CN118090321A - Automatic sampling system, method and related products - Google Patents

Automatic sampling system, method and related products Download PDF

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Publication number
CN118090321A
CN118090321A CN202410087787.3A CN202410087787A CN118090321A CN 118090321 A CN118090321 A CN 118090321A CN 202410087787 A CN202410087787 A CN 202410087787A CN 118090321 A CN118090321 A CN 118090321A
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China
Prior art keywords
sampling
sampled
fermentation tank
syringe
fermentation
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CN202410087787.3A
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Chinese (zh)
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陈风义
徐安杰
朱洁
谭丰
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Hangzhou Enhe Biotechnology Co ltd
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Hangzhou Enhe Biotechnology Co ltd
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Priority to CN202410087787.3A priority Critical patent/CN118090321A/en
Publication of CN118090321A publication Critical patent/CN118090321A/en
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Abstract

The present disclosure provides an automatic sampling system, method and related products. The automatic sampling system is provided with fermentation tanks, a sampling pipe is arranged in each fermentation tank, and a valve assembly, a peristaltic pump and a syringe are arranged outside each fermentation tank; the injector bracket is used for accommodating the corresponding injector of each fermentation tank; a syringe support moving assembly for moving the syringe support in a plane and up and down; a sampling orifice plate; assembling a robot; a sample area electronic balance; the control equipment is in communication connection with each valve assembly, each peristaltic pump, the syringe support moving assembly, the assembly robot and the electronic balance of the sampling area; a waste liquid container. Through the setting of automatic sampling system and through the cooperation sampling flow, can realize automatic sampling, and include all insoluble substances such as particulate matter in the fermentation broth of getting, and then can be used to various analyses, and the sampling process also can avoid miscellaneous fungus to pollute, but also the mass balance of analysis automatic sampling system and the balanced condition of carbon reduce human labor cost.

Description

Automatic sampling system, method and related products
Technical Field
The present disclosure relates to the field of biological fermentation broth sampling techniques, and in particular to an automatic sampling system, method and related products.
Background
In order to analyze various indexes of the biological fermentation liquid, the fermentation liquid in the fermentation tank needs to be sampled, and the current state of the fermentation liquid in the fermentation tank is judged by analyzing the sampled liquid. The current sampling means mainly comprise two types of manual sampling and automatic sampling.
Manual sampling process needs artifical repeatability operation, leads to artifical intensity of labour big, and the human cost is high. In addition, there is a possibility of errors in manual operations, particularly in the case of large fermentation fluxes (for example >24 fermentation tanks per day), which also easily cause sample confusion.
And the automatic sampling can replace part of manual labor, so that the labor cost is reduced. However, in the current automatic sampling system, in order to prevent the interior of the fermentation tank from being polluted by the foreign bacteria introduced during the sampling process, most of the supernatant liquid (the fermentation liquid is liquid obtained by inoculating strains and culturing the culture medium for a period of time, and the supernatant liquid of the fermentation liquid is clear liquid of the upper layer of the fermentation liquid after centrifugation) in the fermentation liquid is extracted through a ceramic membrane filtration sampler, and cells and insoluble substances are intercepted in the fermentation tank. This sampling method is inconvenient because only the fermentation supernatant is taken:
First, frequent sampling will continuously concentrate the cell concentration of the fermentation broth, enriching the cells. The detection significance of the sample is greatly reduced, and in the period long project, the end point data such as the cell concentration and the yield of the fermentation broth finally obtained by analyzing the sampling liquid have certain deviation, so that the influence of the sampling amount on the fermentation process cannot be accurately estimated.
Secondly, as only the supernatant is taken, the indexes which can be detected for the sampling liquid are limited, the biochemical analysis can be only carried out, and other indexes can not be detected when biochemical indexes such as sugar nitrogen phosphorus and the like in the fermentation liquid are detected. For example, the following items cannot be detected: in biological fermentation, it is very important to measure biomass by turbidimetry OD, cell dry weight method DCW or cell wet weight method WCW, etc., cell viability index such as living cell count, etc., or intracellular material concentration such as organic acid, target product, intermediate metabolite, etc.
Third, existing sampling systems do not take into account mass balance issues. While mass balance (mass balance) and carbon balance (carbon balance) are very important in a bio-fermentation system. Wherein:
Mass balance refers to the accurate metering and tracking of the mass of all material components in one system. The purpose of mass balancing is to ensure that a balance is achieved between the input and output of material in the system to better understand and control the material flow of the system.
The application of mass balance in biological fermentation mainly comprises the following aspects:
a) Substrate utilization: the mass balance helps to track the consumption of substrate during fermentation. By measuring the input of the substrate and the output of the product, the utilization efficiency of the substrate can be calculated. This is important for optimizing the fermentation process and for determining the appropriate substrate supply strategy.
B) The product is formed: mass balance allows measurement of product formation during fermentation. By quantifying the yield of the product, scientists can assess the yield and efficiency of the fermentation process. If the mass balance indicates that the product yield is lower than expected, the fermentation process can be optimized by adjusting the conditions of nutrient supply, pH, temperature or oxygen supply.
C) Biomass growth: the mass balance also helps to monitor the growth of microorganisms during fermentation. By measuring the increase in biomass, scientists can assess the growth rate and overall health of microorganisms. If the mass balance indicates insufficient biomass growth, adjustments can be made by optimizing nutrient supply or other growth conditions.
D) Loss and efficiency: mass balance can identify any loss or inefficiency in the fermentation process and stage. By comparing the input and output qualities of the components, scientists can determine where the loss occurs, such as evaporation, product degradation, or incomplete substrate utilization. Such information may guide process optimization, reducing losses.
Carbon balance refers to the accurate metering and tracking of carbon input and output in one system. It is a special form of mass balance, focusing on tracking and measuring carbon flow during chemical, biological and environmental processes.
The carbon balance is similar to the mass balance, only the carbon element is accurately focused from the whole mass, and the carbon balance has wide application in biological fermentation.
The applicant found that the mass balance can be maintained at 100% and the carbon balance at 95% or more by manual sampling. This can provide a strong precision support for accurate fermentation. Under the precision, the stage with low substrate utilization rate in the fermentation process can be found, and the stage is accurately regulated and controlled, so that the overall fermentation efficiency and yield are finally improved. With most of the automatic sampling devices commercially available, the mass balance was reduced from 100% to less than 95%, and the carbon balance was reduced from 95% to less than 87%.
Disclosure of Invention
The present disclosure presents an automatic sampling system and method.
In a first aspect, the present disclosure provides an automatic sampling system comprising:
The fermentation device comprises at least one fermentation tank, wherein a sampling tube is arranged inside each fermentation tank, a valve assembly, a peristaltic pump and a syringe are arranged outside each fermentation tank, the sampling tube of each fermentation tank is sequentially communicated with the corresponding valve assembly, peristaltic pump and syringe through pipelines, the valve assembly comprises a fermentation liquor valve, an air valve and a cleaning fluid valve, one ends of the fermentation liquor valve, the air valve and the cleaning fluid valve are respectively communicated with the corresponding peristaltic pumps, and the other ends of the fermentation liquor valve, the air valve and the cleaning fluid valve are respectively communicated with the sampling tube, the air source and the cleaning fluid container of the corresponding fermentation tank;
the syringe brackets are used for accommodating syringes corresponding to the fermentation tanks, the top of each syringe is provided with a pressing pad, the bottom of each syringe is provided with a needle, and the needle is vertically arranged in an accommodating hole of each syringe bracket downwards;
A syringe support moving assembly for moving the syringe support in a plane and up and down, the syringe support being fixed to the syringe support moving assembly;
a sampling orifice plate having at least one aperture for receiving a liquid;
The assembly robot is used for moving to the upper part of the syringe bracket and pressing the pressing pad of the syringe so that the syringe moves downwards to the position that the needle is positioned in the hole site of the sampling pore plate;
the electronic balance of the sampling area is arranged in the sampling area and used for weighing the mass in the sampling process;
The control equipment is in communication connection with each valve assembly, each peristaltic pump, the syringe support moving assembly, the assembly robot and the sampling area electronic balance; and
A waste liquid container for containing liquid.
In some alternative embodiments, the assembly robot selects a compliant assembly robot arm.
In some alternative embodiments, a respective fermentation zone electronic balance is provided below each fermenter, the fermentation zone electronic balance being used to weigh the mass of the fermenter above.
In some alternative embodiments, the automatic sampling system further comprises:
The mechanical arm is used for clamping and moving the sampling pore plate; preferably, the mechanical arm is further used for clamping and moving the waste liquid container.
In some alternative embodiments, the automatic sampling system further comprises:
And a needle cleaning liquid container having an opening formed above, through which a needle can be accommodated in the needle cleaning liquid container when each of the syringes is placed in the syringe holder, for cleaning the needle of each of the syringes by the accommodated cleaning liquid.
