Oligo synthesizer liquid calibration method, device, electronic device and storage medium

Abstract

The present application provides an oligo synthesizer calibration method, device, electronic device and storage medium, which use a trace liquid measuring instrument to replace the traditional manual calibration of the oligo synthesizer liquid injection accuracy, solve the problem of unstable production batch quality caused by the inconsistent accuracy of different synthesizers, and avoid the phenomenon that the synthesizer calibration depends on specific personnel, thereby realizing the automation and standardization of the oligo synthesizer calibration.

Description

Technical Field

[0001] The present invention relates to the technical field of Oligo synthesizers, and in particular to a method, device, electronic equipment and storage medium for calibrating a liquid of an Oligo synthesizer. Background Art

[0002] Oligo synthesizer is an instrument for automatically synthesizing short-fragment oligonucleotides. It is mainly used in the field of DNA and RNA synthesis. It is one of the indispensable and most widely used equipment in the synthesis field.

[0003] The synthesis quality of Oligo synthesizers on the market varies greatly. The synthesis quality of different equipment varies. The reason is that Oligo synthesizers need to be calibrated by professionals before use, that is, to calibrate the accuracy of the amount of reagents dispensed each time. The amount of liquid used for normal synthesis is between 5 microliters and 10 milliliters, and the synthesis quality can be guaranteed within a deviation of 5%. However, there is currently no unified method and equipment for standardized operation in terms of liquid volume calibration. Manual calibration is used entirely, and the calibration results of different personnel depend entirely on experience accumulation. Summary of the invention

[0004] The present invention provides an Oligo synthesizer liquid calibration method, device, electronic equipment and storage medium, which are used to replace manual calibration of the Oligo synthesizer liquid injection accuracy, and realize the automation and standardization of the Oligo synthesizer liquid calibration.

[0005] In a first aspect, the present invention provides a method for calibrating an oligo synthesizer, comprising:

[0006] In response to a calibration request, a capillary in a micro-liquid measuring instrument is inserted into the bottom of the test agent; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom;

[0007] The motor is used to rotate and lift the plunger, thereby driving the capillary tube to absorb liquid;

[0008] When the photoelectric sensor measures that there is air in the capillary tube, the rotation operation of the motor is stopped, and the real-time motor angle and the length from the liquid surface to the bottom of the capillary tube are determined;

[0009] Calculating the measured volume of the test agent based on the real-time motor angle;

[0010] Determining a measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer information;

[0011] Based on the measurement error, adjusting the measured volume of the test agent to obtain an actual reagent volume;

[0012] The steel needle dispensing performance of the Oligo synthesizer is determined based on the actual reagent volume and the dispensing amount of the test reagent by the Oligo synthesizer.

[0013] Optionally, the measurement error includes: an error in the capillary, a moving distance error and a resolution error; the synthesizer information includes: synthesizer attribute information and synthesizer operation information; the synthesizer attribute information includes: 4-fold frequency minimum resolution, capillary diameter, plunger diameter and measurement accuracy error distance; the synthesizer operation information includes: the response time of the photoelectric sensor, the motor speed and the motor acceleration and deceleration time; based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer attribute information, determining the measurement error includes:

[0014] The air volume below the capillary is determined by using a preset expression for determining the air volume below the capillary, combining the length from the liquid surface to the bottom of the capillary and the diameter of the capillary; the air volume below the capillary is the error inside the capillary;

[0015] Determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter;

[0016] The resolution error is determined by using a preset expression for determining the resolution error, combining the 4-fold frequency minimum resolution and the plunger diameter.

[0017] Optionally, adjusting the measured volume of the test agent based on the measurement error to obtain the actual reagent volume includes:

[0018] Determining a total measurement error based on the capillary internal error, the moving distance error, and the resolution error;

[0019] The measured volume of the test reagent is adjusted according to the total measurement error to obtain a first actual reagent volume whose value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose value is the difference between the measured volume and the total measurement error.

