Intelligent monitoring system and method for bacterial culture equipment based on big data

Through the intelligent supervision system of bacterial culture equipment based on big data, the problems of low automation level of traditional systems and instability of the culture environment are solved, dynamic control and data accuracy of the bacterial culture environment are achieved, and simulation capabilities of a variety of drug use schemes are provided. Provides a reliable reference for clinical medication.

CN119101598APending Publication Date: 2024-12-10SUZHOU FOO-CHI BIOMEDICAL TECHNOLOGY CO LTD
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Patent Information

Application Number
CN202411231776.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-09-04
Publication Date
2024-12-10

AI Technical Summary

Technical Problem

The traditional bacterial culture system has a single function and low degree of automation, and cannot dynamically adjust the medium concentration, resulting in unstable bacterial culture environment and affecting the accuracy of pharmacokinetics and pharmacokinetics research data.

Method used

An intelligent supervision system for bacterial culture equipment based on big data was designed, including upper computer unit, central control unit, execution unit, culture fluid circuit unit, filter unit and sampling unit. The data is monitored and feedbacked by sensors, and the culture fluid is automatically controlled. Recycle, replenish, temperature and atmosphere to ensure the stability of the cultivation environment.

Benefits of technology

It improves the degree of automation of the experiment, realizes dynamic update of the culture medium, reduces the deviation of pharmacokinetics and pharmacokinetics research data, provides a simulation ability of a variety of drug regimens, and provides a reliable reference for clinical drug use.

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Abstract

The invention relates to the technical field of bacterial culture, in particular to a bacterial culture equipment intelligent supervision system and method based on big data, and the system comprises an upper computer unit which is used for generating and issuing a control instruction; and the central control unit is used for receiving the control instruction issued by the upper computer unit, controlling the execution unit to complete each control instruction, receiving feedback of the sensor bound with the execution unit, generating running state data corresponding to the execution unit, and feeding back the running state data to the upper computer unit. The device is convenient to operate and high in automation degree, convenience can be provided for users, a solution is provided for in-vitro research of a dynamic sterilization model, the inhibiting or killing effect of various different medication schemes on bacteria can be simulated, reference is provided for clinical medication, dynamic updating of a culture medium is achieved in the simulation implementation process, and the dynamic updating effect of the culture medium is improved. And the stability of a bacterial culture environment is ensured, so that the deviation of PK / PD research data obtained according to bacterial culture is reduced.
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Description

Technical Field

[0001] The present invention relates to the technical field of bacterial culture, and in particular to an intelligent monitoring system and method for bacterial culture equipment based on big data. Background Art

[0002] Pharmacokinetics is a science that studies the dynamic laws of drug concentration changes over time after the drug enters the body, while pharmacodynamics mainly studies the effect of drugs on pathogens, which can reflect the antimicrobial effect and clinical efficacy of drugs. In recent years, pharmacokinetics and pharmacokinetics have received more and more attention. In vitro PK / PD research data are essential for selecting doses and regimens for patients, establishing drug sensitivity breakpoints, and ultimately improving clinical dosage regimens. Currently, the more commonly used models for in vitro PK / PD include static models and dynamic models. The traditional bacterial culture system has a single function, a simple structure, and a low degree of automation, which cannot meet the multi-faceted needs of users well; it mainly relies on manual operation, which is not only cumbersome and time-consuming, but also cannot dynamically adjust the concentration of the culture medium during bacterial culture, and cannot ensure the stability of the bacterial culture environment, which makes the PK / PD research data obtained based on bacterial culture have large deviations.

[0003] In the prior art, Chinese patent CN110607344A discloses a method for constructing and applying a PK / PD model, and the implementation process of the model is fully manual. Therefore, to build a PK / PD model, a highly automated and integrated process is required to ensure the stability of the bacterial culture environment during the experiment. Summary of the invention

[0004] The purpose of the present invention is to provide a big data-based intelligent monitoring system and method for bacterial culture equipment to solve the problems raised in the above-mentioned background technology.

