Operation method of gene analyzer sample loading table with automatic calibration function

Abstract

The invention discloses an operation method of a sample loading table of a gene analyzer with an automatic calibration function, the gene analyzer is composed of the following components: a sensor mechanism comprises an optical encoder, a non-contact capacitive sensor and a camera, an execution mechanism comprises a stepping motor and an electric push rod, and the electric push rod is connected with the sensor mechanism. The gene analyzer is used in cooperation with an execution mechanism through a sensor mechanism, and the method comprises the following steps: a) calibration; and b) height calibration. After the gene analyzer is set and started, a calibration plate is placed on a sample loading table, the type of the plate is selected through software, the system automatically drives the sample loading table to move to a calibration reference point, a positioning mark of the calibration plate is shot through a built-in camera, the positioning mark is compared with a software preset coordinate, and the calibration of the sample loading table is realized through micro pressure feedback of a capillary sample inlet. Whether the hole center is aligned or not is judged, the deviation value of each point is calculated through software, a linear compensation table is generated, and therefore self-calibration is completed, and the detection precision is improved.

Description

Technical Field

[0001] This invention relates to the field of gene analyzer technology, specifically to an operating method for a sample stage of a gene analyzer with automatic calibration. Background Technology

[0002] Gene analyzers are core devices used to analyze the DNA / RNA sequences, structures, and variations of organisms. By detecting the size, quantity, and sequence information of nucleic acid molecules, they provide crucial data for life science research, medical diagnosis, agricultural breeding, and other fields. Their core technologies include electrophoretic separation, fluorescent labeling detection, and data analysis algorithms, enabling full automation from sample input to result output.

[0003] According to a patent published on the China Patent Network, the patent title is: Automatic Calibration Method, Device, and Gene Analyzer for Sample Stage of Gene Analyzer, patent number: CN116218649B. This invention proposes an operation method for a sample stage of a gene analyzer with automatic calibration. The method includes: controlling a three-dimensional moving component to move the sample stage, moving the positioning column of the sample stage to the detection position corresponding to the laser ranging device; when the positioning column moves to the detection position corresponding to the laser ranging device, acquiring the current coordinates of the positioning column and using these coordinates as reference position coordinates; calculating the target position coordinates corresponding to the target tube based on the reference position coordinates and the relative positional relationship between the positioning column and the target tube in the sample plate; calculating the movement path of the target tube to the horizontal position coordinates of the capillary assembly's sample needle based on the target position coordinates; and controlling the three-dimensional moving component to move the sample stage according to the movement path to move the target tube to the horizontal position coordinates of the capillary assembly's sample needle. This invention can easily and quickly achieve automatic calibration between the capillary assembly's sample needle and the tube in the sample plate.

[0004] The above-mentioned method for operating a sample stage of a gene analyzer with automatic calibration involves setting a calibration structure in the gene analyzer, installing and fixing a sample plate on the sample stage, accurately detecting the position coordinates of the positioning column on the sample stage, using the position coordinates of the positioning column as the reference position coordinates, calculating the target position coordinates corresponding to the target tube based on the reference position coordinates and the relative position relationship between the positioning column and the target tube in the sample plate, calculating the movement path of the target tube to the horizontal position coordinates of the sample needle of the capillary assembly based on the target position coordinates, and controlling the three-dimensional moving component to move the sample stage according to the movement path to move the target tube to the horizontal position coordinates of the sample needle of the capillary assembly, thereby achieving horizontal calibration of the sample stage.

[0005] Existing gene analyzers require the sample loading stage to be aligned in advance during operation, so that the tube of the sample plate placed on the sample loading stage and the sample loading needle of the capillary assembly can be accurately calibrated. Frequent automated operation reduces its accuracy, affects the work, and reduces the safety of using the gene analyzer. Summary of the Invention

[0006] To address the problems mentioned in the background art, the present invention aims to provide an operation method for a sample stage of a gene analyzer with automatic calibration, which has the advantage of improved accuracy calibration. It solves the problem that gene analyzers need to align the sample stage in advance during operation, so that the tube of the sample plate placed on the sample stage and the sample needle of the capillary assembly can be accurately calibrated. Frequent automated operation causes the accuracy to decrease and affects the work.

[0007] To achieve the above objectives, the present invention provides the following technical solution: an operation method for a sample stage of a gene analyzer with automatic calibration, wherein the gene analyzer consists of the following components: the sensor mechanism includes an optical encoder, a non-contact capacitive sensor and a camera; and the actuator includes a stepper motor and an electric push rod.

[0008] As a preferred embodiment of the present invention, the gene analyzer is used in conjunction with a sensor mechanism and an actuator.

