High-precision micro incubator and multi-mode control method, equipment and medium thereof

Abstract

The invention provides a high-precision micro incubator and a multi-mode control method, equipment and medium thereof, the uniformity of a thermal field is realized through a quick response temperature control framework of a U-shaped circulating air duct and a PTC array, the hysteresis limitation of traditional steam humidification is broken through by adopting a humidity compensation scheme of a sodium polyacrylate hydrogel base material and directional atomization, and the humidity compensation efficiency is improved. A temperature and humidity feedforward decoupling model is established, and the humidity oscillation phenomenon in the heating process is eliminated; a quartz glass optical window is developed and is compatible with 40 * objective lens observation; a U-shaped closed-loop gas loop is constructed, CO2 / O2 concentration dynamic compensation (the response time is less than 15 seconds) is realized, and an HEPA (High Efficiency Particulate Air) high-efficiency filtering module waste gas filtering technology is used; a weight-adjustable dynamic multi-objective optimization algorithm is adopted, parameter priority requirements of different growth stages of the similar organs are met, and an emergency power supply system based on a super capacitor ensures that data in a power-off environment are not lost.

Description

Technical Field

[0001] The present invention relates to the technical field of intersection of biomedical engineering and precision instruments, and in particular to a high-precision micro-incubator and a multi-modal control method, equipment, and medium thereof. Background Art

[0002] Current organoid culture technologies primarily rely on traditional cell culture incubators or customized microfluidic devices, which have the following key drawbacks:

[0003] 1. Insufficient environmental control accuracy

[0004] Traditional incubators rely on global temperature control (±0.5°C) and passive humidity maintenance (water tray evaporation), which cannot meet the local microenvironmental stability requirements of organoids (for example, neural organoids require temperature fluctuations of less than 0.2°C). Gas regulation relies on periodic air exchange, resulting in CO2 / O2 concentration fluctuations exceeding ±1%, affecting metabolic sensitivity.

[0005] 2. Poor compatibility for microscopic observation

[0006] Most existing equipment uses a closed cavity design, and microscopic imaging requires frequent opening and closing of the cabin door, causing a sudden drop in temperature (>3°C / time) and humidity imbalance (RH fluctuation >15%), which destroys the stability of the three-dimensional structure of the organoids.

[0007] 3. High-throughput adaptation defects

[0008] The volume of a single chamber in a commercial incubator is typically greater than 5L, making it impossible to independently control multiple batches. While microfluidic chips can reduce volume, they carry the risk of pipeline clogging and lack the ability to dynamically compensate for gas composition.

[0009] 4. Low degree of intelligence

[0010] Existing systems often use independent PID control loops, which can lead to coupled interference in temperature and humidity regulation (for example, heating can cause humidity to drop by as much as 2.5%RH / °C) and a lack of redundant control strategies in the event of sensor failure.

[0011] 5. Gas environment stability defects

[0012] Traditional equipment requires continuous input of large amounts of compensatory gas (typical flow rate >300mL / min) during the maintenance phase, leading to the following problems: excessive gas consumption (average daily gas consumption >5L), significantly increasing experimental costs; frequent gas exchange causes temperature and humidity fluctuations, and periodic oscillations in gas concentration.

[0013] Therefore, it is necessary to provide a new method to solve the above technical problems. Summary of the Invention

[0014] In order to achieve the above-mentioned objects and other advantages of the present invention, a first object of the present invention is to provide a high-precision micro-incubator, comprising a box body with a circulating air duct, a box cover assembly, a temperature control module, a humidity control module, a gas circuit, a temperature and humidity sensor, an optical window, and a main control unit;

[0015] The box cover assembly is mounted on the box body, and the optical window is detachably mounted on the box cover assembly;

[0016] The temperature control module includes a PTC heating array and a circulation fan. The PTC heating array is arranged at the air inlet of the circulation duct, and the circulation fan is installed in the circulation duct.

[0017] The humidity control module includes a sodium polyacrylate hydrogel layer pre-adsorbed with deionized water, and a piezoelectric atomizer installed in the air flow channel;

[0018] The gas circuit integrates a CO2 sensor, an O2 sensor and a filter module;

[0019] The temperature and humidity sensor is arranged in the cavity of the box;

[0020] The main control unit establishes a temperature and humidity feedforward decoupling model to eliminate humidity oscillation during the heating process, and is equipped with a dynamic multi-objective optimization algorithm with adjustable weights to meet the parameter priority requirements of organoids at different growth stages.

[0021] Furthermore, the box cover assembly includes a box cover and a culture chamber cover plate, the box cover is mounted on the box body, the culture chamber cover plate is mounted on the box cover, and the optical window is detachably mounted on the culture chamber cover plate.

[0022] Furthermore, the box cover assembly also includes a fluororubber sealing ring groove, which is arranged on the joint surface of the box body and the box cover. When the compression amount of the fluororubber sealing ring groove is 30%, the cavity leakage rate is less than 0.01% vol / h.

[0023] Furthermore, the circulating air duct is a U-shaped circulating air duct, and the U-shaped circulating air duct includes a strip-shaped return air port and a semicircular air inlet that are symmetrically arranged.