[0005] In order to solve the above technical problems, the present invention provides the following technical solutions: an intelligent monitoring system for bacterial culture equipment based on big data, the system comprising: A host computer unit, the host computer unit is used to generate and issue control instructions; The central control unit is used to receive control instructions issued by the host computer unit, control the execution unit to complete each control instruction, receive feedback from the sensor bound to the execution unit, generate operation status data corresponding to the execution unit, and feed it back to the host computer unit; The execution unit includes a culture fluid path unit, a filtering unit and a sampling unit. The culture liquid circuit unit is used to control the culture liquid circuit in the bacterial culture device; The filtering unit controls the filtering fiber in the bacterial culture device to recover or filter the culture solution transmitted by the culture bottle in the culture solution path, the filtered solution flows back into the culture bottle, and the recovered solution flows into the waste liquid barrel through the peristaltic pump; The sampling unit is used to control the sampling operation of the culture solution in the culture solution path of the bacteria culture device.

[0006] Furthermore, the bacterial culture device includes a culture bottle and a filter fiber, and the two ends of the culture bottle and the filter fiber are connected to form a loop through a liquid pipeline and a diaphragm pump; the filter fiber is also connected to a waste liquid bucket through a liquid pipeline and a diaphragm pump for replacing the culture liquid in the culture bottle; A magnetic stirrer is arranged inside the culture bottle, and an electromagnet is arranged at the bottom of the culture bottle to drive the magnetic stirrer to rotate; a waterproof and breathable membrane is arranged on the culture bottle to control the gas exchange between the culture bottle and the outside world; a plurality of sensors are arranged in the culture bottle to monitor the status information in the culture bottle.

[0007] Furthermore, the culture fluid circuit unit includes a control module, a detection module and a liquid adding module. The control module is used to control the temperature and gas concentration in the culture bottle; In the present invention, temperature control is achieved by Peltier; atmosphere control is achieved by connecting a gas cylinder with a gas valve and a sterile filter element; when in use, a suitable atmosphere (air, CO2 or nitrogen) can be directly added to the space above the culture bottle according to the atmosphere requirements of bacterial culture; The detection module is used to detect the liquid level and pH value of the culture solution in the culture bottle; the liquid level is monitored and acquired by a liquid level sensor built into the culture bottle, and the pH value is detected and controlled by adding a preset indicator and by a color sensor through a color change. The present invention monitors the liquid level height in the culture bottle because both the waste liquid recovery operation and the sampling operation will reduce the volume of the culture medium in the culture bottle and require subsequent replenishment. The amount of culture medium solution that needs to be replenished is further determined by monitoring the difference in liquid level height.

[0008] The liquid adding module is used to control the type and amount of solution added into the culture bottle.

[0009] Furthermore, when the filtering unit recovers the culture fluid transmitted by the culture bottle, the waste liquid recovery monitoring concentration threshold fluctuation interference quantity corresponding to the current time is generated in combination with the monitoring information of the bacterial culture equipment in the historical data. The acquisition method is as follows: Step 1, extract the culture solution concentrations monitored by the sensor at each time point in the time period between two adjacent waste liquid recovery operations in the historical data, and construct a culture solution concentration fluctuation data pair, recorded as (t, Ct), wherein t represents the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation; Ct represents the culture solution concentration value corresponding to the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation when t is the interval, and the value of Ct is equal to 10 to the reciprocal of the pH value corresponding to t. Step 2: connect the corresponding coordinate points of the culture solution concentration fluctuation data corresponding to each time point in the time period between any two adjacent waste liquid recovery operations in a plane rectangular coordinate system in sequence, and obtain a curve of the relationship between the culture solution concentration and time corresponding to the two adjacent waste liquid recovery operations, wherein the plane rectangular coordinate system is constructed with o as the origin, the interval time as the x-axis, and the culture solution concentration as the y-axis; Step 3: Mark the coordinate points with the largest culture solution concentration among the corresponding coordinate points of each change relationship curve when the horizontal coordinates in the plane rectangular coordinate system are the same, and fit the coordinate points of each mark in the plane rectangular coordinate system according to the preset function model y= to generate a reference function of the change relationship between the culture solution concentration and time corresponding to the current time, recorded as function (x); Step 4: Obtain the average value of the interval delay from each time the waste liquid recovery operation instruction is generated to the start of the corresponding waste liquid recovery operation instruction in the historical data, recorded as TD, and calculate the waste liquid recovery monitoring concentration threshold fluctuation interference corresponding to the current time, recorded as AF, AF=(r+1)·function(TE-TD), Wherein, TE represents the predicted value of the interval between the time point of the next waste liquid recovery operation instruction based on the current time and the time of the previous waste liquid recovery operation; the value of r is equal to the average value of the data fitting deviation corresponding to each time point in the time period from the previous waste liquid recovery operation time based on the current time to the current time; The data fitting deviation corresponding to any time point is recorded as M, then M=(Cs-Cp) / Cp, Cs represents the culture solution concentration actually monitored by the sensor at the corresponding time point; Cp represents the culture solution concentration corresponding to the corresponding time point in function (x); TE=function -1 (AR / (r+1)), Among them, AR represents the waste liquid recovery monitoring concentration threshold preset in the database; function -1 () represents the inverse function of function(); function -1(AR / (r+1)) represents the horizontal coordinate value corresponding to the culture medium concentration of function (x) being AR / (r+1); r represents the function fitting deviation coefficient; The filtering unit determines the generation condition of the waste liquid recovery operation instruction according to the waste liquid recovery monitoring concentration threshold fluctuation interference amount AF corresponding to the current time, When the sensor detects that the concentration of the culture fluid transferred from the culture bottle to the filter fiber before recovery is less than or equal to AF, it is determined to immediately generate a waste liquid recovery operation instruction; otherwise, the filter unit does not perform the recovery operation of the culture fluid transferred from the culture bottle; The waste liquid recovery operation instruction includes the waste liquid recovery time and the waste liquid recovery amount. The waste liquid recovery time is the time when the corresponding waste liquid recovery operation instruction is generated, and the waste liquid recovery amount is a threshold value set manually.