[0009] As a preferred embodiment of the present invention, the steps include: a) calibration; b) height calibration; c) dynamic enhancement; d) compensation mechanism; e) AI database; f) plate type recognition; g) sample positioning assistance; and h) sample volume closed-loop control. Step a) Calibration; Based on the traditional optical encoder, a laser interferometer module is added to perform nanometer-level linear error mapping of the XY axis guide rail. The laser interferometer mirror is fixed on the upper sample stage, the transmitter is aligned with the reference point, and the upper sample stage is driven to traverse the entire stroke at a speed of 0.1 mm / s. The deviation between the actual displacement and the theoretical value is recorded at every 100 μm interval. The software generates a polynomial error compensation table, such as a second-order polynomial, to correct nonlinear errors such as bending caused by guide rail wear point by point. Step b) Height calibration; Contact probes are prone to errors due to mechanical wear, especially in scenarios with frequent lifting. Replace them with non-contact capacitive sensors. By detecting the capacitance value between the liquid surface of the sample well and the capillary tip, the distance resolution can be calculated in real time with a resolution of 1μm. Establish a capacitance value height mapping curve in a standard solution such as conductive buffer, such as 0.5mm corresponding to capacitance value C1 and 1.0mm corresponding to C2. When the sample stage is lifted, the sensor provides real-time feedback on the capacitance value, and the software automatically adjusts the Z-axis height to the target range, such as 0.8±0.02mm. Step c) Dynamic enhancement; When the sample loading stage moves rapidly at speeds >50mm / s, the vibration of the guide rail may cause positioning deviations, especially at the edge holes of the 96-hole plate. Install hydraulic dampers at both ends of the XY axis guide rail to shorten the vibration decay time from 50ms to 10ms. Adjust the preload of the lead screw nut to eliminate the backlash and reduce it from ±20μm to ±5μm. The preload torque can be precisely controlled by a torque wrench. Step d) Compensation mechanism: When the instrument is running, the motor heat may cause thermal expansion of the guide rail. For every 1°C increase in temperature of the aluminum guide rail, the length increases by 23ppm. Install a Pt100 temperature probe near the guide rail to monitor temperature changes in real time. The software automatically corrects the coordinates based on the temperature data. For example, when ΔT=5°C, the X-axis compensation is ΔX=23ppm×5×guide rail length. Record the laboratory ambient temperature before turning on the instrument every day. It is recommended to control the temperature at 22±1°C and increase the calibration frequency during high-temperature periods, such as once every 4 hours. Step e) AI Database: Analyze historical calibration data using machine learning algorithms to predict wear trends of mechanical components and automatically adjust compensation parameters to establish a calibration database. Record data such as XYZ axis deviation values, usage time, and sample type for each calibration. Train wear prediction models such as LSTM neural networks to identify the correlation between guide rail wear and usage frequency. For example, if the X-axis deviation increases by 0.5μm for every 1000 runs, the software adjusts the compensation coefficient in advance based on the prediction results. For example, it automatically triggers a calibration reminder before the expected deviation exceeds ±20μm. This is suitable for high-load operation scenarios such as inspecting ≥50 sample plates per day, reducing the frequency of manual calibration while maintaining accuracy. Step f) Plate type identification: When the device is compatible with 8-well, 96-well, and 384-well plates, the hole spacing error between different plate types, such as 9mm for 96-well plates vs. 4.5mm for 384-well plates, may cause calibration conflicts. A QR code scanner is installed in the sample chamber to read the type label of the plate, which contains information such as hole spacing and positioning hole coordinates. Calibration parameters are stored separately for each plate type, such as using Group A compensation table for 96-well plates and Group B for 384-well plates. The system automatically switches before loading the sample to avoid cross-plate type errors caused by sharing the same calibration parameters between different plate types. Especially in the 384-well plate scenario, the hole alignment rate is improved from 95% to 99.5%. Step g) Sample positioning assistance: Add a visual positioning camera, such as Baslerac A1920-155uc, with a resolution of 1920×1280 pixels to the sample chamber. With the help of the checkerboard calibration plate, the accuracy is ±0.1mm. The camera identifies the notches or positioning holes of the sample, calculates the angular deviation from the software coordinate system, such as rotation θ=0.5°, drives the rotation compensation of the sample stage, and confirms the edge position of the plate through image processing algorithms such as Canny edge detection. Corrects manual loading errors such as plate offset ≤0.3mm. The user only needs to roughly put the plate into the sample chamber, and the system automatically completes the precise positioning, reducing human placement errors. Step h) Closed-loop control of sample aspiration volume: When the stepper motor drives the sample aspiration, the actual sample aspiration volume may deviate from the set value by ±5% due to changes in liquid viscosity. A miniature pressure sensor, such as the Honeywell SCL series, is installed in the capillary tube to monitor the negative pressure change during sample aspiration in real time. When the sample aspiration volume is insufficient, such as setting 1μL but actually 0.8μL, the slope of the pressure curve is abnormal. The system automatically triggers a second aspiration, and the software generates a sample aspiration volume deviation report, marks the abnormal well positions and prompts for re-examination. The detection limit is reduced from 50pg DNA to 20pg, which is especially suitable for low starting amount samples such as ctDNA detection.