[0024] Furthermore, the temperature control module further includes a guide grid, and the guide grid is arranged at the semicircular air inlet.

[0025] Furthermore, the guide grid includes three guide plates and a semicircular guide ring distributed in parallel at an inclination angle of 20-45°. The guide plates are arranged at the inlet of the semicircular air inlet, and the semicircular guide ring is arranged at the outlet of the semicircular air inlet. The semicircular guide ring and the tapered flow channel of the circulating air duct form a Venturi effect.

[0026] Furthermore, the PTC heating array adopts a radial fin layout.

[0027] Furthermore, the number of the piezoelectric atomizing sheets is two, and the two groups of piezoelectric atomizing sheets are installed in the air flow channel at an angle of 15-60 degrees;

[0028] The water retention capacity of the sodium polyacrylate hydrogel layer is ≥5g / cm 3 , and the atomization direction of the piezoelectric atomizer is at an angle of 15-60° to the main airflow direction.

[0029] Furthermore, the gas circuit is a U-shaped closed-loop gas circuit, which is connected to an external gas source through a quick-plug check joint. In the initial stage, premixed gas is injected at a high flow rate to make the gas in the cavity reach the set value. In the maintenance stage, it is switched to a micro-flow mode, and metabolic consumption gas is compensated in real time through PID feedback.

[0030] Furthermore, the filtration module adopts a HEPA filter element, and the air inlet and outlet of the U-shaped closed-loop gas circuit are both equipped with HEPA filter elements. The surface of the HEPA filter element is hydrophobic treated, and the pressure loss in a 90% RH environment is <50Pa, and the gas humidity loss rate is <0.5% RH / h.

[0031] Furthermore, the optical window is a quartz glass optical window, the surface of the quartz glass optical window is coated with an anti-reflection film and the distance between the quartz glass optical window and the microscope objective lens is 1.0±0.05mm.

[0032] Furthermore, the control equation of the temperature and humidity feedforward decoupling model is:

[0033]

[0034] The main control unit uses the fuzzy PID algorithm to dynamically adjust the control parameters, where the proportional coefficient and time constant are:

[0035] K p =K p0 +α·ΔT rms

[0036]

[0037] Among them, k1 and k2 are empirical coefficients, ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, t is the time variable, T is the hot air temperature, and RH is the relative humidity;

[0038] The multi-objective optimization function is:

[0039] min(ω1·|T set -T|+ω2·|RHset -RH|+ω3·ΔGas)

[0040] Among them, ΔGas is the CO2 / O2 concentration deviation, and the weight coefficients ω1, ω2, and ω3 are dynamically adjusted according to the cultivation stage.

[0041] Furthermore, the main control unit adopts a customized Modbus-RTU communication protocol, the data frame format is address + function code + data + CRC16 check, and MQTT over TLS1.3 encrypted transmission is enabled in WiFi mode.

[0042] Furthermore, it also includes a supercapacitor emergency power supply module to maintain the power supply of the sensor and complete the storage of environmental parameters after a power outage.

[0043] A second object of the present invention is to provide a multimodal control method for a high-precision micro-incubator, which is applied to the above-mentioned high-precision micro-incubator and includes the following steps:

[0044] Optimize the PTC heating array layout based on COMSOL thermal field simulation to ensure that the temperature difference in the horizontal and vertical directions of the cavity meets the preset conditions;

[0045] A temperature and humidity feedforward decoupling model is established, and its control equation is:

[0046]

[0047] Among them, k1 and k2 are empirical coefficients, T is the hot air temperature, and RH is the relative humidity;

[0048] The fuzzy PID algorithm is used to dynamically adjust the control parameters, where the proportional coefficient and time constant are:

[0049] K p =K p0 +α·ΔT rms

[0050]

[0051] Where, ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, and t is the time variable;

[0052] Dynamically adjust the weight coefficients of the multi-objective optimization function according to the growth stage of the organoid;

[0053] min(ω1·|T set -T|+ω2·|RH set -RH|+ω3·ΔGas)

[0054] Among them, ΔGas is the CO2 / O2 concentration deviation, and ω1, ω2, and ω3 are weight coefficients.

[0055] Furthermore, the method further includes a gas injection mode switching step:

[0056] When |C 实测 -C 设定 When |>0.5%, high flow injection mode is started;

[0057] When |C 实测 -C 设定 When |<0.2%, switch to micro compensation mode;

[0058] Among them, C 实测 is the measured gas concentration, C 设定 is the set gas concentration.

[0059] Furthermore, the method further comprises the steps of:

[0060] When a sensor failure is detected, it switches to model predictive control mode and starts the supercapacitor to complete data backup after power failure.

[0061] Furthermore, the temperature difference in the horizontal direction and the temperature difference in the vertical direction of the cavity satisfying the preset conditions is configured to make the temperature difference in the horizontal direction of the cavity ≤ 0.08°C and the temperature difference in the vertical direction ≤ 0.12°C;

[0062] The empirical coefficient α has a value range of 0.05-0.15, and the value range of β has a value range of 0.01-0.03;

[0063] During the proliferation phase, ω1=0.6, ω2=0.3, and ω3=0.1 were set; during the differentiation phase, ω1=0.3, ω2=0.2, and ω3=0.5 were set.