[0010] Furthermore, the liquid adding module controls the type of solution added to the culture bottle to be the same as the type of culture medium solution selected when initially culturing bacteria in the current culture bottle; When the liquid adding module controls the amount of solution added to the culture bottle, the corresponding liquid adding operation instruction includes the liquid adding operation time and the liquid adding amount; the liquid adding operation time is the time point corresponding to when the liquid level height fluctuation value monitored by the sensor in the most recent unit time is less than or equal to the preset fluctuation value and the absolute value of the difference between the corresponding liquid level height and the preset liquid level height is less than or equal to the preset liquid level deviation; The liquid addition amount is the volume of culture liquid corresponding to the liquid level height difference between the liquid level height corresponding to the corresponding liquid addition operation time and the liquid level height preset value; The unit time is a constant preset in the database; the liquid level height fluctuation value is equal to the difference between the maximum liquid level height and the minimum liquid level height in the corresponding time period.

[0011] Furthermore, the sampling unit performs a sampling operation on the culture fluid at a preset time interval, and the amount of each sampling is preset.

[0012] A method for intelligent monitoring of bacterial culture equipment based on big data, the method comprising the following steps: S1. Setting the operating parameters of the bacterial culture equipment through the host computer unit and the central control unit; S2. Receive feedback data from the sensor bound to the execution unit corresponding to the bacterial culture equipment through the central control unit, generate running status data corresponding to the execution unit, and feed it back to the host computer unit; S3. According to the operation status data of the execution unit fed back by the central control unit and the operation parameter setting result corresponding to the bacterial culture equipment, the host computer unit generates a control instruction corresponding to the execution unit, and controls the execution unit through the central control unit; The control instructions include instructions for controlling the recovery of waste liquid, instructions for controlling the collection operation of culture liquid, instructions for controlling the environmental temperature in the culture bottle, instructions for controlling the environmental atmosphere in the culture bottle, instructions for controlling the renewal of culture medium and instructions for controlling the environmental temperature of sample storage.

[0013] Furthermore, the operating parameters include the operating time of the culture fluid circuit unit in the execution unit, the ambient temperature in the culture bottle, the ambient atmosphere, the culture medium volume, the pH value, the culture medium renewal judgment conditions, the waste liquid recovery conditions in the filtration unit, the single recovery volume of the waste liquid, and the sample storage temperature, sampling volume and sampling frequency in the sampling unit.

[0014] Compared with the prior art, the beneficial effects achieved by the present invention are: the present invention is easy to operate, has a high degree of automation, can provide convenience for users, provides a solution for in vitro research on dynamic bactericidal models, can simulate the inhibitory or killing effects of various different medication regimens on bacteria, and provide a reference for clinical medication. In the process of simulation, the culture medium can be dynamically updated to ensure the stability of the bacterial culture environment, thereby reducing the deviation of PK / PD research data obtained based on bacterial culture. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings: Figure 1 It is a structural schematic diagram of an intelligent monitoring system for bacterial culture equipment based on big data of the present invention. DETAILED DESCRIPTION

[0016] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0017] See also Figure 1 The present invention provides a technical solution: a method for intelligent monitoring of bacterial culture equipment based on big data, the method comprising the following steps: S1. Set the operating parameters of the bacterial culture equipment through the upper computer unit and the central control unit; the operating parameters include the operating time of the culture liquid circuit unit in the execution unit, the ambient temperature in the culture bottle, the ambient atmosphere, the culture medium volume, the pH value, the culture medium update judgment condition, the waste liquid recovery condition in the filtration unit, the single recovery amount of the waste liquid, and the sample storage temperature, sampling volume and sampling frequency in the sampling unit.