[0010] As a preferred embodiment of the present invention, the laser interferometer is based on the interference phenomenon of light. By measuring the phase difference change of the laser beam after it has passed through different paths, it can achieve high-precision measurement of physical quantities such as displacement, angle, and flatness. The laser beam emitted by the laser source is split into two paths by a beam splitter. The measurement beam illuminates the object under test, such as a reflector, and changes the optical path as the object moves. The reference beam returns through a fixed reflector and serves as a phase reference. The two beams merge to produce interference fringes, and the displacement of the object under test is calculated by the change in the fringes.

[0011] As a preferred embodiment of the present invention, the non-contact capacitive sensor is a device for measuring physical quantities based on the principle of capacitance change. It can sense parameters such as displacement, thickness, liquid level, and dielectric properties without direct contact with the object being measured. The basic structure consists of a capacitor plate: at least one fixed plate sensor probe and the object being measured are equivalent to another plate or a medium that affects the dielectric constant; an insulating layer: isolating the plate from the outside world and preventing leakage; materials such as ceramics and polytetrafluoroethylene; a signal conditioning circuit: converting capacitance changes into voltage, current, or digital signals such as LC oscillation circuits and operational amplifier circuits; and a shell and shield: a metal shield to suppress electromagnetic interference and ensure measurement stability.

[0012] As a preferred embodiment of the present invention, the hydraulic damper is a mechanical device that utilizes the viscous resistance of a liquid, typically hydraulic oil, to achieve buffering, vibration reduction, or speed control. Its core principle is to generate resistance through the flow of liquid in damping orifices or gaps, converting kinetic energy into heat energy, thereby suppressing vibration or smoothly controlling motion. The basic structure consists of a cylinder: a sealed cavity filled with hydraulic oil, usually made of high-strength steel or aluminum alloy; a piston: separating the cylinder into two cavities, with damping orifices or throttling gaps on its surface; a piston rod: connecting the piston to the external mechanical structure, requiring wear and corrosion resistance, such as chrome plating; end caps: sealing both ends of the cylinder, including oil inlets and sealing devices such as O-rings and dust seals; and a damping orifice / throttling valve: controlling the oil flow rate and determining the damping force, which can be designed as a fixed or adjustable orifice.

[0013] As a preferred embodiment of the present invention, the Pt100 temperature probe is a temperature sensor based on the platinum resistance temperature effect. Its core component is a platinum metal wire with a purity typically ≥99.99%. The resistance of the platinum resistance changes approximately linearly with temperature. By measuring the change in resistance, the temperature can be accurately calculated. The probe monitors the temperature of the sample stage in real time and converts the resistance signal into a digital quantity through an analog-to-digital converter (ADC). The system drives the heating / cooling module to adjust according to a preset temperature threshold, such as 25℃±0.2℃, to achieve automatic calibration.

[0014] As a preferred embodiment of the present invention, the AI ​​database is a technology that uses artificial intelligence algorithms to model, optimize, and dynamically adjust the equipment calibration process. Its core logic is to use historical calibration data and real-time feedback data from sensors to train the AI ​​model, enabling the system to autonomously learn calibration rules and dynamically adapt to factors such as equipment aging, environmental changes, and sample differences, thereby improving calibration accuracy and efficiency.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention, through the settings of a gene analyzer, after powering on, places the calibration plate on the sample loading stage, selects the plate type via software, and the system automatically drives the sample loading stage to the calibration reference point. The system uses a built-in camera to photograph the positioning mark of the calibration plate and compares it with the preset coordinates in the software. Through the micro-pressure feedback from the capillary inlet, it determines whether the plate is aligned with the center of the hole. The software calculates the deviation value of each point and generates a linear compensation table, thereby completing self-calibration and improving the detection accuracy. Attached Figure Description

[0016] Figure 1 This is a three-dimensional view of the optical encoder structure of the present invention; Figure 2 This is a three-dimensional view of the non-contact capacitive sensor structure of the present invention; Figure 3 This is a three-dimensional view of the camera structure of the present invention; Figure 4 This is a perspective view of the stepper motor structure of the present invention; Figure 5 This is a perspective view of the electric actuator structure of the present invention. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] like Figures 1 to 5As shown, the present invention provides an operation method for a sample stage of a gene analyzer with automatic calibration. The gene analyzer consists of the following components: the sensor mechanism includes an optical encoder, a non-contact capacitive sensor, and a camera; the actuator includes a stepper motor and an electric push rod.