[0020] Optionally, the steel needle dispensing performance of the Oligo synthesizer is determined based on the actual reagent volume and the dispensing amount of the test agent by the Oligo synthesizer, including:

[0021] Determining whether the amount of the test reagent dispensed by the Oligo synthesizer is within the interval formed by the first actual reagent volume or the second actual reagent volume;

[0022] If yes, it is defined that the needle allocation performance meets the requirements;

[0023] If not, adjust and correct the allocated amount;

[0024] Optionally, the air volume at the bottom of the capillary is determined by:

[0025] V 空 =(D1 / 2) 2 *π*L;

[0026] The moving distance error determination expression is:

[0027] E 电 =(T1+T2)*S2*π*(D2 / 2) 2 ;

[0028] The resolution error determination expression is:

[0029] E 辨 =π*(D2 / 2) 2 *1 / F;

[0030] Among them, V 空 is the air volume under the capillary, D1 is the capillary diameter, L is the measurement accuracy error distance under the visual measurement method, E 电 is the moving distance error, T1 is the response time of the photoelectric sensor, S2 is the motor speed, T2 is the motor acceleration and deceleration time, E 辨 is the resolution error, and F is the minimum resolution of 4 times the frequency.

[0031] In a second aspect, the present invention provides an Oligo synthesizer liquid calibration device, comprising:

[0032] A response module is used to insert a capillary in a micro-liquid measuring instrument into the bottom of the test agent in response to a calibration request; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom;

[0033] A liquid aspiration module, used for driving the capillary to aspirate liquid by rotating the lifting plunger through the motor;

[0034] A length determination module, used to stop the rotation operation of the motor and determine the real-time motor angle and the length from the liquid surface to the bottom of the capillary tube when the photoelectric sensor measures the presence of air in the capillary tube;

[0035] A volume measurement module, used for calculating the measurement volume of the test agent based on the real-time motor angle;

[0036] an error determination module, for determining a measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer information;

[0037] An adjustment module, used for adjusting the measured volume of the reagent to be tested based on the measurement error to obtain an actual reagent volume;

[0038] The liquid calibration module is used to determine the steel needle distribution performance of the Oligo synthesizer based on the actual reagent volume and the distribution amount of the Oligo synthesizer for the test reagent.

[0039] Optionally, the measurement error includes: an error in the capillary, a moving distance error and a resolution error; the synthesizer information includes: synthesizer attribute information and synthesizer operation information; the synthesizer attribute information includes: 4 times the minimum resolution, capillary diameter, plunger diameter and measurement accuracy error distance; the synthesizer operation information includes: the response time of the photoelectric sensor, the motor speed and the motor acceleration and deceleration time; the error determination module includes:

[0040] The capillary internal error determination submodule is used to determine the capillary lower air volume by using a preset capillary lower air volume determination expression, combining the length from the capillary liquid surface to the bottom, and the capillary diameter; the capillary lower air volume is the capillary internal error;

[0041] A moving distance error determination submodule, used to determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter;

[0042] The resolution error determination submodule is used to determine the resolution error by using a preset resolution error determination expression in combination with the 4-fold frequency minimum resolution and the plunger diameter.

[0043] Optionally, the adjustment module includes:

[0044] A total error determination submodule, used to determine a total measurement error based on the capillary error, the moving distance error and the resolution error;

[0045] The adjustment submodule is used to adjust the measured volume of the test agent based on the total measurement error to obtain a first actual reagent volume whose numerical value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose numerical value is the difference between the measured volume and the total measurement error.

[0046] In a third aspect, the present invention provides an electronic device, comprising a processor and a memory, wherein the memory stores computer-readable instructions, and when the computer-readable instructions are executed by the processor, the steps in the method provided in the first aspect are performed.

[0047] In a fourth aspect, the present invention provides a storage medium having a computer program stored thereon, wherein the computer program, when executed by a processor, runs the steps of the method provided in the first aspect.