In some optional embodiments, the sampling area electronic balance is provided with a measured object positioning structure matched with the bottom of the sampling pore plate, the measured object positioning structure is used for detachably fixing the sampling pore plate, the front end of the mechanical arm is provided with a clamping jaw along a first direction, and the automatic sampling system further comprises:
The secondary positioning device is arranged in a secondary positioning area and comprises a first control valve, a second control valve, a position sensor and a secondary positioning limiting assembly, the first control valve and the second control valve are used for moving according to position information detected by the position sensor, so that adjacent first outer side walls and second outer side walls of the sampling pore plate are respectively detachably abutted to the first inner side wall and the second inner side wall of the secondary positioning limiting assembly, an intersection point between horizontal projection of the first inner side wall and horizontal projection of the second inner side wall of the secondary positioning limiting assembly is a reference positioning point, a preset sampling positioning point in horizontal projection of a measured object positioning structure is fixed with a relative position between the reference positioning point, and the mechanical arm can move along the first direction only from the reference positioning point to reach the preset sampling positioning point.
In some alternative embodiments, the syringe comprises:
The needle tube comprises a needle head and a needle tail;
The lower end of the connecting pipe is detachably communicated with the needle tail;
the pipeline connecting piece is hollow, the lower end of the pipeline connecting piece is detachably communicated with the upper end of the connecting pipe, the upper end of the pipeline connecting piece is communicated with an output pipeline of the syringe corresponding to the peristaltic pump, and the outer wall of the pipeline connecting piece is provided with a groove;
The lower end of the needle tube feeding support is in an open arrangement, the connecting tube and the pipeline connecting piece are arranged in the needle tube feeding support, the needle tube feeding support is provided with a clamping structure, the clamping structure is matched with and embedded in a groove arranged on the outer wall of the pipeline connecting piece, a pipeline inlet is formed in the side wall of the needle tube feeding support, and an output pipeline of the injector corresponding to the peristaltic pump can pass through the pipeline inlet from the outside of the needle tube feeding support and enter the inside of the needle tube feeding support;
the push rod is fixedly arranged at the upper end of the needle feeding bracket;
the pressing pad is fixedly arranged at the upper end of the push rod;
The spring is sleeved outside the push rod, the upper end and the lower end of the spring are respectively abutted to the pressing pad and the needle tube feeding support, and the spring is used for enabling the whole injector to move upwards.
In some alternative embodiments, the sampling orifice plate is provided with an identification code, and the automatic sampling system further comprises:
the first identity recognition device is arranged in the first identity recognition area and is in communication connection with the control device;
preferably, the waste liquid container is provided with an identification code, and the automatic sampling system further comprises:
the second identity recognition device is arranged in the second identity recognition area and is in communication connection with the control device.
In a second aspect, the present disclosure provides an automatic sampling method applied to the automatic sampling system described in any implementation manner of the first aspect, the method comprising:
Performing a sampling operation, the sampling operation comprising:
placing the sampling pore plate in a sampling position above the electronic balance of the sampling area;
the injector support is positioned above the sampling pore plate through the movement of the injector support moving assembly, and each injector is respectively and correspondingly positioned above the hole site of the sampling pore plate;
For each fermenter to be sampled, the following fermenter sampling operation is performed: the electronic balance of the sampling area measures the mass to obtain the mass before sampling of the sampling pore plate; the assembling robot presses a pressing pad at the top of the injector corresponding to the fermentation tank to be sampled, so that the corresponding injector moves downwards and the needle tube enters a target hole site corresponding to the fermentation tank to be sampled in the sampling pore plate; opening a fermentation liquor valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the target sampling quality corresponding to the fermentation tank to be sampled, and enabling the pumped fermentation liquor to flow into the corresponding target hole site through a corresponding injector; closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled; opening an air valve of the fermentation tank to be sampled so as to blow a pipeline of the fermentation tank to be sampled, a peristaltic pump and fermentation liquor in an injector into a corresponding target hole site; the electronic balance of the sampling area measures the mass to obtain the sampled mass of the sampling pore plate; determining and recording the fermentation liquor sampling quality of the fermentation tank to be sampled based on the pre-sampling quality and the post-sampling quality of the target sampling pore plate, and completing the fermentation tank sampling operation of the fermentation tank to be sampled;
and taking away the sampling pore plate to finish the sampling.
In some alternative embodiments, the method further comprises performing a waste fluid draining operation prior to performing the sampling operation, the waste fluid draining operation comprising:
placing the waste liquid container at a sampling position on the electronic balance of the sampling area;
Positioning the syringe support above the waste container by movement of the syringe support movement assembly, and each syringe being operable to inject liquid into the waste container;
For each fermenter to be sampled, the following sampling tube waste discharge operation was performed: the electronic balance of the sampling area measures the mass to obtain the pre-liquid-discharge mass of the waste liquid container; opening a fermentation liquor valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor, and enabling the pumped fermentation liquor to flow into the waste liquid container through a corresponding injector; closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled; the electronic balance of the sampling area measures the mass to obtain the discharged liquid mass of the waste liquid container; determining and recording the quality of the waste liquid of the sampling tube of the fermentation tank to be sampled based on the quality before and after the liquid discharge of the waste liquid container, and completing the operation of discharging the waste liquid of the sampling tube of the fermentation tank to be sampled;
Removing the waste liquid container;
preferably, pouring the liquid in the waste liquid container is also included.
In some alternative embodiments, after performing the sampling operation, the method further comprises: executing a pipeline cleaning operation, wherein the pipeline cleaning operation specifically comprises the following steps:
placing the waste liquid container at a sampling position on the electronic balance of the sampling area;
Positioning the syringe support above the waste container by movement of the syringe support movement assembly, and each syringe being operable to inject liquid into the waste container;
For each fermenter to be sampled, the following fermenter line cleaning operation is performed: opening a cleaning liquid valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump cleaning liquid, and cleaning a pipeline, the peristaltic pump and the injector of the fermentation tank to be sampled, wherein the cleaned cleaning liquid flows into the waste liquid container from the injector of the fermentation tank to be sampled; closing a cleaning liquid valve of the fermentation tank to be sampled; opening an air valve of the fermentation tank to be sampled so as to blow residual liquid in a pipeline, a peristaltic pump and an injector of the fermentation tank to be sampled into the waste liquid container, and completing the fermentation tank pipeline cleaning operation of the fermentation tank to be sampled;
Removing the waste liquid container;
Preferably, further comprising pouring the liquid in the waste liquid container;
Preferably, in the fermenter pipe cleaning operation, before opening the cleaning liquid valve of the fermenter to be sampled, the method further includes: the electronic balance of the sampling area measures the mass to obtain the mass of the waste liquid container before the pipeline is cleaned; and after opening an air valve of the fermenter to be sampled to empty the remaining liquid in the pipe of the fermenter to be sampled, further comprising: and measuring the mass by the electronic balance in the sampling area to obtain the mass of the waste liquid container after the pipeline is cleaned.
In some alternative embodiments, the method further comprises performing a needle cleaning operation prior to performing the waste fluid draining operation or prior to performing the sampling operation, the needle cleaning operation comprising:
Causing each of the syringe needles accommodated by the syringe holder to be accommodated in the needle cleaning liquid container through a top opening of the needle cleaning liquid container by movement of the syringe holder moving assembly so as to be cleaned by the accommodated cleaning liquid;
Each of the syringe needles received by the syringe support is moved away from the needle wash container by movement of the syringe support movement assembly.
Removing the needle cleaning liquid container;
preferably, further comprising pouring the liquid in the needle cleaning liquid container;
Preferably, in the needle cleaning operation, before each of the syringe needles accommodated in the syringe holder is accommodated in the needle cleaning solution container through the top opening of the needle cleaning solution container by the movement of the syringe holder moving assembly, further comprising: and placing the needle head cleaning liquid container at a sampling position on the electronic balance in the sampling area.
In some alternative embodiments, after performing the line cleaning operation, the method further comprises: the needle cleaning operation is performed again.
In some alternative embodiments, the step of starting the peristaltic pump of the fermentation tank to be sampled pumps the fermentation liquid according to the target sampling quality corresponding to the fermentation tank to be sampled includes:
Determining first target sampling quality according to the target sampling quality corresponding to the fermentation tank to be sampled, wherein the first target sampling quality is smaller than the target sampling quality;
determining the first working time length of a peristaltic pump of the fermentation tank to be sampled according to the first target sampling quality and a preset pump speed;
Starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the preset pump speed and the first working time;
closing a peristaltic pump of the fermentation tank to be sampled;
the electronic balance of the sampling area measures the mass to obtain the first sampled mass of the sampling pore plate;
Determining a first actual sampling quality based on a pre-sampling quality and a first post-sampling quality of the sampling orifice plate;
determining an actual pump speed according to the first actual sampling quality, the first target sampling quality and the preset pump speed;
In response to determining that the actual pump speed is less than a preset minimum pump speed, interrupting the fermenter sampling operation, generating and outputting prompt information for indicating that there is a risk of pipeline blockage or air leakage;
In response to determining that the actual pump speed is not less than a preset minimum pump speed and is less than a preset maximum pump speed, determining a secondary sampling working time length based on the actual pump speed and a residual to-be-sampled mass obtained by subtracting the first actual sampling mass from the target sampling mass, and starting a peristaltic pump of the to-be-sampled fermentation tank to pump fermentation liquor according to the preset pump speed and the secondary sampling working time length;
And in response to determining that the actual pump speed is greater than a preset highest pump speed, modifying the pump speed of the peristaltic pump of the fermentation tank to be sampled, determining a secondary sampling working time length based on the modified pump speed and the residual sampling quality obtained by subtracting the first actual sampling quality from the target sampling quality, and starting the peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the modified pump speed and the secondary working sampling time length.