[0019] The present invention is further configured such that the gene analyzer is used in conjunction with a sensor mechanism and an actuator.

[0020] The present invention is further configured such that the steps include: a) calibration; b) height calibration; c) dynamic enhancement; d) compensation mechanism; e) AI database; f) plate type recognition; g) sample positioning assistance; and h) sample volume closed-loop control. Step a) Calibration; Based on the traditional optical encoder, a laser interferometer module is added to perform nanometer-level linear error mapping of the XY axis guide rail. The laser interferometer mirror is fixed on the upper sample stage, the transmitter is aligned with the reference point, and the upper sample stage is driven to traverse the entire stroke at a speed of 0.1 mm / s. The deviation between the actual displacement and the theoretical value is recorded at every 100 μm interval. The software generates a polynomial error compensation table, such as a second-order polynomial, to correct nonlinear errors such as bending caused by guide rail wear point by point. Step b) Height calibration; Contact probes are prone to errors due to mechanical wear, especially in scenarios with frequent lifting. Replace them with non-contact capacitive sensors. By detecting the capacitance value between the liquid surface of the sample well and the capillary tip, the distance resolution can be calculated in real time with a resolution of 1μm. Establish a capacitance value height mapping curve in a standard solution such as conductive buffer, such as 0.5mm corresponding to capacitance value C1 and 1.0mm corresponding to C2. When the sample stage is lifted, the sensor provides real-time feedback on the capacitance value, and the software automatically adjusts the Z-axis height to the target range, such as 0.8±0.02mm. Step c) Dynamic enhancement; When the sample loading stage moves rapidly at speeds >50mm / s, the vibration of the guide rail may cause positioning deviations, especially at the edge holes of the 96-hole plate. Install hydraulic dampers at both ends of the XY axis guide rail to shorten the vibration decay time from 50ms to 10ms. Adjust the preload of the lead screw nut to eliminate the backlash and reduce it from ±20μm to ±5μm. The preload torque can be precisely controlled by a torque wrench. Step d) Compensation mechanism: When the instrument is running, the motor heat may cause thermal expansion of the guide rail. For every 1°C increase in temperature of the aluminum guide rail, the length increases by 23ppm. Install a Pt100 temperature probe near the guide rail to monitor temperature changes in real time. The software automatically corrects the coordinates based on the temperature data. For example, when ΔT=5°C, the X-axis compensation is ΔX=23ppm×5×guide rail length. Record the laboratory ambient temperature before turning on the instrument every day. It is recommended to control the temperature at 22±1°C and increase the calibration frequency during high-temperature periods, such as once every 4 hours. Step e) AI Database: Analyze historical calibration data using machine learning algorithms to predict wear trends of mechanical components and automatically adjust compensation parameters to establish a calibration database. Record data such as XYZ axis deviation values, usage time, and sample type for each calibration. Train wear prediction models such as LSTM neural networks to identify the correlation between guide rail wear and usage frequency. For example, if the X-axis deviation increases by 0.5μm for every 1000 runs, the software adjusts the compensation coefficient in advance based on the prediction results. For example, it automatically triggers a calibration reminder before the expected deviation exceeds ±20μm. This is suitable for high-load operation scenarios such as inspecting ≥50 sample plates per day, reducing the frequency of manual calibration while maintaining accuracy. Step f) Plate type identification: When the device is compatible with 8-well, 96-well, and 384-well plates, the hole spacing error between different plate types, such as 9mm for 96-well plates vs. 4.5mm for 384-well plates, may cause calibration conflicts. A QR code scanner is installed in the sample chamber to read the type label of the plate, which contains information such as hole spacing and positioning hole coordinates. Calibration parameters are stored separately for each plate type, such as using Group A compensation table for 96-well plates and Group B for 384-well plates. The system automatically switches before loading the sample to avoid cross-plate type errors caused by sharing the same calibration parameters between different plate types. Especially in the 384-well plate scenario, the hole alignment rate is improved from 95% to 99.5%. Step g) Sample positioning assistance: Add a visual positioning camera, such as Baslerac A1920-155uc, with a resolution of 1920×1280 pixels to the sample chamber. With the help of the checkerboard calibration plate, the accuracy is ±0.1mm. The camera identifies the notches or positioning holes of the sample, calculates the angular deviation from the software coordinate system, such as rotation θ=0.5°, drives the rotation compensation of the sample stage, and confirms the edge position of the plate through image processing algorithms such as Canny edge detection. Corrects manual loading errors such as plate offset ≤0.3mm. The user only needs to roughly put the plate into the sample chamber, and the system automatically completes the precise positioning, reducing human placement errors. Step h) Closed-loop control of sample aspiration volume: When the stepper motor drives the sample aspiration, the actual sample aspiration volume may deviate from the set value by ±5% due to changes in liquid viscosity. A miniature pressure sensor, such as the Honeywell SCL series, is installed in the capillary tube to monitor the negative pressure change during sample aspiration in real time. When the sample aspiration volume is insufficient, such as setting 1μL but actually 0.8μL, the slope of the pressure curve is abnormal. The system automatically triggers a second aspiration, and the software generates a sample aspiration volume deviation report, marks the abnormal well positions and prompts for re-examination. The detection limit is reduced from 50pg DNA to 20pg, which is especially suitable for low starting amount samples such as ctDNA detection.