[0048] It can be seen from the above technical solutions that the present invention has the following advantages:

[0049] The invention provides a method, device, electronic device and storage medium for calibrating liquid of an Oligo synthesizer. The method comprises: in response to a calibration request, inserting a capillary in a trace liquid measuring instrument into the bottom of a test agent; the trace liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom; the motor rotates and lifts the plunger to drive the capillary to absorb liquid; when the photoelectric sensor measures that there is air in the capillary, the rotation operation of the motor is stopped, and the real-time motor angle and the length from the liquid surface of the capillary to the bottom are determined; based on the real-time motor angle, the measured volume of the test agent is calculated; based on the real-time motor angle and the length from the liquid surface of the capillary to the bottom, and the synthesizer information obtained, the measurement error is determined; based on the measurement error, the measured volume of the test agent is adjusted to obtain the actual reagent volume; based on the actual reagent volume and the distribution amount of the Oligo synthesizer for the test agent, the steel needle distribution performance of the Oligo synthesizer is determined. By using a micro-liquid measuring instrument to replace the traditional manual calibration of the Oligo synthesizer's liquid injection accuracy, we can solve the problem of unstable production batch quality caused by the inconsistent accuracy of different synthesizers, avoid the phenomenon that the synthesizer calibration depends on specific personnel, and thus realize the automation and standardization of Oligo synthesizer calibration. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. 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 paying creative labor.

[0051] Figure 1 A flow chart of the steps of Example 1 of a method for calibrating a liquid in an Oligo synthesizer according to the present invention;

[0052] Figure 2A flow chart of the steps of Example 2 of a method for calibrating a solution of an Oligo synthesizer according to the present invention;

[0053] Figure 3 The present invention is a structural block diagram of an embodiment of a liquid calibration device for an Oligo synthesizer. DETAILED DESCRIPTION

[0054] The embodiment of the present invention provides an Oligo synthesizer liquid calibration method, device, electronic equipment and storage medium, which are used to replace manual calibration of the Oligo synthesizer liquid injection accuracy, and realize the automation and standardization of the Oligo synthesizer liquid calibration.

[0055] In order to make the purpose, features and advantages of the present invention more obvious and easy to understand, 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 below 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 creative work are within the scope of protection of the present invention.

[0056] Embodiment 1

[0057] See also Figure 1 , Figure 1 The present invention is a process step diagram of a first embodiment of a method for calibrating a liquid in an Oligo synthesizer, the method comprising:

[0058] Step S1, in response to a calibration request, inserting a capillary in a micro-liquid measuring instrument into the bottom of a test sample; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom;

[0059] The purpose of the Oligo synthesizer calibration is to ensure that the concentration and volume of reagents used in the synthesis reaction, such as amino acids and nucleotides, are precisely controlled to ensure the quality and stability of the synthetic products.

[0060] Step S2, rotating the lifting plunger by the motor to drive the capillary to absorb liquid;

[0061] In the embodiment of the present invention, the motor rotates to lift the plunger, causing the plunger to move up and down, thereby changing the pressure in the capillary tube to achieve the operation of aspirating or discharging liquid. This design can achieve precise control and regulation of the amount of liquid aspirated.

[0062] Step S3, when the photoelectric sensor measures that there is air in the capillary tube, the rotation operation of the motor is stopped, and a real-time motor angle and a length from the liquid surface to the bottom of the capillary tube are determined;

[0063] In the embodiment of the present invention, by stopping the motor rotation when bubbles are detected, it is possible to avoid sucking bubbles into the system to cause adverse effects. At the same time, by determining the real-time motor angle and the length from the capillary liquid surface to the bottom, real-time monitoring and adjustment of the operating state can be achieved to ensure the accuracy and stability of the liquid suction operation.

[0064] Step S4, calculating the measurement volume of the test agent based on the real-time motor angle;

[0065] In the embodiment of the present invention, a mapping relationship between the motor angle and the liquid volume can be established through preliminary experiments or simulations, that is, the liquid volume corresponding to each specific motor angle. Therefore, in practical applications, after determining the real-time motor angle, the measured volume of the test agent can be calculated based on the recorded real-time motor angle and the corresponding mapping relationship.

[0066] Step S5, determining a measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer information;

[0067] Step S6, adjusting the measured volume of the test reagent based on the measurement error to obtain an actual reagent volume;

[0068] Step S7, determining the needle dispensing performance of the Oligo synthesizer based on the actual reagent volume and the dispensing amount of the test reagent by the Oligo synthesizer.