[0018] S2. Receive feedback data from the sensor bound to the execution unit corresponding to the bacterial culture equipment through the central control unit, generate running status data corresponding to the execution unit, and feed it back to the host computer unit; S3. According to the operation status data of the execution unit fed back by the central control unit and the operation parameter setting result corresponding to the bacterial culture equipment, the host computer unit generates a control instruction corresponding to the execution unit, and controls the execution unit through the central control unit; The control instructions include instructions for controlling the recovery of waste liquid, instructions for controlling the collection operation of culture liquid, instructions for controlling the environmental temperature in the culture bottle, instructions for controlling the environmental atmosphere in the culture bottle, instructions for controlling the renewal of culture medium and instructions for controlling the environmental temperature of sample storage.

[0019] A big data-based intelligent monitoring system for bacterial culture equipment, the system comprising: A host computer unit, the host computer unit is used to generate and issue control instructions; The central control unit is used to receive control instructions issued by the host computer unit, control the execution unit to complete each control instruction, receive feedback from the sensor bound to the execution unit, generate operation status data corresponding to the execution unit, and feed it back to the host computer unit; The execution unit includes a culture fluid path unit, a filtering unit and a sampling unit. The filtering unit controls the filtering fiber in the bacterial culture device to recover or filter the culture solution transmitted by the culture bottle in the culture solution path, the filtered solution flows back into the culture bottle, and the recovered solution flows into the waste liquid barrel through the peristaltic pump; The bacterial culture device comprises a culture bottle and a filter fiber, wherein both ends of the culture bottle and the filter fiber are connected via a liquid pipeline and a diaphragm pump to form a loop; the filter fiber is also connected to a waste liquid bucket via a liquid pipeline and a diaphragm pump to replace the culture liquid in the culture bottle; A magnetic stirrer is arranged inside the culture bottle, and an electromagnet is arranged at the bottom of the culture bottle to drive the magnetic stirrer to rotate; a waterproof and breathable membrane is arranged on the culture bottle to control the gas exchange between the culture bottle and the outside world; a plurality of sensors are arranged in the culture bottle to monitor the status information in the culture bottle.