In some alternative embodiments, the method further comprises:
Before the first sampling, connecting each pipeline connected with each valve component to the cleaning liquid container, opening each valve component and each peristaltic pump to enable the cleaning liquid to sequentially flow through each valve component, the peristaltic pump, the injector and the corresponding pipeline, and injecting the cleaning liquid into the waste liquid container for the first pipeline cleaning;
And restoring the pipeline connecting structure of each valve assembly.
In some alternative embodiments, the sampling orifice plate is provided with an identification code, and the automatic sampling system further comprises a first identification device disposed in the first identification zone and communicatively coupled to the control device; and
The sample position of placing the sampling pore plate on the electronic balance of the sampling area comprises:
Placing the sampling pore plate in a first identification area corresponding to first identification equipment for identification;
And responding to the verification passing of the sampling pore plate according to the identification result of the identity information of the sampling pore plate, and placing the sampling pore plate in a sampling position on the electronic balance of the sampling area.
In some alternative embodiments, the waste container is provided with an identification code, and the automatic sampling system further comprises a second identification device disposed in a second identification zone and communicatively connected to the control device; and
The placing of the waste liquid container in the sampling position on the sampling area electronic balance comprises:
placing the waste liquid container in a second identity recognition area corresponding to second identity recognition equipment for identity recognition;
And responding to the verification passing of the waste liquid container according to the identification result of the identity information of the waste liquid container, and placing the waste liquid container at a sampling position on the electronic balance of the sampling area.
In some optional embodiments, the automatic sampling system further includes a secondary positioning device disposed in the secondary positioning area, the secondary positioning device including a first control valve, a second control valve, a position sensor, and a secondary positioning limiting component, at least two adjacent outer side walls of the sampling orifice plate being matable to a structural inner wall of the secondary positioning limiting component, the first control valve and the second control valve being configured to move according to position information detected by the position sensor, so as to detachably abut at least two adjacent outer side walls of the sampling orifice plate against the structural inner wall of the secondary positioning limiting component; and
The placing the sampling pore plate at the sampling position on the sampling area electronic balance comprises the following steps:
Placing the sampling pore plate in a secondary positioning area, and performing secondary positioning on the sampling pore plate through the secondary positioning device;
And moving the sampling pore plate from the secondary positioning area to a sampling position on the electronic balance of the sampling area.
In a third aspect, the present disclosure provides a control apparatus comprising: one or more processors; a storage device having one or more programs stored thereon that, when executed by the one or more processors, cause the automatic sampling system described in any of the implementations of the first aspect to implement the method described in any of the implementations of the second aspect.
In a fourth aspect, the present disclosure provides a computer-readable storage medium having stored thereon a computer program, wherein the computer program, when executed by one or more processors, causes the automatic sampling system described in any one of the implementations of the first aspect to implement the method described in any one of the implementations of the second aspect.
In a fifth aspect, the present disclosure provides a computer program product comprising computer programs/instructions which, when executed by a processor, cause an automatic sampling system described in any one of the implementations of the first aspect to implement a method described in any one of the implementations of the second aspect.
According to the automatic sampling system and the automatic sampling method, the fermentation tanks are arranged in the automatic sampling system and used for fermenting biological fermentation liquid, sampling pipes are arranged in each fermentation tank, a valve assembly, a peristaltic pump and a syringe are arranged outside each fermentation tank, the sampling pipes of each fermentation tank are sequentially communicated with the corresponding valve assembly, peristaltic pump and syringe through pipelines, each valve assembly comprises a fermentation liquid valve, an air valve and a cleaning liquid valve, one end of each fermentation liquid valve, one end of each air valve and one end of each cleaning liquid valve are respectively communicated with the corresponding peristaltic pump, and the other end of each fermentation liquid valve, the corresponding peristaltic pump, the corresponding sampling pipe of each fermentation tank, the corresponding air source and the corresponding cleaning liquid container are respectively communicated with each other; the syringe brackets are used for accommodating syringes corresponding to the fermentation tanks, the top of each syringe is provided with a pressing pad, the bottom of each syringe is provided with a needle, and the needle is vertically arranged in the accommodating hole of each syringe bracket downwards; the syringe support moving assembly is used for moving the syringe support in a plane and up and down, and the syringe support is fixed on the syringe support moving assembly; a sampling orifice plate having at least one aperture for receiving a liquid; the assembly robot is used for moving to the upper part of the syringe bracket and pressing the pressing pad of the syringe so that the syringe moves downwards to the position that the needle is positioned in the hole site of the sampling pore plate; the electronic balance of the sampling area is arranged in the sampling area and used for weighing the mass in the sampling process; the control equipment is in communication connection with each valve assembly, each peristaltic pump, the syringe support moving assembly, the assembly robot and the electronic balance of the sampling area; and a waste liquid container for containing a liquid. That is, by setting the above-mentioned automatic sampling system and by cooperating with the sampling flow, the following technical effects can be achieved, including but not limited to:
first, keep apart each fermentation cylinder each other, and each is independently provided with valve assembly, peristaltic pump and syringe, can avoid mixing up between the fermentation broth of different types.
Second, by providing a sampling tube in the fermenter instead of using a sampler with a filtering function, all water-insoluble substances such as particulate matters can be obtained through the sampling tube, and the fermentation broth sampled through the sampling tube can be used for various other analyses, compared with the case where only the supernatant can be obtained by the sampler with a filtering function. The quality of the fermentation liquor sampled by adopting the sampling tube is basically the same as that of the fermentation liquor sampled by hand, and the fermentation liquor can completely cover all purposes.
Thirdly, the reason for adopting the sampler with the filtering function in the prior art is that: the fermentation liquor in the fermentation tank is prevented from being polluted by external microorganisms in the automatic sampling process. In the present disclosure, although a sampler with a filtering function is not adopted, a sampling tube is adopted, but a fermentation liquid valve, an air valve and a cleaning liquid valve are provided for each fermentation tank, the cleaning liquid valve is communicated with a cleaning liquid container, and cleaning liquid is adopted to clean and disinfect a pipeline, a peristaltic pump and a syringe, so that the syringe and a needle are prevented from being contaminated by bacteria. The air valve and the clean air source can be used for drying the pipeline, the peristaltic pump and the injector, so that the contamination of bacteria is avoided, and the residue of cleaning liquid and waste liquid in the pipeline can be avoided. And further, the automatic sampling by adopting the sampling tube can also avoid the contamination of mixed bacteria.
Fourth, through setting up the sample district electronic balance, can weigh the sample orifice plate quality of each stage of sample in real time, and then through the quality of real-time detection, the mass balance and the carbon balance condition of analysis automatic sampling system.
Fifthly, automatic sampling is achieved through the integral arrangement of the automatic sampling system, and labor cost is reduced.
Drawings
Other features, objects and advantages of the present disclosure will become more apparent upon reading of the detailed description of non-limiting embodiments, made with reference to the following drawings:
FIG. 1 is an exemplary structural schematic diagram of one embodiment of an automatic sampling system according to the present disclosure;
FIG. 2 is an exemplary schematic diagram of a circuit according to one embodiment of an automatic sampling system of the present disclosure;
FIG. 3 is an exemplary structural schematic diagram of one embodiment of a secondary positioning device according to the present disclosure;
FIG. 4A is an exemplary structural schematic diagram of one embodiment of a syringe support movement assembly according to the present disclosure;
FIG. 4B is an exemplary structural schematic diagram of a first view of one embodiment of a syringe according to the present disclosure;
FIG. 4C is an exploded view of the syringe of FIG. 4B at a first angle;
FIG. 4D is an exploded view of the syringe of FIG. 4B at a second angle;
FIG. 5A is a flow chart of one embodiment of an auto-sampling method according to the present disclosure;
FIG. 5B is an exploded flow chart according to one embodiment of step 501 of the present disclosure;
FIG. 5C is an exploded flow chart of one embodiment of step 5013 in accordance with the present disclosure;
FIG. 5D is an exploded flow chart of one embodiment of step 50134 according to the present disclosure;
FIG. 5E is an exploded flow chart according to one embodiment of step 502 of the present disclosure;
FIG. 5F is an exploded flow chart according to one embodiment of step 5023 of the present disclosure;
FIG. 5G is an exploded flow chart of one embodiment of step 503 according to the present disclosure;
FIG. 5H is an exploded flow chart according to one embodiment of step 5033 of the present disclosure;
fig. 5I is an exploded flow chart of one embodiment of step 504 according to the present disclosure.
Detailed Description
The present disclosure is described in further detail below with reference to the drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting of the invention. It should be noted that, for convenience of description, only the portions related to the present invention are shown in the drawings.
It should be noted that, without conflict, the embodiments of the present disclosure and features of the embodiments may be combined with each other. The present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
Referring to fig. 1 and 2, fig. 1 shows a schematic diagram of the structure of one embodiment of an automatic sampling system according to the present disclosure, and fig. 2 shows a schematic diagram of the communication lines between a fermenter, a valve assembly, a peristaltic pump, and a syringe according to the present disclosure.