[0064] A third object of the present invention is to provide a computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the steps of the above method when executing the computer program.

[0065] A fourth object of the present invention is to provide a computer-readable storage medium having a computer program stored thereon, wherein the computer program implements the steps of the above method when executed by a processor.

[0066] Compared with the prior art, the present invention has the following beneficial effects:

[0067] The present invention provides a high-precision micro-incubator and a multi-modal control method thereof, which has the following advantages:

[0068] In the automated culture of organoids, refined coordinated control of temperature, humidity, and gas composition is achieved to meet the long-term culture needs of various organoids such as nerves, liver, and intestines.

[0069] In high-throughput drug screening, it supports seamless integration of multi-channel independent regulation and microscopic observation, significantly improving experimental efficiency and data reliability.

[0070] In the construction of pathological models, dynamic gas environment simulation and real-time imaging feedback are used to provide precise control tools for tumor microenvironment research.

[0071] The miniaturized integrated design significantly reduces the size of the device, supports flexible expansion of multiple modules and wireless networking, and adapts to the needs of complex experimental scenarios.

[0072] Break through the response bottleneck of traditional temperature control systems, achieve sub-degree Celsius temperature stability and rapid humidity compensation, and effectively avoid the impact of environmental fluctuations on samples.

[0073] Innovative gas drive system and chamber isolation technology eliminate mechanical vibration and heat source interference, ensuring the cleanliness of the culture environment and long-term operational stability.

[0074] Optimizes energy transmission paths, significantly reduces energy consumption and improves device endurance, and supports power outage emergency protection and secure data storage.

[0075] Compatible with high-resolution microscopy imaging, dynamic observation can be completed without opening the cover, avoiding the risk of sample damage or contamination caused by traditional operations.

[0076] The modular quick-disassembly structure simplifies the maintenance process and reduces the complexity and cost of equipment operation and maintenance.

[0077] Rapid environment construction: Through high-flow air intake technology, the time to reach the initial gas concentration standard is shortened to 90 seconds, meeting the urgent experimental needs in drug screening.

[0078] Ultra-low gas consumption: The sealed chamber design combined with the micro-compensation mode reduces the gas cost of long-term experiments.

[0079] Reduce the consumption of experimental consumables and manual operation costs, and help scientific research institutions and enterprises reduce costs and increase efficiency.

[0080] Accelerate the process of organoid model construction and drug screening, and provide efficient technical support for precision medicine and personalized treatment.

[0081] Promote the development of biomedical instruments towards intelligence and miniaturization, and promote laboratory automation upgrades and space resource optimization.

[0082] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and to implement it according to the contents of the description, the following preferred embodiments of the present invention are described in detail with reference to the accompanying drawings. The specific implementation methods of the present invention are given in detail by the following embodiments and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0083] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of this application. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0084] Figure 1 This is a schematic diagram of the high-precision micro incubator structure;

[0085] Figure 2 Schematic diagram of the internal structure of the box;

[0086] Figure 3 It is the top view of the box;

[0087] Figure 4 Flowchart of the multimodal control method for a high-precision micro-incubator;

[0088] Figure 5 It is a schematic diagram of computer equipment;

[0089] Figure 6 A schematic diagram of a computer-readable storage medium.

[0090] In the figure: 10, box body; 11, quartz glass; 12, screw; 13, PTC heater pressing piece; 14, PTC heater array; 15, semicircular guide ring; 16, mounting groove; 17, strip return air outlet; 18, tapered flow channel; 19, guide plate; 110, circulating fan mounting groove; 20, box cover; 21, sealing ring groove; 30, culture chamber cover; 31, optical window; 32, nut; 40, back cover; 50, main control unit; 51, micro temperature and humidity sensor; 52, quick-insert check connector; 53, O2 sensor; 54, precision temperature and humidity sensor; 55, CO2 sensor. DETAILED DESCRIPTION

[0091] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. It should be noted that, without conflict, the embodiments or technical features described below can be arbitrarily combined to form new embodiments.

[0092] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative work shall fall within the scope of protection of the present invention.

[0093] The figure numbers in this application are only used to distinguish the various steps in the scheme and are not used to limit the execution order of the various steps. The specific execution order is subject to the description in the specification.

[0094] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0095] Example 1

[0096] A high-precision micro incubator, such as Figure 1-Figure 3 As shown, it includes a box body 10 with a circulating air duct, a box cover assembly, a temperature control module, a humidity control module, a gas circuit, a temperature and humidity sensor, an optical window 31, and a main control unit 50;

[0097] The box cover assembly is mounted on the box body, and the optical window is detachably mounted on the box cover assembly;

[0098] The temperature control module includes a PTC heating array and a circulation fan. The PTC heating array is arranged at the air inlet of the circulation duct, and the circulation fan is installed in the circulation duct.

[0099] The humidity control module includes a sodium polyacrylate hydrogel layer pre-adsorbed with deionized water, and a piezoelectric atomizer installed in the air flow channel;

[0100] The gas circuit integrates a CO2 sensor 55, an O2 sensor 53 and a filter module;

[0101] The temperature and humidity sensor is arranged in the cavity of the box;

[0102] The main control unit establishes a temperature and humidity feedforward decoupling model to eliminate humidity oscillation during the heating process, and is equipped with a dynamic multi-objective optimization algorithm with adjustable weights to meet the parameter priority requirements of organoids at different growth stages.