[0069] In the embodiment of the present invention, by comparing the reagent volume actually dispensed by the Oligo synthesizer needle with the dispensing amount set by the Oligo synthesizer, the accuracy and reliability of the needle can be determined. If the actual reagent volume deviates greatly from the set dispensing amount, it indicates that there may be a problem with the dispensing performance of the Oligo synthesizer needle, and further adjustment or maintenance is required.

[0070] An Oligo synthesizer calibration method provided by an embodiment of the present invention comprises: in response to a calibration request, inserting a capillary in a trace liquid measuring instrument into the bottom of a test agent; the trace liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom; the motor rotates and lifts the plunger to drive the capillary to absorb liquid; when the photoelectric sensor measures that there is air in the capillary, the rotation operation of the motor is stopped, and the real-time motor angle and the length from the capillary liquid surface to the bottom are determined; based on the real-time motor angle, the measured volume of the test agent is calculated; based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the synthesizer information obtained, the measurement error is determined; based on the measurement error, the measured volume of the test agent is adjusted to obtain the actual reagent volume; based on the actual reagent volume and the distribution amount of the Oligo synthesizer for the test agent, the steel needle distribution performance of the Oligo synthesizer is determined. By using a micro-liquid measuring instrument to replace the traditional manual calibration of the Oligo synthesizer's liquid injection accuracy, we can solve the problem of unstable production batch quality caused by the inconsistent accuracy of different synthesizers, avoid the phenomenon that the synthesizer calibration depends on specific personnel, and thus realize the automation and standardization of Oligo synthesizer calibration.

[0071] Embodiment 2

[0072] See also Figure 2 , Figure 2 This is a flow chart of Example 2 of a method for calibrating a liquid in an Oligo synthesizer according to the present invention, the steps comprising:

[0073] S201, in response to a calibration request, inserting a capillary in a micro-liquid measuring instrument into the bottom of the test agent; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom;

[0074] S202, rotating the lifting plunger by the motor to drive the capillary to absorb liquid;

[0075] S203, when the photoelectric sensor measures that there is air in the capillary tube, stopping the rotation operation of the motor, and determining a real-time motor angle and a length from the liquid surface to the bottom of the capillary tube;

[0076] S204, calculating the measurement volume of the test agent based on the real-time motor angle;

[0077] S205, determining a measurement error based on the real-time motor angle, the length from the capillary liquid surface to the bottom, and the acquired synthesizer information;

[0078] In an optional embodiment, the measurement error includes: an error in the capillary, a moving distance error and a resolution error; the synthesizer information includes: synthesizer attribute information and synthesizer operation information; the synthesizer attribute information includes: 4 times the minimum resolution, capillary diameter, plunger diameter and measurement accuracy error distance; the synthesizer operation information includes: the response time of the photoelectric sensor, the motor speed and the motor acceleration and deceleration time; based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer attribute information, the measurement error is determined, including:

[0079] The air volume below the capillary is determined by using a preset expression for determining the air volume below the capillary, combining the length from the liquid surface to the bottom of the capillary and the diameter of the capillary; the air volume below the capillary is the error inside the capillary;

[0080] Determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter;

[0081] The resolution error is determined by using a preset expression for determining the resolution error, combining the 4-fold frequency minimum resolution and the plunger diameter.

[0082] Specifically, the expression for determining the volume of air in the lower part of the capillary is:

[0083] V 空 =(D1 / 2) 2 *π*L;

[0084] The moving distance error determination expression is:

[0085] E 电 =(T1+T2)*S2*π*(D2 / 2) 2 ;

[0086] The resolution error determination expression is:

[0087] E 辨 =π*(D2 / 2) 2 *1 / F;

[0088] Among them, V 空 is the air volume under the capillary, D1 is the capillary diameter, L is the measurement accuracy error distance under the visual measurement method, E 电 is the moving distance error, T1 is the response time of the photoelectric sensor, S2 is the motor speed, T2 is the motor acceleration and deceleration time, E 辨 is the resolution error, and F is the minimum resolution of 4 times the frequency.