[0021] The invention is further configured such that the laser interferometer is based on the interference phenomenon of light, and achieves high-precision measurement of physical quantities such as displacement, angle, and flatness by measuring the phase difference change of the laser beam after passing through different paths. The laser beam emitted by the laser source is split into two paths by a beam splitter. The measurement beam illuminates the object under test, such as a reflector, and changes the optical path as the object moves. The reference beam returns through a fixed reflector and serves as a phase reference. The two beams merge to produce interference fringes, and the displacement of the object under test is calculated by the change of the fringes.

[0022] The present invention is further configured such that the non-contact capacitive sensor is a device for measuring physical quantities based on the principle of capacitance change. It can sense parameters such as displacement, thickness, liquid level, and medium characteristics without direct contact with the object being measured. The basic structure consists of a capacitor plate: at least one fixed plate sensor probe and the object being measured are equivalent to another plate or a medium that affects the dielectric constant; an insulating layer: isolating the plate from the outside world and preventing leakage; materials such as ceramics and polytetrafluoroethylene; a signal conditioning circuit: converting capacitance changes into voltage, current, or digital signals such as LC oscillation circuits and operational amplifier circuits; and a shell and shield: a metal shield to suppress electromagnetic interference and ensure measurement stability.

[0023] The invention is further configured such that the hydraulic damper is a mechanical device that utilizes the viscous resistance of a liquid, typically hydraulic oil, to achieve buffering, vibration reduction, or speed control. Its core principle is to generate resistance through the flow of liquid in damping orifices or gaps, converting kinetic energy into heat energy, thereby suppressing vibration or smoothly controlling movement. The basic structure consists of a cylinder: a sealed cavity filled with hydraulic oil, typically made of high-strength steel or aluminum alloy; a piston: separating the cylinder into two cavities, with damping orifices or throttling gaps on its surface; a piston rod: connecting the piston to the external mechanical structure, requiring wear and corrosion resistance, such as chrome plating; end caps: sealing both ends of the cylinder, including oil inlets and sealing devices such as O-rings and dust seals; and a damping orifice / throttling valve: controlling the oil flow rate and determining the damping force, which can be designed as a fixed or adjustable orifice.

[0024] The present invention is further configured such that the Pt100 temperature probe is a temperature sensor based on the platinum resistance temperature effect. Its core component is a platinum metal wire with a purity typically ≥99.99%. The resistance of the platinum resistance changes approximately linearly with temperature. By measuring the change in resistance, the temperature can be accurately calculated. The probe monitors the temperature of the sample stage in real time and converts the resistance signal into a digital quantity through an analog-to-digital converter (ADC). The system drives the heating / cooling module to adjust according to a preset temperature threshold, such as 25℃±0.2℃, to achieve automatic calibration.

[0025] The present invention is further configured such that the AI ​​database is a technology that uses artificial intelligence algorithms to model, optimize and dynamically adjust the equipment calibration process. Its core logic is to use historical calibration data and real-time feedback data from sensors to train the AI ​​model, enabling the system to autonomously learn calibration rules and dynamically adapt to factors such as equipment aging, environmental changes, and sample differences, thereby improving calibration accuracy and efficiency.