[0103] In some embodiments, as Figure 1-Figure 3 As shown, the circulating air duct is a U-shaped circulating air duct, which includes a symmetrically arranged strip return air port 17 and a semicircular air inlet, that is, the strip return air port and the air inlet are symmetrically arranged on both sides of the chamber, and the CFD simulation flow rate uniformity is greater than 98%;

[0104] This embodiment adopts a fast-response temperature control architecture of a U-shaped circulation air duct + PTC array to achieve thermal field uniformity.

[0105] This embodiment uses a brushless DC fan. Specifically, a brushless DC micro fan (rotating at 25,000 rpm) is embedded in the circulation fan mounting slot 110, achieving full cavity ventilation in 2.3 seconds. When the cavity volume is 500 mL, the full air circulation period is ≤ 2 seconds.

[0106] In some embodiments, as Figure 1-Figure 3 As shown, the gas circuit is a U-shaped closed-loop gas circuit, and the arrow indicates the direction of the gas flow: the U-shaped closed-loop gas circuit is connected to the gas circuit through a quick-plug check connector 52 (leakage rate <1×10 -6 mbar·L / s) to connect to external gas source.

[0107] This embodiment can achieve rapid gas construction and low-consumption maintenance:

[0108] In the initial stage, the premixed gas is injected at a high flow rate to make the gas in the cavity reach the set value; for example, in the initial stage, the premixed gas is injected at a high flow rate of >500ml / min to make the gas in the cavity reach the set value within 90 seconds;

[0109] During the maintenance phase, the system switches to micro-flow mode and compensates for metabolic gas consumption in real time through PID feedback.

[0110] Furthermore, the filtration module adopts a HEPA filter element, and the air inlet and outlet of the U-shaped closed-loop gas circuit are both equipped with HEPA filter elements. For example, the air inlet and outlet are equipped with H13 grade HEPA filter elements. The surface of the HEPA filter element is hydrophobic treated, and the pressure loss in a 90% RH environment is <50Pa, and the gas humidity loss rate is <0.5% RH / h.

[0111] The quick-plug check connector 52 is connected to the external air source to achieve sterile air intake through the HEPA filter. The connector on the other side is connected to the one-way valve to achieve one-way air outlet, which can also achieve sterile air outlet through the HEPA filter.

[0112] In this embodiment, the U-shaped closed-loop gas circuit uses a Cubic SRH-10B CO2 sensor (accuracy ±0.1%) and a LuminOx LOX-02 O2 sensor (accuracy ±0.1%). The O2 sensor (LuminOx LOX-02) and CO2 sensor (Cubic SRH-10B) are placed in parallel at the bend of the circuit, reducing detection response time to 12 seconds.

[0113] like Figure 1 As shown, the temperature and humidity sensors include a micro temperature and humidity sensor 51 and a precision temperature and humidity sensor 54. In this embodiment, an SHT45 temperature and humidity sensor (temperature ±0.1°C, humidity ±1.0%RH) is arranged in the chamber.

[0114] This embodiment realizes dynamic compensation of CO2 / O2 concentration (response time <15 seconds) by constructing a U-shaped closed-loop gas circuit and adopts a HEPA high-efficiency filtration module.

[0115] In some embodiments, as Figure 1As shown, the box cover assembly includes a box cover 20 and a culture chamber cover plate 30. The box cover is installed on the box body, the culture chamber cover plate is installed on the box cover, and the optical window 31 is detachably installed on the culture chamber cover plate.

[0116] Furthermore, the box cover assembly also includes a fluororubber sealing ring groove 21, which is arranged on the joint surface of the box body and the box cover, specifically installed in the installation groove 16. When the compression amount of the fluororubber sealing ring groove is 30%, the cavity leakage rate is <0.01% vol / h.

[0117] In this embodiment, the housing 10 is precision milled from 6061-T6 aluminum alloy, anodized on the surface, and has an internal volume of 800 mL. A quartz glass cap 11 is also installed at the bottom of the housing 10. The housing cover 20 is fastened to the housing 10 via M2 screws 12. A fluororubber sealing ring groove 21 is provided on the joint surface. When the compression reaches 30%, the leakage rate is less than 0.01% vol / h. The culture chamber cover 30 is embedded with 1.0 mm thick ultra-thin borosilicate glass with a light transmittance of >92% (wavelength 400-700 nm). Quick disassembly is achieved by hand-tightening the nut 32.

[0118] In some embodiments, the temperature control module further includes a guide grille, and the air inlet is provided with the guide grille, that is, the guide grille is provided at the semicircular air inlet.

[0119] Furthermore, the guide grid includes three guide plates 19 distributed in parallel at an inclination angle of 20-45° and a semicircular guide ring 15. Preferably, the three guide plates distributed in parallel at an inclination angle of 30° are arranged at the inlet of the semicircular air inlet. For example, three rows of 3D printed guide plates are arranged at the inlet of the air inlet, and the semicircular guide ring is arranged at the outlet of the semicircular air inlet. The dead zone volume accounts for <0.5%. In this embodiment, the curvature radius of the semicircular guide ring is 8 mm. The semicircular guide ring and the tapered flow channel 18 of the circulating air duct form a Venturi effect, and the flow rate is increased by 15%.

