Isolator operation state monitoring method and system

Abstract

The invention relates to the technical field of isolator monitoring, and relates to an isolator operation state monitoring method and system, and the method comprises the steps: obtaining the temperature and internal pressure difference of an isolator at a current moment, and calculating an environment stability index; obtaining the oxygen concentration and the pH adjusting gas concentration of each moment in the isolator in a preset time period; calculating experiment effect indexes; and taking a mean value of the environment stability index and the experiment effect index as a target index, and giving an alarm when the target index is smaller than a preset threshold value. According to the present invention, by determining whether the sterile experiment at the current moment is in the environment at the current moment to possibly cause the poor quality of the sterile experiment, the early warning is given out before the potential risk occurs, and the error caused by the single environmental factor monitoring is reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of isolator monitoring, and more specifically, to a method and system for monitoring the operating status of an isolator. Background Art

[0002] The isolator (or sterile isolator) uses sterile isolation technology to create a highly clean, continuously effective operating space. It can minimize the contamination of microorganisms and various particles, thereby improving the accuracy of sterility testing. The main function of the sterile isolator is to isolate microorganisms, dust and other sources of contamination in the external environment to ensure the sterility of the internal environment and the reliability of the experiment or production process. The working principle of the sterile isolator is generally to prevent external contaminants from entering through efficient filtration of the air inside the isolator, continuous negative pressure control or other technical means, while also ensuring that the airflow, temperature, humidity and other factors of the internal environment meet specific requirements. It usually includes a sealed operating space equipped with a high-efficiency air filtration system (such as a HEPA filter), as well as an airflow and pressure differential control system to monitor and regulate air flow and environmental stability during the experiment or production process. There are two simple purposes for using it. One is to protect the sample from contamination from the environment, which includes contamination from the operator and the inspection environment. The second is to protect the operator from contamination by toxic and hazardous substances.

[0003] In order to ensure the smooth progress of sterile experiments, isolators usually require a stable airflow system. In the prior art, it is usually determined whether an alarm is needed based on the pressure difference between the air inlet pressure and the air outlet pressure of the isolator's soft bag. For example, a Chinese patent document with publication number CN205922400U discloses a pressure differential alarm device for an experimental animal sterile isolator. The patent document monitors the pressure in the isolator soft bag. When the pressure of the isolator soft bag is not within the range set by the micro-pressure differential switch, an alarm is issued to ensure the quality of the experiment.

[0004] However, the pressure difference at the current moment directly reflects the stability of the airflow in the isolator cabin, and thus indirectly reflects the quality of the experiment. Therefore, judging whether an early warning is needed to ensure the quality of the sterile experiment based on the pressure difference in the isolator cabin may not be accurate enough. Summary of the invention

[0005] In order to solve the above-mentioned technical problem that the judgment based on the pressure difference of the isolator cabin whether an early warning is needed to ensure the quality of the sterile experiment may not be accurate enough, the present invention provides solutions in the following aspects.

[0006] In a first aspect, a method for monitoring the operating status of an isolator is provided, the method comprising: obtaining the temperature and internal pressure difference of the isolator at a current moment; calculating an environmental stability index α : .

[0007] in, k 1 is the first standard value of the preset size, k 2 is the second standard value of the preset size, T is the temperature at the current moment, P is the pressure difference at the current moment, and the exp function is an exponential function with the real number e as the base; the oxygen concentration and the pH adjustment gas concentration inside the isolator at each moment in a predetermined time period are obtained, wherein the last moment of the predetermined time period is the current moment; the experimental effect index is calculated, wherein the difference between the oxygen concentration and the third standard value is the first difference, the difference between the pH adjustment gas concentration and the fourth standard value is the second difference, the experimental effect index is inversely proportional to the absolute value of the first difference at each moment, the experimental effect index is inversely proportional to the absolute value of the second difference at each moment, and the first standard value and the second standard value are both values ​​of preset sizes; the average of the environmental stability index and the experimental effect index is the target index, and an alarm is issued in response to the target index being less than the preset threshold.