[0026] The working principle and usage process of this invention: Upon power-on, the system automatically triggers the XY axis zeroing motion of the sample stage: the sample stage moves towards the preset origin until it triggers the origin limit switch (such as an infrared photocell or mechanical contact). At this time, the software records the coordinates as 0,0. The sample stage rises to its highest position below the capillary inlet. The Z-axis origin is confirmed using a contact probe to ensure the sample hole is perpendicularly aligned with the capillary. If zeroing fails, it may be due to guide rail jamming or sensor dust obstruction. The guide rail needs to be manually cleaned, and the limit switch status checked. The calibration plate is placed on the sample stage. By selecting the plate type through the software, the system automatically drives the sample stage to the calibration reference point, such as the diagonal position of the 1st, 12th, or 85th hole. The actual position is confirmed using the following methods: Optical detection: through... The built-in camera captures the positioning marks on the calibration plate and compares them with the preset coordinates in the software. Mechanical inspection: The system uses minute pressure feedback from the capillary inlet to determine if the plate is aligned with the center of the hole. If misalignment is detected, abnormal injection resistance is observed. The software calculates the deviation values ​​at each point and generates a linear compensation table, such as correcting the coordinates using a first-order linear equation. Recalibration is required when changing to different types of plate plates. Calibration solution is added to specific holes on the calibration plate. The system performs a Z-axis lifting test: the plate is raised to different heights, sample is attempted, and the sample volume is measured. The optimal Z-axis height is determined by a pressure sensor or sample volume feedback, and the software automatically saves this parameter. A rapid translation test is then performed: the plate moves back and forth 10 times at maximum speed in the X and Y axes. The software monitors the repeatability error of the motion trajectory using encoder data. If the error exceeds the limit, the acceleration and deceleration parameters of the motor need to be adjusted, such as increasing the acceleration and deceleration time or tightening the guide rail screws. The laser interferometer reflector is fixed on the upper sample stage, the transmitter is aligned with the reference point, and the upper sample stage is driven to traverse the entire stroke. The actual displacement and theoretical value deviation at intervals are recorded. The software generates a polynomial error compensation table to correct nonlinear errors point by point. The improved XY-axis positioning accuracy is suitable for precise positioning of small-volume samples. The contact probe can be easily replaced with a non-contact capacitance sensor. By detecting the capacitance value between the liquid surface in the sample well and the capillary tip, the distance is calculated in real time. A capacitance-height mapping curve is established in a standard solution such as conductive buffer solution. When the upper sample stage is raised, the sensor provides real-time feedback of the capacitance value, and the software automatically adjusts the Z-axis height to the target range, eliminating mechanical contact errors. To avoid liquid splashing or insufficient sample aspiration, this system is suitable for micro-samples. Hydraulic dampers, such as the THKSR series, are installed at both ends of the XY-axis guide rails to shorten the vibration decay time from 50ms to 10ms. Adjusting the preload of the lead screw nut eliminates backlash; the preload torque can be precisely controlled using a torque wrench. A Pt100 temperature probe is installed near the guide rails to monitor temperature changes in real time. The software automatically corrects the coordinates based on the temperature data. The laboratory ambient temperature should be recorded before each startup and ideally controlled at 22±1℃. The calibration frequency should be increased during high-temperature periods. Historical calibration data is analyzed using machine learning algorithms to predict the wear trend of mechanical components and automatically adjust compensation parameters. Data such as the XYZ-axis deviation, usage time, and sample type are recorded for each calibration to train a wear prediction model.The software identifies the correlation between guide rail wear and usage frequency, adjusting compensation coefficients in advance based on predictions. It automatically triggers calibration alerts before deviations exceed ±20μm, making it suitable for high-load operation scenarios. This reduces the frequency of manual calibration while maintaining accuracy. When the equipment is compatible with 8-panel, 96-well, and 384-well plates, hole spacing errors between different plate types may cause calibration conflicts. A QR code scanner is installed in the sample chamber to read the plate type label, including information such as hole spacing and positioning hole coordinates. Calibration parameters are stored separately for each plate type (e.g., 96-well plates use Group A compensation tables, 384-well plates use Group B). Automatic switching before loading avoids cross-plate type errors caused by sharing the same calibration parameters between different plate types. A visual positioning camera is added to the sample chamber to identify notches or positioning holes in the plates, calculates the angular deviation from the software coordinate system, and drives the plate rotation for compensation. Image processing algorithms are used for edge detection to confirm the plate's edge position, correcting for manual loading errors. Users only need to roughly place the plate into the sample chamber, and the system automatically completes precise positioning, reducing human placement errors. When the stepper motor drives sample aspiration, changes in liquid viscosity may cause deviations between the actual aspiration volume and the set value. A miniature pressure sensor is installed in the capillary tube to monitor negative pressure changes during aspiration in real time. When the aspiration volume is insufficient, the pressure curve slope becomes abnormal, and the system automatically triggers secondary aspiration. The software generates a sample volume deviation report, marks abnormal well positions, and prompts for re-checking. Through these technological upgrades, the sample loading stage can achieve 50μm-level positioning accuracy and nano-level aspiration control, directly improving the sensitivity detection limit and accuracy of gene analysis, making it particularly suitable for scenarios with extremely high sample accuracy requirements, such as tumor micro-mutation detection and non-invasive prenatal screening (NIPT).