As shown in fig. 1 and 2, the automatic sampling system 10 may include: fermentors 110, 120, 130, 140, 150, 160, 170, 180, syringe support 190, syringe support movement assembly 200, sampling orifice 210, assembly robot 220, sampling area electronic balance 230, control device 240, and waste container 250.
As shown in fig. 2, sampling pipes 111, 121, 131, 141, 151, 161, 171, 181 are provided inside the fermentation tanks 110, 120, 130, 140, 150, 160, 170, 180, respectively. The sampling tube can be communicated with the inside and the outside of the fermentation tank, and the fermentation liquid in the fermentation tank can be sampled through the sampling tube.
Optionally, the interior of the fermentors 110, 120, 130, 140, 150, 160, 170, 180 may also be provided with stirring paddles for stirring the fermentation broth inside the fermentors so that the fermentation broth concentration inside the fermentors remains uniform. Thus, the fermentation liquid sampled by the sampling tube is taken out in a completely liquid state in a uniformly mixed state.
As shown in fig. 2, the valve assemblies 112, 122, 132, 142, 152, 162, 172, 182, peristaltic pumps 113, 123, 133, 143, 153, 163, 173, 183, and syringes 114, 124, 134, 144, 154, 164, 174, 184 are disposed outside the fermentors 110, 120, 130, 140, 150, 160, 170, 180, respectively.
The sampling tube of each fermentation tank is sequentially communicated with the corresponding valve component, peristaltic pump and injector through pipelines. Here, the term "communicating" means that a liquid can flow therethrough.
For example, the sampling tube 111 of the fermenter 110 is connected in series with a corresponding valve assembly 112, peristaltic pump 113 and syringe 114 via tubing. The sampling tube 112 of the fermenter 120 is connected in series with a corresponding valve assembly 122, peristaltic pump 123 and syringe 124 via tubing. The other fermentors 130, 140, 150, 160, 170, 180 are in substantially the same communication with the corresponding valve assemblies, peristaltic pumps, and syringes, and will not be described in detail herein.
Wherein each valve assembly may include a broth valve, an air valve, and a rinse valve. For example, valve assembly 112 includes a broth valve 1121, an air valve 1122, and a rinse valve 1123, valve assembly 122 includes a broth valve 1221, an air valve 1222, and a rinse valve 1223, and the other valve assemblies 132, 142, 152, 162, 172, and 182 also include corresponding broth, air, and rinse valves, which are not described in detail herein. One end of each fermentation liquor valve, one end of each air valve and one end of each cleaning liquid valve are respectively communicated with corresponding peristaltic pumps, and the other ends of the fermentation liquor valves are respectively communicated with sampling tubes, air sources and cleaning liquid containers of corresponding fermentation tanks. For example, the broth valve 1121 communicates at one end with peristaltic pump 113 and at the other end with the sampling tube 111 of the fermentor 110, the air valve 1122 communicates at one end with peristaltic pump 113 and at the other end with a clean air source (not shown in FIG. 2), and the cleaning fluid valve 1123 communicates at one end with peristaltic pump 113 and at the other end with a cleaning fluid container (not shown in FIG. 2). The cleaning solution container contains a cleaning solution, which may be various liquids having sterilizing and disinfecting functions, such as alcohol, hydrogen peroxide, etc., which is not particularly limited in the present disclosure. The cleaning liquid container may be, for example, a glass container, a stainless steel container, a polypropylene container, or the like.
The syringe holders 190 are used to accommodate corresponding syringes for each fermenter. As shown in fig. 1, the syringe support 190 is used to house the syringes 114, 124, 134, 144, 154, 164, 174, 184. The syringe support 190 may be provided with corresponding receiving holes, and each syringe may be received in a different receiving hole. The receiving holes of the syringe holder 190 are isolated from each other. Alternatively, the receiving holes of the syringe support 190 may be regularly arranged, for example, in an array in two perpendicular directions, or alternatively, may be staggered in an array in two perpendicular directions.
The top of each syringe may be provided with a push pad and the bottom with a needle. Each syringe may be placed vertically needle-down into the receiving bore of the syringe support 190.
The syringe support movement assembly 200 is used to move the syringe support 190 in a planar and up and down direction. The syringe support 190 is secured to the syringe support movement assembly 200. Specifically, referring to fig. 4A, fig. 4A is a schematic diagram of one embodiment of a syringe support movement assembly 200 according to the present disclosure. As shown in fig. 4A, the syringe support moving assembly 200 may include a first stepping motor 201, a first slider 202 fixedly coupled to the first stepping motor 201, and a first rail 203 coupled to the first slider 202, a second stepping motor 204, a second slider 205 fixedly coupled to the second stepping motor 204, and a second rail 206 coupled to the second slider 205.
Wherein:
The first stepper motor 201 may drive the first slider 202 to move along the first track 203 under the control of the pulse signal. The second stepping motor 204 can drive the second slider 205 to move along the second track 206 under the control of the pulse signal.
The extending direction of the first rail 203 is parallel to the horizontal plane, and the extending direction of the second rail 206 may be perpendicular to the horizontal plane.
The syringe support 190 may be fixed to the second slider 205, so that under the control of the pulse signal, the second stepper motor 204 may drive the second slider 205 and the syringe support 190 to move along the extending direction of the second track 206, i.e. the direction perpendicular to the horizontal plane, that is, may realize the up-and-down movement of the syringe support 190.
The bottom of the second track 206 is fixed to the first slider 202, so that under the control of the pulse signal, the first stepper motor 201 can drive the first slider 202, the second track 206, the second slider 205 and the syringe support 190 to move along the extending direction of the first track 203, i.e. in the horizontal plane (e.g. in the front-back direction), i.e. can realize the movement of the horizontal plane of the syringe support 190 (e.g. in the front-back direction).
The up-down and back-and-forth movement of the syringe support 190 may be accomplished by a combination of the various stepper motors, sliders and rails described above.
The sampling orifice 210 has at least one well for containing a fluid, the wells being isolated from one another. Alternatively, the sites of sampling orifice plate 210 may be regularly spaced, for example, in an array in two perpendicular directions, or may be circular or arcuate about a central point.
In order to ensure that the fermentation broth taken by the sampling orifice 210 is not contaminated by foreign bacteria, a sealed hole cover, such as a silica gel cover, may be disposed above the hole of the sampling orifice 210.
It should be noted that the sampling orifice 210 may be disposed at a sampling position above the electronic balance 230 in the sampling area during sampling, and may be disposed in other areas before or after sampling, for example, in a refrigerator or in an orifice bin. When required, is moved to a sampling position above the sample area electronic balance 230 by a manual or robotic arm.
The assembly robot 220 is used to move over the syringe support 190 and press the syringe's press pad so that the syringe moves down to the site cover of the needle-stick sampling orifice plate 210 and into the site. The assembly robot 220 may be a variety of robots having a function of moving in a horizontal plane direction and performing assembly in a vertical direction.
In some alternative embodiments, the assembly robot 220 may be a selective compliance assembly robot arm (SCARA, SELECTIVE COMPLIANCE ASSEMBLY ROBOT ARM) for planar positioning and vertical direction assembly.
The sample area electronic balance 230 is used to weigh the mass during sampling. The area of the sample area electronic balance 230 may be referred to as the sample area. The sample area electronic balance 230 may send the weighed mass data to the control device 240. Above the sample area electronic balance 230 may be provided a sample position, which is the position where the sampling orifice plate 210 is located when sampling.
The control device 240 is communicatively coupled to each valve assembly, each peristaltic pump, syringe support movement assembly 200, assembly robot 220, and sample area electronic balance 230. The control device 240 is configured to execute an auto-sampling command stored locally or received remotely from an upper computer (not shown in fig. 1 and 2) connected to the control device 240 via a remote network, and send the auto-sampling command to each valve assembly, each peristaltic pump, the syringe support moving assembly 200, the assembly robot 220, and the sample area electronic balance 230, which need to perform corresponding operations, respectively, after the auto-sampling command is decomposed. For example, control device 240 may send instructions to a specific designated broth, air, or wash fluid valve to control the opening or closing of the corresponding broth, air, or wash fluid valve. The command can also be sent to a specific appointed peristaltic pump, and the corresponding peristaltic pump is controlled to be opened and operated according to what pump speed and for how long, or stopped. Instructions may also be sent to the syringe support movement assembly 200 to control the displacement of the syringe support movement assembly 200 in a horizontal direction, as well as the displacement of the syringe support movement assembly in a vertical direction. It is also possible to send instructions to the assembly robot 220, control the displacement of the assembly robot 220 to move in the horizontal direction, and the assembly work in the vertical direction. Instructions may also be sent to the sample area electronic balance 230 to control the sample area electronic balance 230 to weigh and obtain the weighed mass from the sample area electronic balance 230.
The control device 240 may be various electronic devices having logic operations, data storage, and data communication functions. For example, the control device 240 may be a separately provided controller, such as a programmable logic controller (PLC, programmable Logic Controller), a single-chip microcomputer, an industrial controller, a desktop computer, a notebook computer, a server, or the like; or equipment composed of other electronic devices with input/output ports and operation control functions. For example, the control device 240 may include, but is not limited to, the following: FPGA (Field Programmable GATE ARRAY ), ASIC (Application SPECIFIC INTEGRATED Circuit), central Processing Unit (CPU), etc.