[0008] The beneficial effects of the present invention are as follows: the present invention obtains the quality of the sterile experiment at the current moment, i.e., the experimental effect index, by measuring the difference between the actual gas concentration and the ideal gas concentration during the sterile experiment. The present invention also obtains the environmental quality of the sterile experiment, i.e., the environmental stability index, based on the environmental temperature and pressure difference of the sterile experiment at the current moment (i.e., the temperature of the isolator at the current moment and the internal pressure difference), and then determines whether an alarm is needed based on the quality of the sterile experiment and its environmental quality. Based on this, the present invention determines whether the sterile experiment at the current moment is in the environment at the current moment and whether it may cause the sterile experiment to have poor quality, and then issues an early warning before the potential risk occurs, while also reducing the error caused by monitoring a single environmental factor.

[0009] Preferably, the formula for calculating the experimental effect index is: .

[0010] in is the experimental effect indicator, n is the number of moments in the predetermined time period, i is a positive integer, k 3 is the third standard value, k 4 is the fourth standard value, For the i The oxygen concentration at the time, For the i pH adjustment gas concentration at the moment, is the first weight, is the second weight.

[0011] Preferably, calculating the first weight and the second weight includes: fitting the first difference at each moment in a predetermined time period to obtain a first curve; fitting the second difference at each moment in a predetermined time period to obtain a second curve; fitting the pressure difference inside the isolator at each moment in a preset time period to obtain a third curve; calculating the Euclidean distance between the first curve and the third curve, recorded as the first difference degree A 1 ; Calculate the Euclidean distance between the second curve and the third curve, recorded as the second difference degree A 2 ; Calculate the first weight and the second weight ,in , .

[0012] The present invention can reduce the noise in the data corresponding to the first difference (i.e., the oxygen concentration at each moment), reduce the noise in the data corresponding to the second difference (i.e., the pH adjustment gas concentration at each moment), and reduce the noise in the pressure difference data (the pressure difference at each moment) by fitting the first difference, the second difference, and the pressure difference at each moment and then calculating the difference between the first difference and the pressure difference (the first difference degree) and the difference between the second difference and the pressure difference (the second difference degree), so that the difference between the subsequent first curve and the third curve can more accurately reflect the difference between the data corresponding to the first difference and the pressure difference data, and also can more accurately reflect the difference between the data corresponding to the second difference and the pressure difference data.

[0013] Preferably, the first difference, the second difference or the pressure difference at each moment in a predetermined time period is fitted by a polynomial fitting algorithm, wherein the maximum order of the polynomial functions corresponding to the first curve, the second curve and the third curve is the same.

[0014] The polynomial fitting algorithm used in the present invention can provide higher fitting accuracy, and the obtained curve can better reflect the change trend of the first difference, the second difference or the pressure difference.

[0015] Preferably, the first difference degree is calculated A 1 The formula is: .

[0016] in, The first curve j The value of the moment, The third curve j The value of the moment, m , j Is a positive integer.

[0017] The present invention can accurately measure the difference between the two curves at each moment by calculating the square of the difference between the first curve and the third curve at each moment, summing the square of the difference at each moment and then taking the square root to obtain the Euclidean distance between the two curves.

[0018] Preferably, the second difference degree is calculated A 2 The formula is: .

[0019] in, The second curve j The value of the moment, The third curve j The value of the moment, m , j Is a positive integer.

[0020] Preferably, a method for monitoring the operating status of an isolator further comprises collecting the vibration frequency of the isolator at the current moment before obtaining the target index. L , the environmental stability index is corrected, and the mean value between the corrected environmental stability index and the experimental effect index is determined as the target index, wherein the formula for correcting the environmental stability index is: ,in, is the revised environmental stability index, w Preset size correction parameter, 0< w <1, norm is the standard normalization function.

[0021] The present invention corrects the environmental stability index by using the vibration frequency of the isolator at the current moment, thereby providing a more reliable and accurate evaluation standard for the experiment.

[0022] Preferably, the correction parameter w The value of is 0.5.

[0023] In a second aspect, an isolator operation status monitoring system is provided, comprising a processor and a memory, wherein the memory stores a computer program, and the processor executes the computer program to implement an isolator operation status monitoring method as described in any one of the above invention contents.