[0089] In the embodiment of the present invention, the micro-liquid measuring instrument of the present invention adopts a plunger with a maximum capacity of 7.8ml, an inner diameter of 10mm and a length of 100mm. The plunger is pulled by a lead screw and a motor with a lead of 1mm. The motor is equipped with a 2500-line encoder, and the minimum resolution of 4 times the frequency is 4*2500=10000. The motor angle detection accuracy is (360 / 10000)°, and the corresponding lead screw movement distance is 1 / 10000mm. Based on these data, substituting them into the pre-set resolution error determination expression, the resolution error (liquid volume) can be obtained as: 1 / 10000mm*π(10 / 2) 2 ≈7.85nl, that is, the resolution error of the piston part of this device is 7.85nl.

[0090] At the same time, the plunger liquid inlet uses a capillary as the liquid suction head. There is a high-precision photoelectric sensor on the capillary. When there is no liquid in the capillary, a switch signal is transmitted to the controller. The capillary diameter is selected to be 0.5mm. The length of the capillary below the position detected by the sensor signal is fixed and can be measured by measurement. The visual measurement method is used here with a measurement accuracy of 1 micron. Based on the measurement accuracy error distance under the visual measurement method, the error in the capillary is converted to the volume of the capillary under a length of 1 micron. Combined with the pre-set expression for the air volume at the bottom of the capillary, the air volume at the bottom of the capillary is obtained as: (0.5mm / 2) 2 *π*1*10 -3 ≈0.62nl.

[0091] In addition, the response speed of the sensor is generally 15us, the motor acceleration and deceleration is set to 1ms, and the motor speed is generally 1 revolution per second. Substituting the preset moving distance error determination expression, the moving distance error can be obtained as follows: (0.001S+0.000015S)*1mm / s*π(10mm / 2) 2 ≈78.5nl.

[0092] S206, determining a total measurement error based on the capillary internal error, the moving distance error, and the resolution error;

[0093] In the embodiment of the present invention, the total measurement error is the sum of the error in the capillary, the moving distance error and the resolution error, that is, the total measurement error=0.62nl+78.5nl+7.85nl=86.97nl.

[0094] Therefore, the measurement error of the micro-volume measuring instrument in the embodiment of the present invention is ±86.97 nl.

[0095] S207, adjusting the measured volume of the test reagent according to the total measurement error to obtain a first actual reagent volume whose numerical value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose numerical value is the difference between the measured volume and the total measurement error;

[0096] In an embodiment of the present invention, the capillary is inserted into the bottom of the reagent to be measured, the motor position information is cleared, and the motor is started to drive the screw rod in the plunger to rise, so that all the measured reagents are completely pumped out through the capillary. When the reagent is emptied, air will appear in the capillary. At this time, the photoelectric sensor detects a light reflection change signal, which prompts the motor to stop running. At this time, the number of rotations of the motor is read. The distance moved by the plunger is converted by the screw rod lead, and the liquid volume is calculated according to the cross-sectional area of ​​the plunger. The volume at this time includes the air volume of the lower half of the capillary from the sensor position, that is, the volume in the capillary, and the movement distance error of the plunger in the time difference when the sensor detects that the motor stops. The actual reagent volume is obtained by removing the volume in the capillary, the movement distance error and the resolution error.

[0097] S208, determining whether the distribution amount of the test reagent by the Oligo synthesizer is within the interval formed by the first actual reagent volume or the second actual reagent volume; if so, defining the steel needle distribution performance as meeting the requirements; if not, adjusting and correcting the distribution amount.