[0020] When the filtering unit recovers the culture fluid transmitted by the culture bottle, the waste liquid recovery monitoring concentration threshold fluctuation interference quantity corresponding to the current time is generated in combination with the monitoring information of the bacterial culture equipment in the historical data. The acquisition method is as follows: Step 1, extract the culture solution concentrations monitored by the sensor at each time point in the time period between two adjacent waste liquid recovery operations in the historical data, and construct a culture solution concentration fluctuation data pair, recorded as (t, Ct), wherein t represents the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation; Ct represents the culture solution concentration value corresponding to the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation when t is the interval, and the value of Ct is equal to 10 to the reciprocal of the pH value corresponding to t. Step 2: connect the corresponding coordinate points of the culture solution concentration fluctuation data corresponding to each time point in the time period between any two adjacent waste liquid recovery operations in a plane rectangular coordinate system in sequence, and obtain a curve of the relationship between the culture solution concentration and time corresponding to the two adjacent waste liquid recovery operations, wherein the plane rectangular coordinate system is constructed with o as the origin, the interval time as the x-axis, and the culture solution concentration as the y-axis; Step 3: Mark the coordinate points with the largest culture solution concentration among the corresponding coordinate points of each change relationship curve when the horizontal coordinates in the plane rectangular coordinate system are the same, and fit the coordinate points of each mark in the plane rectangular coordinate system according to the preset function model y= to generate a reference function of the change relationship between the culture solution concentration and time corresponding to the current time, recorded as function (x); Step 4: Obtain the average value of the interval delay from each time the waste liquid recovery operation instruction is generated to the start of the corresponding waste liquid recovery operation instruction in the historical data, recorded as TD, and calculate the waste liquid recovery monitoring concentration threshold fluctuation interference corresponding to the current time, recorded as AF, AF=(r+1)·function(TE-TD), Wherein, TE represents the predicted value of the interval between the time point of the next waste liquid recovery operation instruction based on the current time and the time of the previous waste liquid recovery operation; the value of r is equal to the average value of the data fitting deviation corresponding to each time point in the time period from the previous waste liquid recovery operation time based on the current time to the current time; The data fitting deviation corresponding to any time point is recorded as M, then M=(Cs-Cp) / Cp, Cs represents the culture solution concentration actually monitored by the sensor at the corresponding time point; Cp represents the culture solution concentration corresponding to the corresponding time point in function (x); TE=function -1 (AR / (r+1)), Among them, AR represents the waste liquid recovery monitoring concentration threshold preset in the database; function -1 () represents the inverse function of function(); function -1(AR / (r+1)) represents the horizontal coordinate value corresponding to the culture medium concentration of function (x) being AR / (r+1); r represents the function fitting deviation coefficient; The filtering unit determines the generation condition of the waste liquid recovery operation instruction according to the waste liquid recovery monitoring concentration threshold fluctuation interference amount AF corresponding to the current time, When the sensor detects that the concentration of the culture fluid transferred from the culture bottle to the filter fiber before recovery is less than or equal to AF, it is determined to immediately generate a waste liquid recovery operation instruction; otherwise, the filter unit does not perform the recovery operation of the culture fluid transferred from the culture bottle; The waste liquid recovery operation instruction includes the waste liquid recovery time and the waste liquid recovery amount. The waste liquid recovery time is the time when the corresponding waste liquid recovery operation instruction is generated, and the waste liquid recovery amount is a threshold value set manually.

[0021] The culture liquid circuit unit is used to control the culture liquid circuit in the bacterial culture device; The culture fluid circuit unit includes a control module, a detection module and a liquid adding module. The control module is used to control the temperature and gas concentration in the culture bottle; The detection module is used to detect the liquid level and pH value of the culture solution in the culture bottle; the liquid level is monitored and acquired by a liquid level sensor built into the culture bottle, and the pH value is detected and controlled by adding a preset indicator and by a color sensor through a color change. The liquid adding module is used to control the type and amount of solution added into the culture bottle.

[0022] The liquid adding module controls the type of solution added to the culture bottle to be the same as the type of culture medium solution selected when initially culturing bacteria in the current culture bottle; When the liquid adding module controls the amount of solution added to the culture bottle, the corresponding liquid adding operation instruction includes the liquid adding operation time and the liquid adding amount; the liquid adding operation time is the time point corresponding to when the liquid level height fluctuation value monitored by the sensor in the most recent unit time is less than or equal to the preset fluctuation value and the absolute value of the difference between the corresponding liquid level height and the preset liquid level height is less than or equal to the preset liquid level deviation; The liquid addition amount is the volume of culture liquid corresponding to the liquid level height difference between the liquid level height corresponding to the corresponding liquid addition operation time and the liquid level height preset value; The unit time is a constant preset in the database; the liquid level height fluctuation value is equal to the difference between the maximum liquid level height and the minimum liquid level height in the corresponding time period.

[0023] The sampling unit is used to control the sampling operation of the culture solution in the culture solution path of the bacteria culture device.

[0024] The sampling unit performs a sampling operation on the culture solution at a preset time interval, and the amount of each sampling is preset.