[0024] The beneficial effects of the present invention are: The present invention obtains the experimental quality at the current moment (i.e., the experimental effect index) by calculating the difference between the gas concentration and the ideal concentration during the sterile experiment. At the same time, the environmental quality (i.e., the environmental stability index) is obtained by combining the ambient temperature and pressure difference of the sterile experiment (the current temperature and internal pressure difference of the isolator). Through these two indicators, it is possible to determine whether an alarm needs to be issued and identify the potential risk of poor experimental quality in advance. In addition, the present invention reduces the errors that may be caused by monitoring a single environmental factor (i.e., the errors caused by the pressure difference judgment based on the isolator cabin) and provides a more accurate early warning. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The above and other objects, features and advantages of the exemplary embodiments of the present invention will become readily understood by reading the detailed description below with reference to the accompanying drawings. In the accompanying drawings, several embodiments of the present invention are shown in an exemplary and non-limiting manner, and the same or corresponding reference numerals represent the same or corresponding parts, wherein: Figure 1 is a flowchart of a method for monitoring the operating status of an isolator according to an embodiment of the present invention; Figure 2 It is a structural block diagram of an isolator operation status monitoring system according to an embodiment of the present invention. DETAILED DESCRIPTION

[0026] 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 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 those skilled in the art without creative work are within the scope of protection of the present invention.

[0027] The specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0028] Figure 1 The present invention is a flowchart of a method for monitoring the operating status of an isolator according to an embodiment of the present invention.

[0029] like Figure 1 As shown, a method for monitoring the operating status of an isolator includes steps S1 to S4.

[0030] Step S1: Obtain the temperature and internal pressure difference of the isolator at the current moment, and calculate the environmental stability index.

[0031] Among them, the calculated environmental stability index α The formula is: . k 1 is the first standard value of the preset size, k2 is the second standard value of the preset size, T is the temperature at the current moment, P is the pressure difference at the current moment, and the exp function is an exponential function with the real number e as the base.

[0032] Among them, the first standard value k 1 The temperature of the experimental environment (i.e., the isolator cabin) expected for sterile experiments; the second standard value k 2 The pressure difference inside the isolator (i.e., inside the isolator cabin) expected for the sterile experiment. The difference in wind pressure between the isolator's air inlet and outlet is the pressure difference inside the isolator. In actual use, the pressure difference can be changed by adjusting the operating state of the fan or the opening of the inlet and outlet. The change in pressure difference will affect the flow rate and exhaust efficiency of the gas in the isolator cabin, and then affect the gas concentration in the cabin. Based on this, the instability of the pressure difference will lead to uneven exhaust volume, thereby affecting the change in gas concentration.

[0033] It should be noted that The larger the value is, the greater the difference between the temperature in the isolator and the expected temperature of the sterile experiment (which is usually the set value of the temperature in the isolator), which reflects that the working condition of the isolator is worse and the environment in the isolator is more unstable. The larger the pressure difference is, the greater the difference between the pressure difference in the isolator cabin and the expected pressure difference in the sterile experiment (this pressure difference is usually also the set value of the pressure difference in the isolator cabin), which reflects that the working condition of the isolator is worse at this time and the environment in the isolator cabin is more unstable. or The larger the environmental stability index α The smaller the environmental stability index α The larger the value, the better the isolator's working condition is and the more stable the environment inside the isolator cabin is.

[0034] Step S2: Obtaining the oxygen concentration and pH adjustment gas concentration inside the isolator at each time within a predetermined time period.

[0035] The last moment of the scheduled time period is the current moment.

[0036] In one embodiment, the pH adjusting gas is ammonia or carbon dioxide. It should be noted that different sterile experiments may have higher precision requirements for the concentration of one or more specific gases to meet the requirements for the experimental environment. For example, some cell culture experiments need to be carried out within a specific pH range to ensure the growth and reproduction of cells, so the pH value of the environment in the isolator cabin is adjusted by ammonia to keep the culture solution within the alkaline range, or the pH value of the environment in the isolator cabin is adjusted by carbon dioxide to keep the culture solution within the acidic range. Based on this, the present invention can determine that the pH adjusting gas is ammonia or carbon dioxide according to the requirements of the sterile experiment.