[0098] The embodiment of the present invention discloses a method for calibrating liquid of an Oligo synthesizer, comprising: in response to a calibration request, inserting a capillary in a micro-liquid measuring instrument into the bottom of a test agent; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom; the motor rotates and lifts the plunger to drive the capillary to absorb liquid; when the photoelectric sensor measures that there is air in the capillary, the rotation operation of the motor is stopped, and the real-time motor angle and the length from the liquid surface of the capillary to the bottom are determined; based on the real-time motor angle, the measured volume of the test agent is calculated; based on the real-time motor angle and the length from the liquid surface of the capillary to the bottom, and the synthesizer information obtained, the measurement error is determined; based on the measurement error, the measured volume of the test agent is adjusted to obtain the actual reagent volume; based on the actual reagent volume and the distribution amount of the Oligo synthesizer for the test agent, the steel needle distribution performance of the Oligo synthesizer is determined. By using a micro-liquid measuring instrument to replace the traditional manual calibration of the Oligo synthesizer's liquid injection accuracy, we can solve the problem of unstable production batch quality caused by the inconsistent accuracy of different synthesizers, avoid the phenomenon that the synthesizer calibration depends on specific personnel, and thus realize the automation and standardization of Oligo synthesizer calibration.

[0099] Embodiment 3

[0100] See also Figure 3 , Figure 3 This is a structural block diagram of an embodiment of an Oligo synthesizer liquid calibration device of the present invention, the device comprises:

[0101] The response module 301 is used to respond to the calibration request and insert the capillary in the micro-liquid measuring instrument into the bottom of the test agent; the micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom;

[0102] The liquid aspiration module 302 is used to drive the capillary to aspirate liquid by rotating the lifting plunger through the motor;

[0103] The length determination module 303 is used to stop the rotation operation of the motor and determine the real-time motor angle and the length from the liquid surface to the bottom of the capillary tube when the photoelectric sensor measures the presence of air in the capillary tube;

[0104] A volume measurement module 304, used to calculate the measurement volume of the test agent based on the real-time motor angle;

[0105] An error determination module 305 is used to determine a measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer information;

[0106] An adjustment module 306, configured to adjust the measured volume of the test agent based on the measurement error to obtain an actual reagent volume;

[0107] The liquid calibration module 307 is used to determine the needle dispensing performance of the Oligo synthesizer based on the actual reagent volume and the dispensing amount of the test reagent by the Oligo synthesizer.

[0108] In an optional embodiment, the measurement error includes: error in the capillary, movement distance error and resolution error; the synthesizer information includes: synthesizer attribute information and synthesizer operation information; the synthesizer attribute information includes: 4 times frequency minimum resolution, capillary diameter, plunger diameter and measurement accuracy error distance; the synthesizer operation information includes: response time of the photoelectric sensor, motor speed and motor acceleration and deceleration time; the error determination module 305 includes:

[0109] The capillary internal error determination submodule is used to determine the capillary lower air volume by using a preset capillary lower air volume determination expression, combining the length from the capillary liquid surface to the bottom, and the capillary diameter; the capillary lower air volume is the capillary internal error;

[0110] A moving distance error determination submodule, used to determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter;

[0111] The resolution error determination submodule is used to determine the resolution error by using a preset resolution error determination expression in combination with the 4-fold frequency minimum resolution and the plunger diameter.

[0112] In an optional embodiment, the adjustment module 306 includes:

[0113] A total error determination submodule, used to determine a total measurement error based on the capillary error, the moving distance error and the resolution error;

[0114] The adjustment submodule is used to adjust the measured volume of the test agent based on the total measurement error to obtain a first actual reagent volume whose numerical value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose numerical value is the difference between the measured volume and the total measurement error.

[0115] In an optional embodiment, the liquid calibration module 307 includes:

[0116] A judgment submodule, used for judging whether the amount of the test reagent distributed by the Oligo synthesizer is within the interval formed by the first actual reagent volume or the second actual reagent volume;

[0117] If yes, it is defined that the needle allocation performance meets the requirements;

[0118] If not, the allocated amount is adjusted and corrected.

[0119] In an optional embodiment, the volume of air in the lower part of the capillary is determined by the expression:

[0120] V 空 =(D1 / 2) 2 *π*L;

[0121] The moving distance error determination expression is:

[0122] E 电 =(T1+T2)*S2*π*(D2 / 2) 2 ;

[0123] The resolution error determination expression is:

[0124] E 辨 =π*(D2 / 2) 2 *1 / F;

[0125] Among them, V 空 is the air volume at the bottom of the capillary, D1 is the capillary diameter, L is the length from the capillary liquid surface to the bottom, E 电 is the moving distance error, T1 is the response time of the photoelectric sensor, S2 is the motor speed, T2 is the motor acceleration and deceleration time, E 辨 is the resolution error, and F is the minimum resolution of 4 times the frequency.