[0120] The three guide plates 19 are arranged in parallel at an angle of 30 degrees, so that the gas passes through the PTC heating array evenly. Computational fluid dynamics (CFD) verification shows that the standard deviation of the air flow velocity in the cavity is less than 0.05 m / s.

[0121] COMSOL simulation verification: At 37°C, the temperature difference in the horizontal direction of the cavity is ≤0.08°C, and the temperature difference in the vertical direction is ≤0.12°C.

[0122] In some embodiments, the PTC heating array adopts a radial fin layout, and a PTC heating array with a radial fin layout is provided inside the air inlet, specifically installed on one side of the semicircular guide ring. Figure 2As shown, the PTC heater array 14 is composed of a plurality of PTC heater pressing sheets 13. In this embodiment, two groups of radial fin-layout PTC ceramic heater sheets (single group power 25W, spacing 1mm) are embedded in the air inlet and dynamically controlled by PWM driving MOS tubes.

[0123] In some embodiments, the number of the piezoelectric atomizer sheets is two, for example, two sets of piezoelectric ceramic ultrasonic atomizer sheets (resonant frequency 1.7 MHz, atomization volume ≥ 3 mL / h) are integrated, and the two sets of piezoelectric atomizer sheets are installed in the air flow channel at an angle of 15-60 degrees, and the atomization direction of the piezoelectric atomizer sheets is at an angle of 15-60 degrees to the main air flow direction. Preferably, the two sets of piezoelectric atomizer sheets are installed in the air flow channel at an angle of 30 degrees, and the atomization direction of the piezoelectric atomizer sheets is at an angle of 30 degrees to the main air flow direction.

[0124] The water retention capacity of the sodium polyacrylate hydrogel layer is ≥5g / cm 3 , maintain basic humidity 80% RH for 72 hours.

[0125] This embodiment uses a sodium polyacrylate hydrogel substrate and a directional atomization humidity compensation solution to break through the hysteresis limitation of traditional steam humidification.

[0126] In some embodiments, the optical window is a quartz glass optical window compatible with a 40× objective lens. The surface of the quartz glass optical window is coated with an anti-reflection film and the distance between the window and the microscope objective lens is 1.0±0.05 mm.

[0127] like Figure 1-Figure 2 As shown, the main control unit is mounted on the rear cover 40, which is mounted on the box. In some embodiments, the main control unit uses an ESP32-S3 chip, supports a PID operation cycle of 1ms, WiFi / RS485 communication, and adopts a custom Modbus-RTU communication protocol. The data frame format is address + function code + data + CRC16 checksum. In WiFi mode, MQTT over TLS1.3 encrypted transmission is enabled to achieve multi-parameter feedback control of carbon dioxide and oxygen concentrations, temperature, humidity, etc.

[0128] Furthermore, the control equation of the temperature and humidity feedforward decoupling model is:

[0129]

[0130] The main control unit uses the fuzzy PID algorithm to dynamically adjust the control parameters, where the proportional coefficient and time constant are:

[0131] K p =K p0 +α·ΔT rms

[0132]

[0133] Among them, k1 and k2 are empirical coefficients, ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, t is the time variable, T is the hot air temperature, and RH is the relative humidity;

[0134] The multi-objective optimization function is:

[0135] min(ω1·|T set -T|+ω2·|RH set -RH|+ω3·ΔGas)

[0136] Among them, ΔGas is the CO2 / O2 concentration deviation, and the weight coefficients ω1, ω2, and ω3 are dynamically adjusted according to the culture stage (e.g., the proliferation stage focuses on temperature, and the differentiation stage focuses on gas).

[0137] This example establishes a temperature and humidity feedforward decoupling model to eliminate humidity fluctuations during the heating process. Feedforward compensation eliminates humidity interference during the heating process, enabling humidity-following control with temperature-prioritized regulation. A dynamic multi-objective optimization algorithm with adjustable weights is employed to address parameter priority requirements at different organoid growth stages.

[0138] In some embodiments, a supercapacitor emergency power supply module is also included to maintain power supply to the sensor and complete environmental parameter storage after a power outage.

[0139] For example, the capacity of the supercapacitor emergency power supply module used is ≥10F, which can maintain the power supply to the sensor for ≥30 seconds and complete the environmental parameter storage after power failure.

[0140] This embodiment develops an emergency power supply system based on supercapacitors to ensure that data is not lost in power outages. When a sensor failure is detected, it automatically switches to model predictive control (MPC) mode; after a power outage, the supercapacitor is used to complete data backup.

[0141] In high-throughput drug screening applications, a 96-well organoid chip was placed in the chamber, and the gradient temperature (36.5-37.5°C, 0.1°C step) and CO2 concentration (4%-6%) were set through the APP;

[0142] The system automatically records the growth rate of organoids in each well and identifies the optimal combination of culture conditions through a machine learning model (CNN algorithm).