[0037] Step S3: Calculate the experimental effect index.

[0038] The experimental effect index is inversely proportional to the absolute value of the first difference at each moment, and the experimental effect index is inversely proportional to the absolute value of the second difference at each moment. The first standard value and the second standard value are both preset values.

[0039] In one embodiment, the experimental effect index is calculated β The formula is: .

[0040] in is the experimental effect indicator, n is the number of moments in the predetermined time period, i is a positive integer, k 3 is the third standard value, k 4 is the fourth standard value, For the i The oxygen concentration at the time, For the i pH adjustment gas concentration at the moment, is the first weight, is the second weight.

[0041] It should be noted that the third standard value k 3 The oxygen concentration of the experimental environment expected for sterility experiments; k 4 The fourth standard value is the concentration of the pH-adjusting gas in the experimental environment desired for the sterility experiment. It reflects the difference in oxygen concentration between the actual environment of the sterile experiment and the expected environment (i.e. the most ideal experimental environment) within a predetermined period of time. The larger the difference is, the worse the effect of the sterility test is. It reflects the difference between the pH adjustment concentration between the actual environment of the sterility experiment and the expected environment (i.e. the most ideal experimental environment) within a predetermined time period. The larger the value, the greater the difference, and the worse the effect of the sterility test. or The larger the experimental effect index β The smaller the experimental effect is. β The larger it is, the more stable the environment is during the sterile experiment and the better the experimental effect is.

[0042] In one embodiment, the first weight The experience value is 0.6, the second weight The experience value is 0.4.

[0043] In another embodiment, calculating the first weight and the second weight includes: taking the difference between the oxygen concentration and the third standard value as the first difference, and the difference between the pH adjustment gas concentration and the fourth standard value as the second difference, fitting the first difference at each moment in the predetermined time period to obtain a first curve; fitting the second difference at each moment in the predetermined time period to obtain a second curve; fitting the pressure difference inside the isolator at each moment in the preset time period to obtain a third curve; calculating the Euclidean distance between the first curve and the third curve, recorded as the first difference degree A 1 ; Calculate the Euclidean distance between the second curve and the third curve, recorded as the second difference degree A 2 ; Calculate the first weight and the second weight ,in , .

[0044] Among them, Euclidean distance is a commonly used method to measure the distance between two points, which is derived from Euclidean geometry. It represents the straight-line distance between two points in space. Euclidean distance is often used to measure the similarity between data points in cluster analysis and nearest neighbor algorithms.

[0045] It should be noted that fitting the first difference, the second difference or the pressure difference can smooth the data (the first difference, the second difference and the pressure difference), remove high-frequency noise, and extract the main trend or law of the data.

[0046] In one embodiment, the first difference, the second difference or the pressure difference at each moment in a predetermined time period is fitted by a polynomial fitting algorithm, wherein the maximum order of the polynomial functions corresponding to the first curve, the second curve and the third curve is the same.

[0047] Furthermore, considering that the gas in the isolator cabin is always in a flowing state, the collected gas concentration data cannot fully and accurately reflect the average concentration of the gas in the isolator cabin. Also, when the rate of delivering oxygen and pH adjusting gas to the isolator cabin does not change, it is mainly the pressure difference that causes the concentration of oxygen and pH adjusting gas to change. Therefore, the smaller the difference between the concentration change of oxygen or pH adjusting gas and the change of pressure difference, the more accurately the concentration data change of oxygen or pH adjusting gas can reflect the actual average concentration of the gas in the isolator cabin.

[0048] Based on this, the first degree of difference A 1 The smaller the value, the more similar the change in oxygen concentration is to the change in pressure difference. At this time, the data of the change in oxygen concentration is more reliable, thus reflecting the difference in oxygen concentration between the actual environment of the sterile experiment and the expected environment (i.e., the most ideal experimental environment). The corresponding first weight Similarly, the second difference degree A 2 The smaller the value, the more similar the change in pH-adjusting gas concentration is to the change in pressure difference. At this time, the data of oxygen concentration change is more reliable. Therefore, it reflects the difference between the pH-adjusting gas concentration between the actual environment of the sterile experiment and the expected environment (i.e., the most ideal experimental environment). The corresponding second weight The bigger.