[0126] Embodiment 4

[0127] An embodiment of the present invention further provides an electronic device, including a memory and a processor, wherein the memory stores a computer program, and when the computer program is executed by the processor, the processor executes the steps of an Oligo synthesizer calibration method of any embodiment.

[0128] Embodiment 5

[0129] An embodiment of the present invention further provides a computer storage medium having a computer program stored thereon, and when the computer program is executed by the processor, the steps of a method for calibrating a liquid of an Oligo synthesizer of any embodiment are implemented.

[0130] Those skilled in the art can clearly understand that, for the convenience and brevity of description, the specific working processes of the systems, devices and units described above can refer to the corresponding processes in the aforementioned method embodiments and will not be repeated here.

[0131] In the several embodiments provided in the present application, it should be understood that the methods, devices, electronic devices and storage media disclosed in the present invention can be implemented in other ways. For example, the device embodiments described above are only schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some interfaces, indirect coupling or communication connection of devices or units, which can be electrical, mechanical or other forms.

[0132] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0133] In addition, each functional unit in each embodiment of the present invention may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit. The above-mentioned integrated unit may be implemented in the form of hardware or in the form of software functional units.

[0134] If the integrated unit is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention is essentially or the part that contributes to the prior art or all or part of the technical solution can be embodied in the form of a software product. The computer software product is stored in a readable storage medium, including several instructions for a computer device (which can be a personal computer, a server, or a network device, etc.) to perform all or part of the steps of the method described in each embodiment of the present invention. The aforementioned readable storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk and other media that can store program codes.

[0135] As described above, the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features thereof may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for calibrating an oligo synthesizer, characterized in that: include: In response to a calibration request, inserting a capillary in the microfluid measuring instrument into the bottom of the test agent; The micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom; The motor is used to rotate and lift the plunger, thereby driving the capillary tube to absorb liquid; When the photoelectric sensor measures that there is air in the capillary tube, the rotation operation of the motor is stopped, and the real-time motor angle and the length from the liquid surface to the bottom of the capillary tube are determined; Calculating the measured volume of the test agent based on the real-time motor angle; Based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the synthesizer information obtained, the measurement error is determined; the measurement error includes: error in the capillary, movement distance error and resolution error; the synthesizer information includes: synthesizer attribute information and synthesizer operation information; the synthesizer attribute information includes: 4 times frequency minimum resolution, capillary diameter, plunger diameter and measurement accuracy error distance; the synthesizer operation information includes: response time of the photoelectric sensor, motor speed and motor acceleration and deceleration time; Based on the measurement error, adjusting the measured volume of the test agent to obtain an actual reagent volume; Determining the needle dispensing performance of the Oligo synthesizer based on the actual reagent volume and the dispensing amount of the test reagent by the Oligo synthesizer; Determining a measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the acquired synthesizer property information, includes: The air volume below the capillary is determined by using a preset expression for determining the air volume below the capillary, combining the length from the liquid surface to the bottom of the capillary and the diameter of the capillary; the air volume below the capillary is the error inside the capillary; Determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter; The resolution error is determined by using a preset expression for determining the resolution error, in combination with the 4-fold frequency minimum resolution and the plunger diameter.

2. The method for calibrating the liquid of an Oligo synthesizer according to claim 1, characterized in that: Based on the measurement error, adjusting the measured volume of the reagent to be tested to obtain the actual reagent volume includes: Determining a total measurement error based on the capillary internal error, the moving distance error, and the resolution error; The measured volume of the test reagent is adjusted according to the total measurement error to obtain a first actual reagent volume whose value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose value is the difference between the measured volume and the total measurement error.

3. The method for calibrating the liquid of an Oligo synthesizer according to claim 2, characterized in that: Based on the actual reagent volume and the distribution amount of the test reagent by the Oligo synthesizer, the steel needle distribution performance of the Oligo synthesizer is determined, including: Determining whether the amount of the test reagent dispensed by the Oligo synthesizer is within the interval formed by the first actual reagent volume or the second actual reagent volume; If yes, it is defined that the needle allocation performance meets the requirements; If not, the allocated amount is adjusted and corrected.