[0027] In summary, the operation method of the sample stage of this gene analyzer with automatic calibration is as follows: The gene analyzer consists of the following components: a sensor mechanism including an optical encoder, a non-contact capacitive sensor, and a camera; and an actuator including a stepper motor and an electric push rod. During use, after powering on, the calibration plate is placed on the sample stage. The plate type is selected via software, and the system automatically drives the sample stage to the calibration reference point. The built-in camera captures the positioning marks on the calibration plate and compares them with the preset coordinates in the software. Through the feedback of minute pressure at the capillary inlet, it determines whether the alignment with the orifice center is achieved. The software calculates the deviation values ​​at each point and generates a linear compensation table, thereby completing self-calibration and improving detection accuracy. This solves the problem that gene analyzers require pre-alignment of the sample stage during operation to ensure accurate calibration of the sample plate tube and the capillary assembly's sample needle, and that frequent automated operation leads to decreased accuracy and affects work.

[0028] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0029] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An operating method for a sample stage of a gene analyzer with automatic calibration, characterized in that; The gene analyzer is composed of the following components, the sensor mechanism includes optical encoder, non-contact capacitive sensor and camera, the execution mechanism includes stepper motor and electric push rod.

2. The method of claim 1, wherein: The gene analyzer is used by the sensor mechanism and the execution mechanism.

3. The method of claim 1 or 2, wherein the method further comprises: The steps include step a) calibration; step b) height calibration; step c) dynamic enhancement; step d) compensation mechanism; step e) AI database; step f) plate type identification; step g) sample positioning assistance; and step h) sample suction amount closed loop control. ​ Step a) calibration; on the basis of traditional optical encoder, install laser interferometer module to measure nanoscale linear error of XY axis guide rail, fix laser interferometer mirror on sample loading table, align the emission end to the reference point, drive the sample loading table to traverse the full stroke at a speed of 0.1 mm / s, record the actual displacement and theoretical value deviation every 100 μm interval, and the software generates a polynomial error compensation table such as a second-order polynomial, which corrects the bending caused by non-linear errors such as guide rail wear point by point. Step b) height calibration; Contact probes are prone to errors due to mechanical wear, especially in frequent lifting scenarios, replace them with non-contact capacitive sensors, which detect the capacitance value between the sample hole liquid surface and the capillary tip, and calculate the spacing resolution in real time to 1 μm, and establish a capacitance value height mapping curve in standard liquids such as conductive buffer, such as 0.5 mm corresponding to capacitance value C1, 1.0 mm corresponding to C2, when the sample loading table is lifted, the sensor feeds back the capacitance value in real time, and the software automatically adjusts the Z-axis height to the target interval such as 0.8±0.02 mm. Step c) dynamic enhancement; when the sample loading table moves at a speed of >50 mm / s, guide rail vibration may cause positioning deviation, especially in the edge hole of a 96-well plate, install hydraulic dampers at both ends of the XY axis guide rail, reduce the vibration decay time from 50 ms to 10 ms, adjust the screw nut pre-tightening force, eliminate the reverse clearance from ±20 μm to ±5 μm, and the pre-tightening torque can be accurately controlled by a torque wrench. Step d) compensation mechanism; when the instrument is running, motor heating may cause guide rail thermal expansion, and the length of the aluminum guide rail increases by 23 ppm for every 1℃ temperature rise, install a Pt100 temperature probe near the guide rail to monitor temperature changes in real time, and the software automatically corrects the coordinates according to the temperature data, such as ΔT=5℃, ΔX=23ppm×5×guide rail length, record the laboratory environment temperature before starting each day, and it is recommended to control it at 22±1℃, and increase the calibration frequency during high temperature period, such as every 4 hours. Step e) AI database; analyze historical calibration data through machine learning algorithms to predict mechanical component wear trends and automatically adjust compensation parameters, establish a calibration database: record XYZ axis deviation values, usage time, sample type, etc. for each calibration, train wear prediction models such as LSTM neural networks, identify the correlation between guide rail wear and usage frequency, such as X-axis deviation increasing by 0.5μm every 1000 runs, and software adjusting compensation coefficients in advance based on prediction results, such as automatically triggering calibration reminders before predicted deviation exceeds ±20μm, suitable for high-load running scenarios such as detecting ≥50 sample plates per day, reducing manual calibration frequency while maintaining accuracy; Step f) Plate type recognition; when the device simultaneously supports 8-union, 96-well, and 384-well plates, different plate types may cause calibration conflicts, such as 96-well plate hole spacing 9mm vs. 384-well plate hole spacing 4.5mm, install a two-dimensional code scanner in the sample chamber, read the type label of the sample plate, such as containing hole spacing, positioning hole coordinates, etc. Store calibration parameters for each plate type separately, such as using A group compensation table for 96-well plates and B group for 384-well plates, automatically switch before sampling to avoid cross-plate errors caused by sharing the same calibration parameters for different plate types, especially in 384-well plate scenarios, hole alignment rate improves from 95% to 99.5%; Step g) Sample plate positioning assistance; add a visual positioning camera such as Basler acA1920-155uc with a resolution of 1920×1280 pixels to the sample chamber, achieve an accuracy of ±0.1mm with a chessboard calibration plate, identify the gap or positioning hole of the sample plate, calculate the angle deviation with the software coordinate system such as rotation θ=0.5°, and drive the sample table to rotate for compensation, confirm the plate edge position through image processing algorithms such as Canny edge detection, correct manual loading errors such as plate offset ≤0.3mm, users only need to roughly place the plate into the sample chamber, and the system automatically completes precise positioning, reducing human placement errors; Step h) Closed-loop control of sample suction volume; when a stepper motor drives sample suction, actual sample suction volume may deviate from the set value due to changes in liquid viscosity, such as ±5%, install a micro pressure sensor such as Honeywell SCL series in the capillary pipeline to monitor the negative pressure change during sample suction in real time, when the sample suction volume is insufficient, such as set to 1μL and actual 0.8μL, the pressure curve slope is abnormal, the system automatically triggers secondary re-suction, the software generates a sample suction volume deviation report, marks abnormal holes and prompts for review, and the lower detection limit is reduced from 50pg DNA to 20pg, especially suitable for low initial volume samples such as ctDNA detection.