[0025] This embodiment includes the following preparations before testing: Determine the test plan: After inquiry, cefuroxime is a time-dependent antibacterial drug, and the clinical practice usually adopts a medication plan of multiple administrations within a day. The test is set to be administered every eight hours, and each supplementary administration is completed within 15 minutes. The total test time is 48 hours. The strain selected is Staphylococcus aureus ATCC 29213; Test the MIC (minimum inhibitory concentration) of antibiotics against the strains to be tested, prepare fresh culture medium, stock solution of antimicrobial drugs, and bacterial suspension; Test the MIC of antibiotics against the strain to be tested: Inoculate the test strain ATCC 29213 into the culture medium plate, and grow colonies after 18-24 hours for later use; prepare physiological saline (or phosphate buffer, etc.) and dispense into turbidimetric tubes, each containing 9 mL, and sterilize (sterilize at 121°C for 15-30 min); add a certain amount of bacteria into the turbidimetric tube to make a bacterial suspension, and adjust the McFarland turbidity to 0.5-1 McFarland; according to the CLSI standard operation and the E-test usage guide, dip the bacterial suspension with a swab, apply it on the culture medium, dry it for 15-20 minutes, stick the cefuroxime E-test paper strip on the surface of the bacterial lawn, culture it overnight, and read the scale based on the edge of the inhibition zone and the intersection of the test strip, which is the MIC value of ATCC 29213 against cefuroxime is 2ug / mL; Prepare fresh culture medium: Use MH broth as culture medium, dissolve 21 g of MH broth powder (Sigma) in 1 L of distilled water, sterilize by autoclaving at 121°C for 15 min, and cool before use; Preparation of antibacterial stock solution: Use cefuroxime sodium for injection (1.5g / bottle) to prepare, take 150mL of normal saline, dissolve one bottle of medicine, then the concentration of cefuroxime is 10mg / mL; set aside the prepared antibacterial stock solution; Preparation of bacterial suspension: physiological saline (or phosphate buffer, etc.) is dispensed into test tubes, each containing 9 mL, and sterilized (sterilized at 121°C for 15-30 min); the sterilized test tubes containing 9 mL of physiological saline are numbered 1, 2, 3, 4, 5, 6, 7, and 8. A certain amount of bacteria is added to the test tube numbered 1, mixed with a vortex oscillator, and the McFarland turbidity is adjusted to 0.5 McFarland to prepare the first dilution gradient bacterial suspension, with a bacterial volume of approximately 1.5×108 CFU / mL; 1 mL of the first gradient bacterial suspension is drawn into the test tube numbered 2, mixed evenly, and the second dilution bacterial suspension is obtained, and so on.

[0026] The program of the device is set through the host computer unit and the central control device. The parameters mainly include: running time, temperature control, atmosphere control, volume of culture medium in the culture bottle, power (i.e. flow rate) of multiple peristaltic pumps, pH value detection, time interval for updating culture medium / drug solution and other threshold conditions, sample storage area temperature, sampling volume and frequency, etc.; Dynamic regulation of bacterial culture environment: Running time: 48 hours; Temperature setting: 35~37℃; Atmosphere control: According to the suitable environment for the growth of Staphylococcus aureus, the atmosphere is set to air; The volume of culture medium in the culture bottle: set to 200mL. There is a liquid level sensor in the culture bottle. According to the signal of the sensor, the central control unit can calculate the liquid volume in the culture bottle. Multiple peristaltic pump power (i.e. flow rate): set to 30mL / min; pH value: After inquiry, the suitable pH value for Staphylococcus aureus culture is 7.2~7.4, and the boundary values ​​are set at 6.5 and 8.5. If the pH reaches the boundary value, the pH value adjustment is started; Time interval for updating drug solution: After inquiry, the recommended interval for clinical intravenous infusion of cefuroxime is 8 hours, so the time is set to 8 hours; Renewal of the volume of culture medium: The culture medium replacement threshold (waste recovery volume) is 40 mL; and the culture medium replacement time is dynamically controlled; Sample storage area temperature: 4°C; Sampling frequency and volume: The sampling frequency was set to 90 min, with 2 mL sampled each time.

[0027] After the settings are completed, wait for 30 to 60 minutes to allow the system to warm up.

[0028] Testing process: According to the pre-set running time program, the central control device will stop the test 48 hours after the set stop time; According to the pre-set temperature parameters, the central control device controls the power of the Peltier to maintain the temperature of the culture bottle at the pre-set temperature of 35~37℃, with an error of no more than ±2℃; According to the preset atmosphere parameters, the central control device controls the air inlet valve to keep the atmosphere above the culture bottle at the preset air atmosphere; According to the pre-set peristaltic pump power, the central control device will control the peristaltic pump to provide power for the flow of liquid in the system according to the pre-set power and flow rate during the set time period; According to the pre-set pH threshold, if the pH in the culture bottle reaches the boundary value, the pH adjustment is initiated by renewing the culture medium; During the test, the culture medium will be updated through the central control device. According to the pre-set volume of the updated culture medium solution of 40mL, the central control device will discharge 40mL of culture medium into the waste liquid bucket and inject fresh drug-containing culture medium into the culture bottle. The signal fed back by the liquid level sensor can be used to judge the liquid level.