4. The method for calibrating the liquid of an Oligo synthesizer according to claim 1, characterized in that: The expression for determining the volume of air at the bottom of the capillary is: V 空 =(D1 / 2) 2 *π*L; The moving distance error determination expression is: <h2 style=";text-align:left;direction:ltr">E<h2 style=";text-align:left;direction:ltr"> 电 <h2 style=";text-align:left;direction:ltr"> (T1+T2)*S2*π*(D2 / 2)<h2 style=";text-align:left;direction:ltr"> 2 <h2 style=";text-align:left;direction:ltr"> ; The resolution error determination expression is: E 辨 =π*(D2 / 2) 2 *1 / F; Among them, V 空 is the air volume under the capillary, D1 is the capillary diameter, L is the measurement accuracy error distance under the visual measurement method, E 电 is the moving distance error, T1 is the response time of the photoelectric sensor, S2 is the motor speed, T2 is the motor acceleration and deceleration time, E 辨 is the resolution error, and F is the minimum resolution of 4 times the frequency.

5. An oligo synthesizer liquid calibration device, characterized in that: include: A response module, for inserting a capillary in the micro-liquid measuring instrument into the bottom of the test agent in response to a calibration request; The micro-liquid measuring instrument is composed of a photoelectric sensor and a screw part, and the screw part is respectively equipped with a motor, a plunger and the capillary from top to bottom; A liquid aspiration module, used for driving the capillary to aspirate liquid by rotating the lifting plunger through the motor; A length determination module, used to stop the rotation operation of the motor and determine the real-time motor angle and the length from the liquid surface to the bottom of the capillary tube when the photoelectric sensor measures the presence of air in the capillary tube; A volume measurement module, used for calculating the measurement volume of the test agent based on the real-time motor angle; The error determination module is used to determine the measurement error based on the real-time motor angle and the length from the capillary liquid surface to the bottom, and the synthesizer information obtained; the measurement error includes: the error in the capillary, the moving distance error and the resolution error; the synthesizer information includes: the synthesizer attribute information and the synthesizer operation information; the synthesizer attribute information includes: the minimum resolution of 4 times the frequency, the capillary diameter, the plunger diameter and the measurement accuracy error distance; the synthesizer operation information includes: the response time of the photoelectric sensor, the motor speed and the motor acceleration and deceleration time; An adjustment module, used for adjusting the measured volume of the test agent based on the measurement error to obtain an actual reagent volume; A liquid calibration module, used to determine the needle dispensing performance of the Oligo synthesizer based on the actual reagent volume and the dispensing amount of the Oligo synthesizer for the test reagent; The error determination module comprises: The capillary internal error determination submodule is used to determine the capillary lower air volume by using a preset capillary lower air volume determination expression, combining the length from the capillary liquid surface to the bottom, and the capillary diameter; the capillary lower air volume is the capillary internal error; A moving distance error determination submodule, used to determine the moving distance error by using a preset moving distance error determination expression in combination with the response time, the motor speed, the motor acceleration / deceleration time and the plunger diameter; The resolution error determination submodule is used to determine the resolution error by using a preset resolution error determination expression in combination with the 4-fold frequency minimum resolution and the plunger diameter.

6. The Oligo synthesizer liquid calibration device according to claim 5, characterized in that: The adjustment module comprises: A total error determination submodule, used to determine a total measurement error based on the capillary error, the moving distance error and the resolution error; The adjustment submodule is used to adjust the measured volume of the test agent based on the total measurement error to obtain a first actual reagent volume whose numerical value is the sum of the measured volume and the total measurement error, and a second actual reagent volume whose numerical value is the difference between the measured volume and the total measurement error.

7. An electronic device, characterized in that: The method comprises a processor and a memory, wherein the memory stores computer-readable instructions, and when the computer-readable instructions are executed by the processor, the method according to any one of claims 1 to 4 is executed.

8. A storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the method according to any one of claims 1 to 4 is executed.

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