The waste container 250 is used to hold the sample waste during sampling, i.e. the sample waste is also the fermentation broth from the fermenter, but is not taken into the sampling orifice, such as fermentation broth remaining in the sampling tube, tubing, peristaltic pump or syringe. The remaining fermentation liquid may be considered as a sampling waste liquid, and the sampling waste liquid is not derived from the real-time fermentation liquid in the fermentation tank, and cannot represent the real-time condition of the fermentation tank, and therefore, the residual fermentation liquid needs to be discharged, and the container for containing the sampling waste liquid is referred to as a waste liquid container. However, in order to achieve mass balance and carbon balance, it is necessary to record the mass of the sampled waste liquid, and therefore, it is also necessary for the sample area electronic balance 230 to weigh the mass of the waste liquid container 250 before and after the waste liquid discharge, determine the mass of the sampled waste liquid according to the mass difference, and record the mass of the sampled waste liquid.
The waste container 250 may be a container having an inner accommodating space.
Alternatively, the waste container 250 may have a plurality of inner accommodating spaces, and the different accommodating spaces may be isolated from each other. For example, waste container 250 may be a similar sampling well plate with a plurality of regularly arranged receiving wells. Alternatively, a sealing cover, which may be a silicone cover, for example, may be provided above each accommodation space of the waste liquid container 250. Alternatively, waste container 250 may be configured identically to sampling orifice 210. Alternatively, the number of holding spaces of the waste liquid container 250 is equal to or greater than the number of fermentation tanks in the automatic sampling system 10, so that separate weighing and holding of waste liquid discharged from different fermentation tanks can be achieved.
Alternatively, the sampling tube may be an internal hollow tube without a filtering function, for example, a stainless steel tube. Thus, the fermentation broth (hereinafter referred to as sampling broth) sampled from the fermentation tank may be unfiltered, and all the substances in the fermentation broth are retained, i.e., the sampling broth is substantially identical to the fermentation broth in the fermentation tank, and the analysis result of the analysis of the sampling broth can accurately evaluate the fermentation process of the fermentation broth in the fermentation tank corresponding to the sampling broth. In addition, since all the substances are obtained, other indexes than biochemical analysis can be detected for the sample liquid, for example, the measurement of biomass by a turbidimetry OD, a cell dry weight method DCW, or a cell wet weight WCW, which are very important in biological fermentation, cell viability indexes such as living cell count, or intracellular substance concentrations such as organic acids, target products, intermediate metabolites, and the like can be detected. In some alternative embodiments, each fermenter may be provided with a respective fermentation area electronic balance (not shown in fig. 1 and 2) for weighing the mass of the fermenter above. The control device 240 may be communicatively connected to each of the electronic balances for controlling the electronic balances to weigh and obtain the fermenter mass weighed by the electronic balances.
In some alternative embodiments, the automatic sampling system 10 may also include a robotic arm 260. The robotic arm 260 is used to grip and move the sampling orifice plate 210. Alternatively, the robotic arm 260 may also be used to grip and move the waste container 250. It should be noted that the control device 240 may control the mechanical arm 260, and thus, the mechanical arm 260 is in communication with the control device 240. The mechanical arm 260 may also be controlled by an upper computer connected to the control device 240 through a network, which is not specifically limited in the disclosure, and correspondingly, the mechanical arm 260 is connected to the upper computer through communication.
In some alternative embodiments, the automatic sampling system 10 can further include a needle wash container 270. The upper side of the needle cleaning liquid container 270 has an opening, and when each syringe is placed in the syringe holder 190, if the needle cleaning liquid container 270 is placed in a proper position under the syringe holder 190, the needle of each syringe can be accommodated in the needle cleaning liquid container 270 through the opening provided above the needle cleaning liquid container 270, so that the needle of each syringe can be cleaned, sterilized, and disinfected by the cleaning liquid accommodated in the needle cleaning liquid container 270.
In some alternative embodiments, the sample area electronic balance 230 may be provided with a sample positioning structure 2301 that matches the bottom of the sampling orifice plate 210, i.e., the position where the sampling orifice plate 210 is located when sampling, i.e., the sampling position. Here, the object positioning structure 2301 is used to detachably fix the sampling orifice plate 210. For example, when the top of object positioning structure 2301 may be provided with a recess, the bottom of sampling orifice plate 210 may detachably mate with the recess of the top of object positioning structure 2301. And, in order to grasp the sampling orifice 210 using the robot arm 260, a front end of the robot arm 260 may be provided with a jaw in the first direction. Here, the first direction can be understood as: when the robot arm 260 is parallel to the horizontal plane, a direction perpendicular to the extending direction (i.e., the front-rear direction) of the robot arm 260 (i.e., the left-right direction). And the automatic sampling system 10 may further include: and the secondary positioning device 280 is arranged in the secondary positioning area. Referring to fig. 3, fig. 3 illustrates a schematic structural diagram of one embodiment of a secondary positioning device 280 in accordance with the disclosure. As shown in fig. 3, the secondary positioning device 280 may include a first control valve 281, a second control valve 282, a position sensor 283 and a secondary positioning limiting assembly 284, where the first control valve 281 and the second control valve 282 are configured to move according to position information detected by the position sensor 283, so that adjacent first outer sidewall 210a and second outer sidewall 210b of the sampling orifice 210 are detachably abutted to a first inner sidewall 284a and a second inner sidewall 284b of the secondary positioning limiting assembly 284, respectively, and an intersection point between a horizontal projection of the first inner sidewall 284a and a horizontal projection of the second inner sidewall 284b of the secondary positioning limiting assembly 284 is a reference positioning point P1, a preset sampling positioning point P2 (please refer to fig. 1) in a horizontal projection of the measured object positioning structure 2301 is fixed in a relative position with the reference positioning point, and the mechanical arm 260 can move from the reference positioning point P1 only along a first direction to reach the preset sampling positioning point P2. This is to take into account that since the mechanical arm 260 is provided with the clamping jaw in the first direction, the mechanical arm 260 is precisely positioned in the first direction, and in other directions, the mechanical arm 260 may have a positioning deviation after several pauses, so before the mechanical arm 260 places the sampling hole plate 210, the waste liquid container 250 or the needle cleaning liquid container 270 at the sampling position on the electronic balance 230 in the sampling area, the mechanical arm 260 may be placed in the secondary positioning area, the secondary positioning is performed by the secondary positioning device 280 to the reference positioning point P1, and then the mechanical arm 260 may move from the reference positioning point P1 to the sampling positioning point P2 only by moving along the first direction, so that no positioning deviation corresponding to other directions is generated, and the positioning accuracy of the mechanical arm 260 for taking and placing the articles on the electronic balance 230 in the sampling area is improved.
Here, the first control valve 281 and the second control valve 282 may be various control valves, and may be, for example, an electric valve, a pneumatic valve, or the like.
In some alternative implementations, please refer to fig. 4B, 4C, and 4D, fig. 4B illustrates a schematic structural view of a first view of an embodiment 114 of a syringe according to the present disclosure, fig. 4C is an exploded view of the syringe at a first angle illustrated in fig. 4B, and fig. 4D is an exploded view of the syringe at a second angle illustrated in fig. 4B. As shown in fig. 4B, 4C, and 4D, the syringe 114 may include: needle cannula 1141, connection tube 1142, tubing connection 1143, needle cannula feed holder 1144, push rod 1145, compression pad 1146, spring 1147, and spring boot 1149. Wherein:
needle cannula 1141 includes a needle 1141A and a needle tail 1141B.
The lower end of the connecting tube 1142 is detachably connected to the needle tail 1141B.
The pipe connector 1143 is hollow, the lower end of the pipe connector 1143 is detachably connected with the upper end of the connecting pipe 1142, the upper end of the pipe connector is connected with the output pipe of the peristaltic pump corresponding to the syringe 114, and the outer wall of the pipe connector is provided with a groove 1143A.
The needle tube feeding bracket 1144 is provided with an open lower end, and a connecting tube 1142 and a pipe connection member 1143 are provided in the needle tube feeding bracket 1144. The needle feeding housing 1144 is further provided with a gripping structure 11441, the gripping structure 11441 being adapted to fit within a recess 1143A provided in the outer wall of the tubing connector 1143. The side wall of the needle feeding bracket 1144 is provided with a tubing inlet 11442, and the output tubing of the syringe 114 corresponding to the peristaltic pump can pass through the tubing inlet 11442 from outside the needle feeding bracket 1144 into the interior of the needle feeding bracket 1144.
The push rod 1145 is fixedly disposed on the upper end of the needle feeding housing 1144.
The pressing pad 1146 is fixedly disposed on the upper end of the push rod 1145.
The spring 1147 is sleeved outside the push rod 1145, and the upper and lower ends of the spring 1147 are respectively abutted with the pressing pad 1146 and the needle tube feeding bracket 1144. Spring 1147 serves to move the syringe 114 generally upward. The spring 1147 is also externally sleeved with a spring boot 1149.