[0143] The multimodal control method corresponding to the high-precision micro-incubator provided in this embodiment can refer to the corresponding description in the following multimodal control method embodiment, and will not be repeated here.

[0144] The present invention provides a miniature organoid incubator that integrates ultra-precise gas composition and temperature control, dynamic humidity compensation, in-situ microscope imaging adaptation, and wireless networking functions. It supports rapid gas environment construction and low gas consumption maintenance, and is particularly suitable for the automated culture and long-term monitoring of organoids in high-throughput drug screening.

[0145] Example 2

[0146] A multimodal control method for a high-precision micro-incubator is applied to the above-mentioned high-precision micro-incubator. For a detailed description of the high-precision micro-incubator, please refer to the corresponding description in the above-mentioned high-precision micro-incubator embodiment, which will not be repeated here. Figure 4 As shown, the method includes the following steps:

[0147] S100, based on COMSOL thermal field simulation, optimize the PTC heating array layout so that the temperature difference in the horizontal plane and the vertical direction of the cavity meet the preset conditions; for example, the temperature difference in the horizontal plane of the cavity is ≤0.08°C, and the temperature difference in the vertical direction is ≤0.12°C;

[0148] S110. Establish a temperature and humidity feedforward decoupling model, whose control equation is:

[0149]

[0150] Among them, k1 and k2 are empirical coefficients, T is the hot air temperature, and RH is the relative humidity;

[0151] This embodiment eliminates the interference of temperature control on humidity through feedforward compensation.

[0152] S120, using fuzzy PID algorithm to dynamically adjust control parameters, where the proportional coefficient and time constant are:

[0153] K p =K p0 +α·ΔT rms

[0154]

[0155] Where ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, and t is the time variable;

[0156] In this embodiment, the empirical coefficient α has a value range of 0.05-0.15, and the empirical coefficient β has a value range of 0.01-0.03.

[0157] S130, dynamically adjusting the weight coefficients of the multi-objective optimization function according to the organoid growth stage;

[0158] min(ω1·|T set -T|+ω2·|RHset -RH|+ω3·ΔGas)

[0159] Among them, ΔGas is the CO2 / O2 concentration deviation, and ω1, ω2, and ω3 are weight coefficients.

[0160] In this embodiment, ω1=0.6, ω2=0.3, and ω3=0.1 are set during the proliferation phase, and ω1=0.3, ω2=0.2, and ω3=0.5 are set during the differentiation phase.

[0161] In some embodiments, the gas injection mode switching step is further included:

[0162] When |C 实测 -C 设定 When |>0.5%, high flow injection mode is started;

[0163] When |C 实测 -C 设定 When |<0.2%, switch to micro compensation mode.

[0164] Among them, C 实测 is the measured gas concentration, C 设定 is the set gas concentration.

[0165] In some embodiments, the steps further include:

[0166] When a sensor failure is detected, it switches to model predictive control (MPC) mode and starts the supercapacitor to complete data backup after power failure.

[0167] Example 3

[0168] A computer device 200, such as Figure 5 As shown, the system includes a memory 210, a processor 220, and a computer program 230 stored in the memory and executable on the processor. When the processor executes the computer program, the steps of a multimodal control method for a high-precision micro-incubator are implemented. For a detailed description of the method, please refer to the corresponding description in the above method embodiment and will not be repeated here.

[0169] Example 4

[0170] A computer-readable storage medium such as Figure 6 As shown, a computer program is stored thereon, and when the computer program is executed by the processor, the steps of a multimodal control method for a high-precision micro incubator are implemented. For a detailed description of the method, reference can be made to the corresponding description in the above method embodiment, and no further details will be given here.

[0171] The number of devices and processing scales described herein are intended to simplify the description of the present invention. Applications, modifications, and variations of the present invention will be readily apparent to those skilled in the art.

[0172] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and implementation methods. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

[0173] The apparatus, computer device, non-volatile computer storage medium, and method provided in the embodiments of this specification correspond to each other. Therefore, the apparatus, computer device, and non-volatile computer storage medium also have similar beneficial technical effects as the corresponding method. Since the beneficial technical effects of the method have been described in detail above, the beneficial technical effects of the corresponding apparatus, computer device, and non-volatile computer storage medium will not be repeated here.

[0174] Those skilled in the art will also appreciate that, in addition to implementing the controller in pure computer-readable program code, it is entirely possible to implement the same functionality by programming the method steps logically, such as through logic gates, switches, application-specific integrated circuits, programmable logic controllers, and embedded microcontrollers. Therefore, such a controller can be considered a hardware component, and the devices included therein for implementing various functions can also be considered structures within the hardware component. Alternatively, the devices for implementing various functions can be considered both software units implementing the method and structures within the hardware component.

[0175] The systems, devices, or units described in the above embodiments can be implemented by computer chips or physical devices, or by products with certain functions. For ease of description, the above devices are described separately by function, with each unit described separately. Of course, when implementing one or more embodiments of this specification, the functions of each unit can be implemented in the same or multiple software and / or hardware components.