[0049] In one embodiment, the first difference degree is calculated A 1 The formula is: .

[0050] in, The first curve j The value of the moment, The third curve j The value of the moment, m , j Is a positive integer.

[0051] In one embodiment, the second difference degree is calculated A 2 The formula is: .

[0052] in, The second curve j The value of the moment, The third curve j The value of the moment, m , jIs a positive integer.

[0053] Step S4: Taking the average of the environmental stability index and the experimental effect index as the target index, in response to the target index being less than a preset threshold, an alarm is issued.

[0054] It should be noted that due to the environmental stability index α The larger the value, the better the isolator's working condition and the more stable the environment inside the isolator. β The larger the value, the more stable the environment during the sterile experiment and the better the experimental effect. It can be understood that the environmental stability index reflects the stability of the environment in which the sterile experiment is located at the current moment, and the experimental effect index β It reflects the stability of the sterile experiment effect at the current moment. Therefore, the mean of the environmental stability index and the experimental effect index (i.e., the target index) reflects the prediction of the sterile experiment effect at the current moment, that is, whether the stability of the sterile experiment effect at the current moment in the environment at the current moment may lead to poor experimental results. Therefore, when the experimental result is predicted to be poor at the current moment, that is, when the target index is small, an alarm is issued to enable the experimenter to check the isolator to improve the environment inside the isolator to ensure the quality of the experimental results.

[0055] Furthermore, the present invention also includes collecting the vibration frequency L of the isolator at the current moment before obtaining the target index, correcting the environmental stability index, and determining the mean value between the corrected environmental stability index and the experimental effect index as the target index, wherein the formula for correcting the environmental stability index is: ,in, is the revised environmental stability index, w Preset size correction parameter, 1< w <2, norm is the standard normalization function. Among them, the standard normalization function norm The vibration frequency L Mapped to a value between 0 and 1.

[0056] It should be noted that the greater the vibration frequency of the isolator at the current moment, the more likely it is that a gap will appear in the sterile isolator cabin, causing unfiltered gas from outside the cabin to enter, resulting in deviations in the experimental results. Therefore, the greater the vibration frequency at the current moment, the more unstable the operating condition of the isolator at the current moment.

[0057] In one embodiment, the correction parameter w The value of is 0.5. norm ( L ) is equal to 0.5, then the revised environmental stability index is equal to the environmental stability index before the revision; if norm ( L) is greater than 0.5, the revised environmental stability index is less than the environmental stability index before the revision; if norm ( L ) is less than 0.5, the corrected environmental stability index is greater than the environmental stability index before correction.

[0058] Figure 2 FIG. 4 is a block diagram schematically showing a structure of an isolator operation status monitoring system according to this embodiment.

[0059] The present invention also provides an isolator operation status monitoring system. Figure 2 As shown, the system includes a processor and a memory, wherein the memory stores computer program instructions, and when the computer program instructions are executed by the processor, an isolator operating status monitoring method according to the first aspect of the present invention is implemented.

[0060] In the present invention, the aforementioned memory may be any tangible medium containing or storing a program, which may be used by or in combination with an instruction execution system, apparatus or device. For example, a computer-readable storage medium may be any appropriate magnetic storage medium or magneto-optical storage medium, such as a resistive random access memory RRAM (Resistive Random Access Memory), a dynamic random access memory DRAM (Dynamic Random Access Memory), a static random access memory SRAM (Static Random-Access Memory), an enhanced dynamic random access memory EDRAM (Enhanced Dynamic Random Access Memory), a high-bandwidth memory HBM (High-Bandwidth Memory), a hybrid memory cube HMC (Hybrid Memory Cube), etc., or any other medium that can be used to store the required information and can be accessed by an application, a module, or both. Any such computer storage medium may be part of a device or accessible or connectable to a device. Any application or module described in the present invention may be implemented by computer-readable / executable instructions stored or otherwise maintained by such a computer-readable medium.