When a sample is to be taken from the fermentor 110, the broth valve 1121 is opened and the peristaltic pump 113 is activated to pump broth from the fermentor 110, and the pumped broth may flow from the output of the peristaltic pump 113 through tubing into tubing connector 1143 in the syringe 114, then into tubing 1142 and tubing 1141 in sequence, and out of the needle 1141A. In order to allow the fermentation broth flowing out of needle 1141A to enter sampling orifice 210 accurately, a sealed orifice cover, such as a silica gel cover, is disposed above the orifice of sampling orifice 210, so that the liquid cannot enter the orifice. Thus, prior to injecting the fermentation broth into the well of sampling orifice 210, the well lid needs to be pierced, that is, needle 1141A of syringe 114 needs to be used to pierce the well lid. To achieve this, the assembly robot 220 is required to press the pressing pad 1146 provided at the top end of the syringe 114, and thus the upper end of the spring 1147 sleeved outside the push rod 1145 is pressed downward by the downward force of the pressing pad 1146, while the bottom end of the spring 1147 is limited by the top end of the syringe bracket 190 and cannot pass through the top end of the syringe bracket 190, and the lower end of the spring 1147 is fixed, so that the spring 1147 is compressed as a whole. The syringe 114 as a whole is also moved downward by the pressing force, so that the needle 1141A is also moved downward to puncture the hole cover, and the liquid can flow from the needle 1141 into the hole of the punctured hole cover of the sampling orifice 210. However, after the hole cover is punctured and the injection of the liquid is completed, the assembling robot 220 may not apply downward force, so as to ensure that the syringe 114 can return to the original position smoothly, at this time, the pressure of the spring 1147 sleeved outside the push rod 1145 is released, so that upward force is formed, and the syringe 114 moves upward entirely under the driving of the above force, so as to return to the original position.
In some alternative embodiments, the lower portion of the needle feeding housing 1144 may further be provided with a limiting structure 1148, wherein the outer diameter of the limiting structure 1148 is larger than the aperture of the receiving hole in the syringe housing 190, so that during the upward movement of the syringe 114, when the limiting structure 1148 reaches the receiving hole of the syringe housing 190, the limiting structure 1148 prevents the syringe 114 from further moving upward, and prevents the syringe 114 from moving excessively upward.
In some alternative embodiments, sampling orifice plate 210 may be provided with an identification code. For example, an identification code may be affixed to the sidewall of sampling orifice plate 210. The identification code may be, for example, a bar code or a two-dimensional code. Accordingly, the automatic sampling system 10 may also include a first identity recognition device 290. The area set by the first identification device 290 is a first identification area. The first identity recognition device 290 is communicatively coupled to the control device 240. The control device 240 may send an instruction to the first identity recognition device 290, so that the first identity recognition device 290 performs an identity information collection operation (for example, code scanning or photographing, etc.), and feeds back the collected identity information (for example, code scanning result or photograph, etc.) to the control device 240. By way of example, the first identity recognition device 290 may be a code scanner, camera, or the like. Then, the control device 240 may perform identification according to the identity information fed back by the first identity recognition device 290 to obtain an identity information recognition result of the sampling orifice plate.
In some alternative embodiments, waste container 250 may also be provided with an identification code, and accordingly, automatic sampling system 10 may also include a second identification appliance 300. The area set by the second identification device 300 is a second identification area. The second identification device 300 is communicatively connected to the control device 240. The control device 240 may send an instruction to the second identification device 300, so that the second identification device 300 performs an identity information collection operation (for example, code scanning or photographing, etc.), and feeds back the collected identity information (for example, code scanning result or photograph, etc.) to the control device 240. As an example, the second identification device 300 may be a code scanner, camera, or the like. Then, the control device 240 may perform recognition according to the identity information fed back by the second identity recognition device 300 to obtain the identity information recognition result of the waste liquid container.
Reference is made to fig. 5A. Fig. 5A illustrates a flow 600 of an auto-sampling method according to the present disclosure, which may be applied to an auto-sampling system as illustrated in fig. 1.
As shown in fig. 5A, the flow 500 of the automatic sampling method includes step 501:
step 501, a sampling operation is performed.
It should be noted that, each step of the flow 500 corresponds to executing an auto-sampling instruction locally stored by the control device 240 or remotely received from an upper computer (not shown in fig. 1 and 2) connected to the control device 240 via a remote network, decomposing the auto-sampling instruction to obtain corresponding instructions executed by different devices in the auto-sampling system, and sending the decomposed instructions to each valve assembly, each peristaltic pump, the syringe support moving assembly 200, the assembly robot 220, the sampling area electronic balance 230 in the auto-sampling system, etc. that need to execute the corresponding instructions. That is, the valve assemblies, peristaltic pumps, syringe support movement assembly 200, assembly robot 220, and sample area electronic balance 230 involved in the steps of flow 500 are all under the control of control device 240, performing the corresponding operations in the order of execution in flow 500.
In this embodiment, since there are a plurality of holes in the sampling orifice, in order to increase the sampling efficiency, samples can be taken from at least one fermenter at a time and injected into different holes in the sampling orifice. Accordingly, the auto-sampling instructions may be used to indicate which fermenters of the auto-sampling system the current sample needs to be sampled from, the sampled fermenters being the fermenters to be sampled, and also to indicate the quality of the fermentation broth sampled from each of the fermenters to be sampled, and also to indicate which specific hole sites in the sampling orifice the fermentation broth sampled from each of the fermenters to be sampled needs to be injected into, and thus, the auto-sampling instructions may include N sampling instructions, each sampling instruction comprising: a fermentation tank mark to be sampled, a target sampling quality and a target hole site mark. N is a natural number. The target hole site mark is used for indicating a specific hole site into which the fermentation broth needs to be transferred, namely the target hole site.
In this embodiment, the sampling operation may specifically include steps 5011 to 5014 as shown in fig. 5B:
step 5011, placing the sampling orifice plate in a sampling position above the sampling area electronic balance.
In this embodiment, sampling orifice 210 may be placed by hand. Alternatively, where the automated sampling system 10 includes a robotic arm 260, the sampling orifice 210 may be positioned by the robotic arm 260. It should be noted that the sampling orifice 210 may be taken from a refrigerator (not shown in fig. 1) or an orifice bin (not shown in fig. 1) and placed in a sampling position above the sample area electronic balance.
Alternatively, the sample site may be, for example, the object positioning structure 2301 above the sample area electronic balance 230.
In order to prevent removal of a non-sampling orifice 210 (e.g., a waste container 250 or a needle wash container 270, etc.) during removal of sampling orifice 210, in some alternative embodiments, sampling orifice 210 may be provided with an identification code, and automatic sampling system 10 may further include a first identification device 290 disposed in the first identification zone and in communication with control device 240. Accordingly, in step 5011, placing sampling orifice plate 210 in a sampling position on sampling area electronic balance 230 may be performed as follows:
First, the sampling orifice 210 is placed in a first identification area corresponding to the first identification device 290 for identification.
For example, the first identity recognition device 290 may be a code scanner or a camera. Accordingly, the identification of the sampling hole plate 210 may take the code scanning result of the code scanning gun as the identification result, or the identification result may be obtained by performing image recognition on the image shot by the camera.
Instructions may be sent by the control device 240 to the first identity recognition device 290 to cause the first identity recognition device 290 to perform an identity information collection operation (e.g., scanning a code or photographing, etc.), and to feed back collected identity information (e.g., scanning a code result or a photograph, etc.) to the control device 240. Then, the control device 240 may perform identification according to the identity information fed back by the first identity recognition device 290 to obtain an identity information recognition result of the sampling orifice plate.
The sampling orifice plate 210 may then be verified based on the identification of the sampling orifice plate 210.
If the verification is passed, the sampling orifice 210 is placed in a sampling position on the sampling area electronic balance 230.
It should be noted that, the sampling orifice plate 210 may be verified according to the identification result of the identity information of the sampling orifice plate 210 by using a preset verification method. For example, the identification result may be a string text, and whether the sampling aperture plate is verified may be determined by determining whether a character at a specified location (e.g., the 5 th character) in the identification result is a specified character for characterizing the sampling aperture plate 210.
Alternatively, if verification is not passed, the sampling orifice plate 210 may be placed in a waiting area (a particular area in the automated sampling system 10, not shown in FIG. 1) and a prompt may be generated and output for a staff member to troubleshoot if the item being grasped by the robotic arm 260 is not the sampling orifice plate 210.
Through the above-mentioned pre-verification process to the sampling orifice plate 210, it is possible to avoid placing other objects than the sampling orifice plate to the sampling position for sampling, and achieve the fool-proof effect in the sampling process.