[0176] Those skilled in the art will appreciate that the embodiments of this specification may be provided as methods, systems, or computer program products. Therefore, the embodiments of this specification may take the form of a complete hardware embodiment, a complete software embodiment, or an embodiment combining software and hardware. Furthermore, the embodiments of this specification may take the form of a computer program product implemented on one or more computer-usable storage media (including but not limited to magnetic disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0177] This specification is described with reference to the flowcharts and / or block diagrams of the methods, devices (systems), and computer program products according to the embodiments of this specification. It should be understood that each process and / or box in the flowchart and / or block diagram, as well as the combination of processes and / or boxes in the flowchart and / or block diagram, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, an embedded processor, or other programmable data processing device to produce a machine, so that the instructions executed by the processor of the computer or other programmable data processing device generate instructions for implementing the processes in the flowchart and / or block diagram. Figure 1 a process or multiple processes and / or boxes Figure 1 A device that provides the functions specified in a block or multiple blocks.

[0178] These computer program instructions may also be stored in a computer readable memory that can direct a computer or other programmable data processing device to work in a specific manner, so that the instructions stored in the computer readable memory produce an article of manufacture comprising an instruction device, which implements the process Figure 1 a process or multiple processes and / or boxes Figure 1 The function specified in one or more boxes.

[0179] These computer program instructions can also be loaded onto a computer or other programmable data processing device so that a series of operational steps are executed on the computer or other programmable device to produce a computer-implemented process, thereby providing the instructions executed on the computer or other programmable device for implementing the process. Figure 1 a process or multiple processes and / or boxes Figure 1 A step that specifies a function in one or more boxes.

[0180] It should also be noted that the terms "comprises," "includes," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, commodity, or apparatus that includes a series of elements includes not only those elements but also other elements not explicitly listed, or includes elements inherent to such process, method, commodity, or apparatus. In the absence of further limitations, an element defined by the phrase "comprises a ..." does not exclude the presence of other identical elements in the process, method, commodity, or apparatus that includes the element.

[0181] This specification may be described in the general context of computer-executable instructions executed by a computer, such as program units. Generally, program units include routines, programs, objects, components, data structures, and the like that perform specific tasks or implement specific abstract data types. The specification may also be practiced in distributed computing environments where tasks are performed by remote processing devices connected via a communications network. In a distributed computing environment, program units may be located in local and remote computer storage media, including storage devices.

[0182] The various embodiments in this specification are described in a progressive manner. Similar parts between the various embodiments can be referred to in conjunction with each other. Each embodiment focuses on the differences between the other embodiments. In particular, the system embodiments are generally similar to the method embodiments, so the description is relatively simple. For relevant parts, refer to the description of the method embodiments.

[0183] The foregoing is merely an example of the present invention and is not intended to limit the present invention to one or more embodiments. It will be apparent to those skilled in the art that various modifications and variations may be made to the present invention to one or more embodiments. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention to one or more embodiments shall be included within the scope of the claims of the present invention to one or more embodiments.

Claims

1. A high-precision micro incubator, characterized by: It includes a box body with a circulating air duct, a box cover assembly, a temperature control module, a humidity control module, a gas circuit, a temperature and humidity sensor, an optical window, and a main control unit; The box cover assembly is mounted on the box body, and the optical window is detachably mounted on the box cover assembly; The temperature control module includes a PTC heating array and a circulation fan. The PTC heating array is arranged at the air inlet of the circulation duct, and the circulation fan is installed in the circulation duct. The humidity control module includes a sodium polyacrylate hydrogel layer pre-adsorbed with deionized water, and a piezoelectric atomizer installed in the air flow channel; The gas circuit integrates a CO2 sensor, an O2 sensor and a filter module; The temperature and humidity sensor is arranged in the cavity of the box; The main control unit establishes a temperature and humidity feedforward decoupling model to eliminate humidity oscillation during the heating process, and is equipped with a dynamic multi-objective optimization algorithm with adjustable weights to meet the parameter priority requirements of organoids at different growth stages.

2. A high-precision micro-incubator according to claim 1, characterized in that: The box cover assembly comprises a box cover and a culture chamber cover plate. The box cover is mounted on the box body, the culture chamber cover plate is mounted on the box cover, and the optical window is detachably mounted on the culture chamber cover plate.

3. A high-precision micro-incubator according to claim 2, characterized in that: The box cover assembly also includes a fluororubber sealing ring groove, which is arranged on the joint surface of the box body and the box cover. When the compression amount of the fluororubber sealing ring groove is 30%, the cavity leakage rate is less than 0.01% vol / h.

4. The high-precision micro incubator according to claim 1, characterized in that: The circulating air duct is a U-shaped circulating air duct, and the U-shaped circulating air duct includes a strip-shaped return air port and a semicircular air inlet that are symmetrically arranged.

5. A high-precision micro-incubator according to claim 4, characterized in that: The temperature control module further includes a guide grid, which is arranged at the semicircular air inlet.

6. The high-precision micro-incubator according to claim 5, characterized in that: The guide grid includes three guide plates and a semicircular guide ring distributed in parallel at an inclination angle of 20-45°. The guide plates are arranged at the inlet of the semicircular air inlet, and the semicircular guide ring is arranged at the outlet of the semicircular air inlet. The semicircular guide ring and the tapered flow channel of the circulating air duct form a Venturi effect.