[0029] According to the sampling frequency and volume set in advance, the sampling system will take samples every 90 minutes. The sampling volume is 2mL and stored in the sample storage area at 4°C. Users can perform further analysis on the samples, such as drug concentration analysis, inoculation culture to see the bacterial count, flow analysis, etc.

[0030] Test completed: According to the analysis results in the previous step, the PD parameters can be obtained.

[0031] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0032] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An intelligent monitoring system for bacterial culture equipment based on big data, characterized in that: The system comprises: A host computer unit, the host computer unit is used to generate and issue control instructions; The central control unit is used to receive control instructions issued by the host computer unit, control the execution unit to complete each control instruction, receive feedback from the sensor bound to the execution unit, generate operation status data corresponding to the execution unit, and feed it back to the host computer unit; The execution unit includes a culture fluid path unit, a filtering unit and a sampling unit. The culture liquid circuit unit is used to control the culture liquid circuit in the bacterial culture device; The filtering unit controls the filtering fiber in the bacterial culture device to recover or filter the culture solution transmitted by the culture bottle in the culture solution path, the filtered solution flows back into the culture bottle, and the recovered solution flows into the waste liquid barrel through the peristaltic pump; The sampling unit is used to control the sampling operation of the culture solution in the culture solution path of the bacteria culture device.

2. According to claim 1, a big data-based intelligent monitoring system for bacterial culture equipment is characterized by: The bacterial culture device comprises a culture bottle and a filter fiber, wherein both ends of the culture bottle and the filter fiber are connected via a liquid pipeline and a diaphragm pump to form a loop; the filter fiber is also connected to a waste liquid bucket via a liquid pipeline and a diaphragm pump to replace the culture liquid in the culture bottle; A magnetic stirrer is arranged inside the culture bottle, and an electromagnet is arranged at the bottom of the culture bottle to drive the magnetic stirrer to rotate; a waterproof and breathable membrane is arranged on the culture bottle to control the gas exchange between the culture bottle and the outside world; a plurality of sensors are arranged in the culture bottle to monitor the status information in the culture bottle.

3. According to claim 1, a big data-based intelligent monitoring system for bacterial culture equipment is characterized by: The culture fluid circuit unit includes a control module, a detection module and a liquid adding module. The control module is used to control the temperature and gas concentration in the culture bottle; The detection module is used to detect the liquid level and pH value of the culture solution in the culture bottle; the liquid level is monitored and acquired by a liquid level sensor built into the culture bottle, and the pH value is detected and controlled by adding a preset indicator and by a color sensor through a color change. The liquid adding module is used to control the type and amount of solution added into the culture bottle.

4. According to claim 1, a big data-based intelligent monitoring system for bacterial culture equipment is characterized by: When the filtering unit recovers the culture fluid transmitted by the culture bottle, the waste liquid recovery monitoring concentration threshold fluctuation interference quantity corresponding to the current time is generated in combination with the monitoring information of the bacterial culture equipment in the historical data. The acquisition method is as follows: Step 1, extract the culture solution concentrations monitored by the sensor at each time point in the time period between two adjacent waste liquid recovery operations in the historical data, and construct a culture solution concentration fluctuation data pair, recorded as (t, Ct), wherein t represents the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation; Ct represents the culture solution concentration value corresponding to the interval between the time period between two adjacent waste liquid recovery operations and the time point of the previous waste liquid recovery operation when t is the interval, and the value of Ct is equal to 10 to the reciprocal of the pH value corresponding to t. Step 2: connect the corresponding coordinate points of the culture solution concentration fluctuation data corresponding to each time point in the time period between any two adjacent waste liquid recovery operations in a plane rectangular coordinate system in sequence, and obtain a curve of the relationship between the culture solution concentration and time corresponding to the two adjacent waste liquid recovery operations, wherein the plane rectangular coordinate system is constructed with o as the origin, the interval time as the x-axis, and the culture solution concentration as the y-axis; Step 3: Mark the coordinate points with the largest culture solution concentration among the corresponding coordinate points of each change relationship curve when the horizontal coordinates in the plane rectangular coordinate system are the same, and fit the coordinate points of each mark in the plane rectangular coordinate system according to the preset function model y= to generate a reference function of the change relationship between the culture solution concentration and time corresponding to the current time, recorded as function (x); Step 4: Obtain the average value of the interval delay from each time the waste liquid recovery operation instruction is generated to the start of the corresponding waste liquid recovery operation instruction in the historical data, recorded as TD, and calculate the waste liquid recovery monitoring concentration threshold fluctuation interference corresponding to the current time, recorded as AF, AF=(r+1)·function(TE-TD), Wherein, TE represents the predicted value of the interval between the time point of the next waste liquid recovery operation instruction based on the current time and the time of the previous waste liquid recovery operation; the value of r is equal to the average value of the data fitting deviation corresponding to each time point in the time period from the previous waste liquid recovery operation time based on the current time to the current time; The data fitting deviation corresponding to any time point is recorded as M, then M=(Cs-Cp) / Cp, Cs represents the culture solution concentration actually monitored by the sensor at the corresponding time point; Cp represents the culture solution concentration corresponding to the corresponding time point in function (x); TE=function -1 (AR / (r+1)), Among them, AR represents the waste liquid recovery monitoring concentration threshold preset in the database; function -1 () represents the inverse function of function(); function -1 (AR / (r+1)) represents the horizontal coordinate value corresponding to the culture medium concentration of function (x) being AR / (r+1); r represents the function fitting deviation coefficient; The filtering unit determines the generation condition of the waste liquid recovery operation instruction according to the waste liquid recovery monitoring concentration threshold fluctuation interference amount AF corresponding to the current time, When the sensor detects that the concentration of the culture fluid transferred from the culture bottle to the filter fiber before recovery is less than or equal to AF, it is determined to immediately generate a waste liquid recovery operation instruction; otherwise, the filter unit does not perform the recovery operation of the culture fluid transferred from the culture bottle; The waste liquid recovery operation instruction includes the waste liquid recovery time and the waste liquid recovery amount. The waste liquid recovery time is the time when the corresponding waste liquid recovery operation instruction is generated, and the waste liquid recovery amount is a threshold value set manually.