In practice, in the process of placing the sampling orifice 210 on the sampling position of the electronic balance 230 by using the mechanical arm 260, the clamping jaw disposed at the front end of the mechanical arm 260 can clamp the sampling orifice 210 to move. For example, the sampling orifice 210 is taken from a refrigerated storage or orifice bin and moved to a sampling position on the sampling area electronic balance 230. However, since the clamping jaw at the front end of the mechanical arm 260 only fixes the sampling orifice plate on the left and right sides, there is no fixing component in the up-down direction and the front-back direction. Here, when the robot arm 260 is parallel to the horizontal plane, a direction (i.e., a left-right direction) perpendicular to the extending direction (i.e., the front-rear direction) of the robot arm 260. Therefore, the robot arm 260 may have an inaccurate positioning problem with respect to the up-down and front-back positions. In particular, the robot arm 260 is stopped in the middle, and there may be a deviation in positioning in the up-down direction and the front-rear direction. The sampling position on the electronic balance 230 of the sampling area is required to be precisely matched with the bottom of the sampling hole plate 210, otherwise, the sampling hole plate 210 may shift, which may cause deviation in positioning of the needle of the subsequent injector into the hole position of the sampling hole plate 210, causing needle to be pricked, the whole system may be blocked, sampling failure occurs, or the sampled fermentation broth enters into the wrong hole position. In order to improve the positioning accuracy of the mechanical arm 260 for placing the sampling orifice plate, the sampling orifice plate 210 may be placed in the secondary positioning area before being placed on the electronic balance of the sampling area, the relative positions between the secondary positioning area and the sampling position on the electronic balance 230 of the sampling area are fixed, and the mechanical arm 260 needs to move the sampling orifice plate 210 from the secondary positioning area to the sampling position on the electronic balance 230 of the sampling area in the left-right direction, and no other direction is needed. Since the positioning of the movement of the arm 260 in the left-right direction is accurate, it is difficult to generate deviation in the process of moving from the secondary positioning area to the sampling position, and thus the arm 260 can precisely place the sampling orifice 210 on the sampling position of the sampling area electronic balance 230.
Specifically, in some alternative embodiments, when the automatic sampling system 10 includes a secondary positioning device (refer to the description of the secondary positioning device above, and not described herein again), in step 5011, the positioning of the sampling orifice 210 in the sampling position on the electronic balance 230 can be performed as follows:
first, the sampling orifice 210 is disposed in the secondary positioning area, and the first outer sidewall 210a and the second outer sidewall 210b of the sampling orifice 210 are detachably abutted to the first inner sidewall 284a and the second inner sidewall 284b of the secondary positioning limiting assembly 284 respectively through the secondary positioning limiting assembly 284.
The sampling aperture plate 210 is then moved from the secondary positioning zone to a sampling location on the sampling zone electronic balance 230.
By adopting the above-described alternative implementation manner of the secondary positioning, the positioning accuracy of the sampling position of the mechanical arm 260 for placing the sampling orifice plate 210 on the sampling area electronic balance 230 can be improved.
In step 5012, the syringe support is located above the sampling orifice plate by the movement of the syringe support moving component, and each syringe is located above the hole site of the sampling orifice plate correspondingly.
In this embodiment, the movement of the syringe support moving assembly 200 can be controlled by the control device 240, and the syringe support 190 is located above the sampling orifice 210 by the movement of the syringe support moving assembly 200, and each syringe is located above the hole site of the sampling orifice 210 correspondingly.
Step 5013, for each fermenter to be sampled, a fermenter sampling operation is performed.
It should be noted that, the sampling sequence between different fermenters to be sampled may be specified in the automatic sampling instruction, or may not be specified. If a sampling sequence is specified, in step 5013, fermenter sampling operations may be performed in the specified sampling sequence between the different fermenters to be sampled; conversely, if the sampling sequence is not specified, the sampling sequence between the different fermenters to be sampled may not be fixed.
Here, the fermenter sampling operation may include steps 50131 to 50138 as shown in FIG. 5C:
And 50131, measuring the mass by using an electronic balance in a sampling area to obtain the pre-sampling mass of the sampling pore plate.
Here, the sample area electronic balance 230 needs to measure the mass before sampling for each fermenter to be sampled to obtain the pre-sampling mass of the sampling orifice 210.
It should be noted that in step 5011, the sampling orifice 210 is already placed at the sampling position above the electronic balance 230 in the sampling area. When step 50131 is first performed in step 5013, no fermentation broth is yet injected into the sampling orifice 210, and the mass weighed at this time is the pre-sampling mass of the sampling orifice 210 for the first fermenter to be sampled. Each subsequent time step 50131 is performed, the mass measured by the sample area electronic balance 230 is directed to the pre-sampling mass of the corresponding fermenter sample aperture plate 210 to be sampled.
It will be appreciated that after the mass is measured by the sample area electronic balance 230 to obtain the pre-sampling mass of the sampling orifice plate 210, the pre-sampling mass of the sampling orifice plate 210 may be sent to the control device 240 for storage. Optionally, the control device 240 may store the pre-sampling quality of the sampling orifice 210 in correspondence with the fermenter identity of the fermenter to be sampled and the operation identity of the present automatic sampling operation (for example, may include a sampling start time), so as to perform statistical analysis on the quality balance and carbon balance of the automatic sampling system 10.
In step 50132, the assembly robot presses the pressing pad on the top of the corresponding syringe of the fermenter to be sampled, so that the corresponding syringe moves downward and the needle tube enters the target hole site of the fermenter to be sampled in the sampling hole plate.
Here, for example, the fermenter to be sampled is fermenter 110, and the corresponding syringe is 114. The fermenter to be sampled is fermenter 120, and the corresponding syringe is 124.
When the hole site in the sampling hole plate 210 is covered with a sealed hole site cover, the injector moves downwards and the needle tube enters the target hole site corresponding to the fermentation tank to be sampled in the sampling hole plate 210, and the needle head at the front end of the needle tube pierces the hole site cover of the target hole site, so that liquid can flow into the target hole site from the needle tube.
Step 50133, open the broth valve of the fermenter to be sampled.
And 50134, starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the target sampling quality corresponding to the fermentation tank to be sampled, and enabling the pumped fermentation liquor to flow into the corresponding target hole site through a corresponding injector.
Because the fermentation liquor valve of the fermentation tank to be sampled is opened, the needle tube of the injector of the fermentation tank to be sampled also enters the target hole site, and after the peristaltic pump of the fermentation tank to be sampled is started, the fermentation liquor of the fermentation tank to be sampled can enter the target hole site through the sampling tube, the fermentation liquor valve, the peristaltic pump and the injector in sequence.
It should be noted that the target sampling volume may be determined by the control device 240 in practice by the target sampling mass and the density of the fermentation broth in the fermenter to be sampled. Then, the purpose of pumping the fermentation liquor with the target sampling volume is achieved by setting the pump speed and the working time length of the peristaltic pump of the fermentation tank to be sampled, and further the fermentation liquor with the target sampling quality is pumped finally.
In practice, the connection between the sampling tube of the fermenter and the peristaltic pump, and between the peristaltic pump and the syringe is through a pipeline (e.g. a silicone tube), and due to the complex pipeline connection, although the valve assembly of the fermenter will not normally leak air, in practice, the applicant has found that as the sampling frequency of the fermentation broth increases, particulate matter in the fermentation broth may become blocked in the pipeline, causing the pipeline to be blocked. In addition, as the sampling times become larger and the service time becomes longer, there is a possibility that the pipe connection may become loose or leak. The blockage, connection looseness or air leakage of the pipeline can not pollute the fermentation liquid in the fermentation tank, but can affect the sampling accuracy. For example, if the pipeline is blocked, the sampled fermentation liquid cannot be pumped into the sampling pore plate, and the pipeline is found to be blocked after inspection, so that the pipeline needs to be replaced. In practice, the use of a disposable pump to pump the broth requires the tubing to be replaced approximately once a week, which results in high cost of purchase of the tubing and labor required to replace the tubing.
In addition, although the pump speed of the peristaltic pump can be set, the actual pumping speed of the peristaltic pump may be different from the set pump speed, and the difference between the actual pump speed and the set pump speed may also cause a decrease in sampling accuracy. In practice, the applicant hopes that peristaltic pumps can achieve a pumping accuracy of 0.1 ml, but peristaltic pumps currently on the market often do not meet this accuracy requirement.
Finally, the volume of each well in sampling orifice plate 210 is limited. For example, for a 48-well sampling well plate, the volume of each well is approximately 4 milliliters. If the peristaltic pump should pump 4 ml of fermentation broth at one time according to the set pump speed and operating time. However, if the actual pumping speed of the peristaltic pump is slightly faster, the actually pumped fermentation liquid may exceed the volume of the hole site in the sampling orifice plate, and the fermentation liquid may overflow from the hole site, thereby polluting other hole sites and causing unreliable sampling of the whole sampling orifice plate. Conversely, if the actual pumping speed of the peristaltic pump is somewhat lower, the actual pumping of fermentation broth into the well site may be insufficient for subsequent analysis operations.
In order to ensure accuracy of quality of the sampled fermentation broth and avoid the problems possibly caused by the higher or lower actual pump speed, in some alternative embodiments, starting the peristaltic pump of the fermentation broth to be sampled may be performed according to the following concept:
The actual pumping speed is determined by sampling a portion of the broth first, rather than taking the target sample mass once, and then based on the mass difference between the broth actually sampled for the first time and the broth mass sampled for the first time. Next, a sub-sampling process is determined based on the actual pump speed.
Specifically, step 50134 may include the following steps 501341 to 501349' as shown in fig. 5D:
and step 501341, determining the first target sampling quality according to the target sampling quality corresponding to the fermentation tank to be sampled.
Here, the first target sampling quality is smaller than the target sampling quality.
Assuming that the target sampling quality corresponding to the fermenter to be sampled is m t, the first target sampling quality is m 1, and specifically, m 1 can be determined according to m t.