7. The high-precision micro-incubator according to claim 1, characterized in that: The PTC heating array adopts a radial fin layout.

8. The high-precision micro-incubator according to claim 1, characterized in that: There are two groups of piezoelectric atomizers, and the two groups of piezoelectric atomizers are installed in the air flow channel at an angle of 15-60 degrees; The water retention capacity of the sodium polyacrylate hydrogel layer is ≥5g / cm 3 , and the atomization direction of the piezoelectric atomizer is at an angle of 15-60° to the main airflow direction.

9. The high-precision micro-incubator according to claim 1, characterized in that: The gas circuit is a U-shaped closed-loop gas circuit, which is connected to an external gas source through a quick-plug check joint. In the initial stage, premixed gas is injected at a high flow rate to make the gas in the cavity reach the set value. In the maintenance stage, it is switched to a micro-flow mode, and metabolic consumption gas is compensated in real time through PID feedback.

10. The high-precision micro incubator according to claim 9, characterized in that: The filtration module adopts a HEPA filter element, and the air inlet and outlet of the U-shaped closed-loop gas circuit are both equipped with HEPA filter elements. The surface of the HEPA filter element is hydrophobic treated, and the pressure loss in a 90% RH environment is <50Pa, and the gas humidity loss rate is <0.5% RH / h.

11. The high-precision micro-incubator according to claim 1, characterized in that: The optical window is a quartz glass optical window, the surface of which is coated with an anti-reflection film and the distance between the quartz glass optical window and the microscope objective lens is 1.0±0.05mm.

12. The high-precision micro-incubator according to claim 9, characterized in that: The control equation of the temperature and humidity feedforward decoupling model is: The main control unit uses the fuzzy PID algorithm to dynamically adjust the control parameters, where the proportional coefficient and time constant are: K p =K p0 +α·ΔT rms Among them, k1 and k2 are empirical coefficients, ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, t is the time variable, T is the hot air temperature, and RH is the relative humidity; The multi-objective optimization function is: min(ω1·|T set -T|+ω2·|RH set -RH|+ω3·ΔGas) Among them, ΔGas is the CO2 / O2 concentration deviation, and the weight coefficients ω1, ω2, and ω3 are dynamically adjusted according to the cultivation stage.

13. The high-precision micro-incubator according to claim 1, characterized in that: The main control unit adopts a custom Modbus-RTU communication protocol, the data frame format is address + function code + data + CRC16 check, and MQTT over TLS1.3 encrypted transmission is enabled in WiFi mode.

14. The high-precision micro-incubator according to claim 1, characterized in that: It also includes a supercapacitor emergency power supply module to maintain sensor power supply and complete environmental parameter storage after power outage.

15. A multimodal control method for a high-precision micro-incubator, applied to the high-precision micro-incubator according to any one of claims 1 to 14, characterized in that: The following steps are involved: Optimize the PTC heating array layout based on COMSOL thermal field simulation to ensure that the temperature difference in the horizontal and vertical directions of the cavity meets the preset conditions; A temperature and humidity feedforward decoupling model is established, and its control equation is: Among them, k1 and k2 are empirical coefficients, T is the hot air temperature, and RH is the relative humidity; The fuzzy PID algorithm is used to dynamically adjust the control parameters, where the proportional coefficient and time constant are: K p =K p0 +α·ΔT rms Where, ΔT rms is the temperature root mean square deviation, α and β are empirical coefficients, and t is the time variable; Dynamically adjust the weight coefficients of the multi-objective optimization function according to the growth stage of the organoid; min(ω1·|T set -T|+ω2·|RH set -RH|+ω3·ΔGas) Among them, ΔGas is the CO2 / O2 concentration deviation, and ω1, ω2, and ω3 are weight coefficients.

16. The multimodal control method of a high-precision micro-incubator according to claim 15, characterized in that: It also includes the gas injection mode switching steps: When |C 实测 -C 设定 When |>0.5%, high flow injection mode is started; When |C 实测 -C 设定 When |<0.2%, switch to micro compensation mode; Among them, C 实测 is the measured gas concentration, C 设定 is the set gas concentration.

17. The multimodal control method of a high-precision micro-incubator according to claim 15, characterized in that: Also includes the steps: When a sensor failure is detected, it switches to model predictive control mode and starts the supercapacitor to complete data backup after power failure.

18. The multimodal control method of a high-precision micro-incubator according to claim 15, characterized in that: The temperature difference in the horizontal direction and the temperature difference in the vertical direction of the cavity satisfying the preset conditions is configured to make the temperature difference in the horizontal direction of the cavity ≤ 0.08°C and the temperature difference in the vertical direction ≤ 0.12°C; The empirical coefficient α has a value range of 0.05-0.15, and the value range of β has a value range of 0.01-0.03; During the proliferation phase, ω1=0.6, ω2=0.3, and ω3=0.1 were set; during the differentiation phase, ω1=0.3, ω2=0.2, and ω3=0.5 were set.

19. A computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein: When the processor executes the computer program, the steps of the method according to any one of claims 15 to 18 are implemented.

20. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the steps of the method according to any one of claims 15 to 18 are implemented.

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