4. The method of claim 1, wherein: The laser interferometer is based on the interference phenomenon of light, which measures the phase difference change of laser beams after passing through different paths to achieve high-precision measurement of physical quantities such as displacement, angle, and flatness. The light beam emitted by the laser source is divided into two paths by a beam splitter, the measurement beam: irradiates onto the measured object such as a mirror, and the reference beam: returns through a fixed mirror as a phase reference. The two beams converge to produce interference fringes, and the displacement of the measured object is calculated by the change in the fringes.

5. The method of claim 1, wherein: The non-contact capacitive sensor is a device for measuring physical quantities based on the principle of capacitance change. It can sense displacement, thickness, liquid level, medium characteristics, etc. without direct contact with the measured object. The basic structure consists of a capacitive plate, at least one fixed plate sensor probe and the measured object equivalent to another plate or medium affecting the dielectric constant; an insulating layer to isolate the plate from the outside world to prevent leakage; a signal conditioning circuit to convert capacitance changes into voltage, current or digital signals; a housing and shielding to suppress electromagnetic interference and ensure measurement stability.

6. The method of claim 1, wherein: The hydraulic damper is a mechanical device that uses the viscous resistance of liquid, usually hydraulic oil, to achieve buffering, vibration reduction or control of movement speed. Its core principle is to convert kinetic energy into heat energy by generating resistance through the flow of liquid in the damping hole or gap, thereby suppressing vibration or smoothly controlling movement. The basic structure consists of a cylinder, which is a sealed cavity filled with hydraulic oil, made of high-strength steel or aluminum alloy; a piston, which separates the cylinder into two cavities and has damping holes or throttling gaps on its surface; a piston rod, which connects the piston to the external mechanical structure and requires wear resistance and corrosion resistance such as chrome plating; an end cap, which seals both ends of the cylinder and contains an oil injection port and sealing devices such as O-rings and dust seals; and a damping hole / throttle valve, which controls oil flow and determines the damping force size, which can be designed as a fixed aperture or adjustable. The Pt100 temperature probe is a temperature sensor based on the platinum resistance temperature effect. Its core element is a platinum wire with a purity of ≥99.99%. The resistance of the platinum resistor changes approximately linearly with temperature, and the temperature can be accurately calculated by measuring the resistance change. The probe monitors the temperature of the sample table in real time, converts the resistance signal to digital quantity through the analog-to-digital conversion module ADC, and the system drives the heating / cooling module to adjust according to the preset temperature threshold such as 25℃±0.2℃, achieving automatic calibration.

7. The method of claim 1, wherein: The AI database is a technology that models, optimizes and dynamically adjusts the calibration process of equipment through artificial intelligence algorithms. Its core logic is to train AI models using historical calibration data and real-time feedback data from sensors, allowing the system to learn calibration rules autonomously and dynamically adapt to equipment aging, environmental changes, sample differences and other factors, thereby improving calibration accuracy and efficiency.

8. The method of claim 1, wherein: ​

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