5. According to claim 4, a big data-based intelligent monitoring system for bacterial culture equipment is characterized in that: The liquid adding module controls the type of solution added to the culture bottle to be the same as the type of culture medium solution selected when initially culturing bacteria in the current culture bottle; When the liquid adding module controls the amount of solution added to the culture bottle, the corresponding liquid adding operation instruction includes the liquid adding operation time and the liquid adding amount; the liquid adding operation time is the time point corresponding to when the liquid level height fluctuation value monitored by the sensor in the most recent unit time is less than or equal to the preset fluctuation value and the absolute value of the difference between the corresponding liquid level height and the preset liquid level height is less than or equal to the preset liquid level deviation; The liquid addition amount is the volume of culture liquid corresponding to the liquid level height difference between the liquid level height corresponding to the corresponding liquid addition operation time and the liquid level height preset value; The unit time is a constant preset in the database; the liquid level height fluctuation value is equal to the difference between the maximum liquid level height and the minimum liquid level height in the corresponding time period.

6. The intelligent monitoring system for bacterial culture equipment based on big data according to claim 5 is characterized in that: The sampling unit performs a sampling operation on the culture solution at a preset time interval, and the amount of each sampling is preset.

7. A method for intelligent monitoring of bacterial culture equipment based on big data, characterized in that: The method comprises the following steps: S1. Setting the operating parameters of the bacterial culture equipment through the host computer unit and the central control unit; S2. Receive feedback data from the sensor bound to the execution unit corresponding to the bacterial culture equipment through the central control unit, generate running status data corresponding to the execution unit, and feed it back to the host computer unit; S3. According to the operation status data of the execution unit fed back by the central control unit and the operation parameter setting result corresponding to the bacterial culture equipment, the host computer unit generates a control instruction corresponding to the execution unit, and controls the execution unit through the central control unit; The control instructions include instructions for controlling the recovery of waste liquid, instructions for controlling the collection operation of culture liquid, instructions for controlling the environmental temperature in the culture bottle, instructions for controlling the environmental atmosphere in the culture bottle, instructions for controlling the renewal of culture medium and instructions for controlling the environmental temperature of sample storage.

8. The method for intelligent monitoring of bacterial culture equipment based on big data according to claim 7, characterized in that: The operating parameters include the operating time of the culture fluid circuit unit in the execution unit, the ambient temperature in the culture bottle, the ambient atmosphere, the culture medium volume, the pH value, the culture medium renewal judgment conditions, the waste liquid recovery conditions in the filtration unit, the single recovery volume of the waste liquid, and the sample storage temperature, sampling volume and sampling frequency in the sampling unit.