[0061] In the description of this specification, "plurality" or "several" means at least two, such as two, three or more, etc., unless otherwise clearly and specifically defined.

[0062] Although this specification has shown and described a number of embodiments of the present invention, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Those skilled in the art will conceive of many modifications, changes and alternatives without departing from the ideas and spirit of the present invention. It should be understood that in the practice of the present invention, various alternatives to the embodiments of the present invention described herein may be employed.

Claims

1. A method for monitoring the operating status of an isolator, characterized in that: include: Obtain the current temperature and internal pressure difference of the isolator and calculate the environmental stability index α : ； in, k 1 is the first standard value of the preset size, k 2 is the second standard value of the preset size, T is the temperature at the current moment, P is the pressure difference at the current moment, and the exp function is an exponential function with the real number e as the base; Obtaining the oxygen concentration and pH adjustment gas concentration inside the isolator at each moment in a predetermined time period, wherein the last moment of the predetermined time period is the current moment; Calculate the experimental effect index, wherein the difference between the oxygen concentration and the third standard value is the first difference, the difference between the pH adjustment gas concentration and the fourth standard value is the second difference, the experimental effect index is inversely proportional to the absolute value of the first difference at each moment, the experimental effect index is inversely proportional to the absolute value of the second difference at each moment, and the first standard value and the second standard value are both preset values; The average of the environmental stability index and the experimental effect index is taken as the target index. In response to the target index being less than a preset threshold, an alarm is issued.

2. The method for monitoring the operating status of an isolator according to claim 1, characterized in that: The formula for calculating the experimental effect index is: ,in is the experimental effect indicator, n is the number of moments in the predetermined time period, i is a positive integer, k 3 is the third standard value, k 4 is the fourth standard value, For the i The oxygen concentration at the time, For the i pH adjustment gas concentration at the moment, is the first weight, is the second weight.

3. A method for monitoring the operating status of an isolator according to claim 2, characterized in that: Calculating the first weight and the second weight includes: Fitting the first difference at each moment in a predetermined time period to obtain a first curve; Fitting the second difference at each moment in a predetermined time period to obtain a second curve; Fitting the pressure difference inside the isolator at each moment within a preset time period to obtain a third curve; Calculate the Euclidean distance between the first curve and the third curve, recorded as the first difference degree A 1; Calculate the Euclidean distance between the second curve and the third curve, recorded as the second difference degree A 2; Calculate the first weight and the second weight ,in , .

4. The method for monitoring the operating status of an isolator according to claim 3, characterized in that: The first difference, the second difference or the pressure difference at each moment in a predetermined time period is fitted by a polynomial fitting algorithm, wherein the maximum order of the polynomial functions corresponding to the first curve, the second curve and the third curve is the same.

5. The method for monitoring the operating status of an isolator according to claim 4, characterized in that: Calculate the first difference degree A The formula for 1 is: ； in, The first curve j The value of the moment, The third curve j The value of the moment, m , j Is a positive integer.

6. The method for monitoring the operating status of an isolator according to claim 4, characterized in that: Calculate the second difference degree A The formula for 2 is: ； in, The second curve j The value of the moment, The third curve j The value of the moment, m , j Is a positive integer.

7. The method for monitoring the operating status of an isolator according to claim 1, characterized in that: It also includes collecting the vibration frequency L of the isolator at the current moment before obtaining the target index, correcting the environmental stability index, and determining the mean value between the corrected environmental stability index and the experimental effect index as the target index, wherein the formula for correcting the environmental stability index is: ,in, is the revised environmental stability index, w Preset size correction parameter, 0< w <1, norm is the standard normalization function.

8. The method for monitoring the operating status of an isolator according to claim 1, characterized in that: Correction parameters w The value of is 0.

5.

9. An isolator operation status monitoring system, comprising a processor and a memory, wherein the memory stores a computer program, characterized in that: The processor executes the computer program to implement an isolator operating status monitoring method as described in any one of claims 1-8.

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