liquid replacement strategy includes a strategy for performing liquid replacement according to the number of immersion reactions of the sequencing chip in the reagent tank, and the control method includes: Determine in real time whether the soaking reaction number is greater than or equal to a second threshold; When the number of immersion reactions is greater than or equal to the second threshold, the liquid in the reagent tank is replaced.
10. The control method according to claim 1, It is characterized in that The liquid replacement strategy includes a liquid replacement strategy based on feedback results of the photographing quality of the optical-mechanical device, and the control method includes: Acquire in real time a plurality of images corresponding to a preset number of rows and a preset number of columns obtained by photographing the immersion reaction surface of the sequencing chip removed from the reagent tank after the biochemical reaction by the optical-mechanical device; Calculating the brightness of the multiple images according to a preset algorithm, and calculating the brightness average of the multiple images; If the average brightness of the current round of images is less than the average brightness of the previous round of images, the liquid in the reagent tank is replaced.
11. The control method according to claim 1, It is characterized in that The fluid replacement strategy includes a strategy for performing fluid replacement according to different biochemical stages, and the control method includes: Determine the current sequencing stage of the nucleic acid sequencing process in real time; Determining whether the current sequencing stage has reached the target sequencing stage corresponding to the target reagent; When the current sequencing stage reaches the target sequencing stage corresponding to the target reagent, The original liquid in the reagent tank is drained, and the target reagent is added into the reagent tank according to the target reagent amount.
12. A gene sequencer, It is characterized in that The gene sequencer comprises a control device and a reagent tank, wherein the control device comprises: A judgment module, used to judge in real time whether a trigger condition corresponding to adding liquid, replenishing liquid or replacing liquid in the reagent tank is met according to a preset liquid adding strategy, liquid replenishing strategy or liquid replacing strategy; The execution module is used to add liquid, replenish liquid or replace liquid in the reagent tank when the trigger condition is met.
13. A computer-readable storage medium, It is characterized in that The computer-readable storage medium stores a computer program, and when the computer program is executed by one or more processors, the control method according to any one of claims 1 to 11 is implemented.
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