In some alternative embodiments, the mass obtained by multiplying the target sampling mass m t corresponding to the fermenter to be sampled by the preset first sampling mass ratio p m1 may be determined as the first target sampling mass m 1. Wherein, the first sampling mass ratio is more than 0 and less than 1. For example, the first sample mass ratio may be 0.5. The equation can be formulated as follows:
m1=mt×p1
In some alternative embodiments, the volume obtained by multiplying the volume V kw of the single sampling aperture in the sampling aperture plate 210 by the preset first sampling volume ratio p v1 may also be determined as the first sampling volume V 1. Here, the preset first sampling volume ratio p v1 is greater than 0 and less than 1, for example, the first sampling volume ratio p v1 may be 0.5. That is, if the first sampling volume p v1 is used to sample and fill the hole site in the sampling orifice 210, there is still room in the hole site for the liquid to be not filled, and the liquid in the hole site does not overflow out of the hole site. Then, the mass obtained by multiplying the density ρ of the fermentation liquid in the fermentation tank to be sampled by the above-mentioned first sampling volume p v1 is determined as the first target sampling mass. The equation can be formulated as follows:
v1=vkw×pv1
m1=ρ×v1
In some alternative embodiments, the mass obtained by multiplying the target sampling mass m t corresponding to the fermentation tank to be sampled by the preset first sampling mass proportion p m1 may be further determined as the first sampling mass m 1,1; the volume obtained by multiplying the volume v kw of each sampling hole site in the sampling hole plate by the preset first sampling volume ratio p v1 is determined as a first sampling volume v 1, and then the mass obtained by multiplying the density ρ of the fermentation broth in the fermentation tank to be sampled by the first sampling volume v 1 is determined as a second sampling mass m 1,2. Finally, the minimum mass of the first sampling mass m 1,1 and the second sampling mass m 1,2 is determined as the first target sampling mass m 1. The equation can be formulated as follows:
m1,1=mt×p1
v1=vkw×pv1
m1,2=ρ×v1
m1=min(m1,1,m1,2)
And 501342, determining the first working time length of the peristaltic pump of the fermentation tank to be sampled according to the first target sampling quality and the preset pump speed.
Here, the first target sampling volume v t1 may be determined by dividing the first target sampling mass m 1 by the fermentation broth density ρ of the fermenter to be sampled. The equation can be formulated as follows:
vt1=m1÷ρ
and then, dividing the first target sampling volume by the duration obtained by the preset pump speed, and determining the first working duration of the peristaltic pump of the fermentation tank to be sampled.
The preset pump speed can be manually set by a professional according to the pump speed working range of the peristaltic pump of the fermentation tank to be sampled, or can be set by adopting a preset pump speed setting rule and can be set within the pump speed working range of the peristaltic pump of the fermentation tank to be sampled. The present disclosure is not particularly limited thereto.
And 501343, starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to a preset pump speed and a first working time.
And 501344, closing a peristaltic pump of the fermentation tank to be sampled.
And 501345, measuring the mass by using an electronic balance in a sampling area to obtain the first sampled mass of the sampling pore plate.
Step 501346, determining a first actual sampling quality based on the pre-sampling quality and the post-first sampling quality of the sampling orifice plate.
It should be noted that, in an ideal case, the first actual sampling quality should be equal to the first target sampling quality. The actual pump speed of the peristaltic pump may be different from the preset pump speed and thus the first actual sampling quality may not be equal to the first target sampling quality.
And step 501347, determining the actual pump speed according to the first actual sampling quality, the first target sampling quality and the preset pump speed.
Specifically, the actual pump speed can be calculated as follows:
First, the ratio of the first actual sampling mass m 1,act divided by the first target sampling mass m t is determined as the actual sampling mass ratio p m,act, which can be expressed as follows:
pm,act=m1,act÷mt
then, the product of the preset pump speed V b,pre multiplied by the actual sampling mass ratio p m,act is determined as the actual pump speed V b,act, which can be expressed specifically by the following formula:
Vb,act=Vb,pre×pm,act
and step 501348, in response to determining that the actual pump speed is less than the preset minimum pump speed, interrupting the fermenter sampling operation, and generating and outputting prompt information for indicating that the pipeline is blocked or the risk of air leakage exists.
If the actual pump speed V b,act is determined to be smaller than the preset minimum pump speed V b,min, namely, V b,act<Vb,min, the pipeline is indicated to have a risk of blockage or air leakage, and error reporting is needed for checking, so that the sampling operation of the fermentation tank can be interrupted, prompt information for indicating that the pipeline is blocked or the risk of air leakage is generated and output, and then a worker can perform fault checking. And after the fault investigation is finished, continuing the sampling operation of the fermentation tank.
And step 501349, in response to determining that the actual pump speed is not less than the preset minimum pump speed and is less than the preset maximum pump speed, determining a secondary sampling working time length based on the actual pump speed and the residual to-be-sampled mass obtained by subtracting the first actual sampling mass from the target sampling mass, and starting a peristaltic pump of the to-be-sampled fermentation tank to pump fermentation liquor according to the preset pump speed and the secondary sampling working time length.
If it is determined that the actual pump speed V b,act is not less than the preset minimum pump speed V b,min and less than the preset maximum pump speed V b,max, i.e., V b,min≤Vb,act<Vb,max, it is indicated that the peristaltic pump is basically operating normally, except that there is a deviation between the actual pump speed and the preset pump speed that is within an acceptable range, so the sub-sampling operation period can be determined as follows:
First, the mass obtained by subtracting the first actual sampling mass m 1,act from the target sampling mass m t is determined as the remaining mass to be sampled m rest.
Then, the volume obtained by dividing the remaining to-be-sampled mass m rest by the density ρ of the fermentation broth of the to-be-sampled fermenter is determined as the remaining to-be-sampled volume v rest, which can be expressed by the following formula:
vrest=mrest÷ρ
finally, the duration obtained by dividing the remaining to-be-sampled volume V rest by the actual pump speed V b,act is determined as the sub-sampling operation duration t 2, and can be specifically expressed by the following formula:
t2=vrest÷Vb,act
After the secondary sampling working time is determined, a peristaltic pump of the fermentation tank to be sampled can be started to pump fermentation liquor according to the preset pump speed and the secondary sampling working time. Here, although the peristaltic pump of the fermenter to be sampled is started according to the preset pump speed, the actual pump speed of the peristaltic pump of the fermenter to be sampled is still the actual pump speed calculated by the above, and therefore, since the sub-sampling operation time is calculated according to the actual pump speed, starting the peristaltic pump of the fermenter to be sampled according to the above manner can obtain the residual fermentation broth of the quality to be sampled by the secondary pump, and thus the fermentation broth of the target sampling quality can be obtained by the total pump.
In step 501349', in response to determining that the actual pumping speed is greater than the preset maximum pumping speed, modifying the pumping speed of the peristaltic pump of the fermenter to be sampled, determining a secondary sampling operation period based on the modified pumping speed and a residual sampling quality obtained by subtracting the first actual sampling quality from the target sampling quality, and starting the peristaltic pump of the fermenter to be sampled to pump the fermentation broth according to the modified pumping speed and the secondary operation sampling period.
If it is determined that the actual pumping speed is greater than the preset maximum pumping speed, i.e., V b,act>Vb,max, it is indicated that the actual pumping speed is too high, and that the liquid in the hole site may overflow to contaminate other hole sites according to the pumping speed, so that the pumping speed of the peristaltic pump of the fermenter to be sampled may be modified in various ways first, and the modified pumping speed is smaller than the preset pumping speed of the peristaltic pump of the fermenter to be sampled. Then, a similar calculation method based on 501349 can be used to determine the sub-sampling operation time based on the modified pump speed and the residual to-be-sampled quality obtained by subtracting the first actual sampling quality from the target sampling quality. And finally, starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the modified pump speed and the secondary working sampling time length.
As an example, the pump speed obtained by multiplying the preset pump speed V b,pre by the preset pump speed ratio p V,bump may be determined as the modified pump speed V b,mod of the peristaltic pump of the fermenter to be sampled. Here, the preset pump speed ratio p V,bump is greater than 0 and less than 1, for example, the preset pump speed ratio may be 0.5. The formula can be expressed as follows:
Vb,mod=Vb,pre×pV,bump
As an example, the pump speed difference obtained by subtracting the preset minimum pump speed V b,min from the preset pump speed V b,pre may also be determined as the modified pump speed V b,mod of the peristaltic pump of the fermenter to be sampled. The formula can be expressed as follows:
Vb,mod=Vb,pre-Vb,min
In some alternative embodiments, the preset pump speed may be a base pump speed of a peristaltic pump of the fermenter to be sampled, and accordingly, the pump speed of the peristaltic pump of the fermenter to be sampled may be modified as follows:
First, the ratio obtained by dividing the first target sampling mass m t by the first actual sampling mass m 1,act is determined as the adjustment pump speed ratio p b,adj, and can be expressed as follows:
pb,adj=mt÷m1,act
Since the actual pump speed V b,act is greater than the preset maximum pump speed V b,max, and accordingly, the first target sampling mass m t is smaller than the first actual sampling mass m 1,act, the pump speed ratio p b,adj is adjusted to be greater than 0 and smaller than 1.
And then, multiplying the preset pump speed by the pump speed after adjusting the pump speed ratio to determine the pump speed after modification of the peristaltic pump of the fermentation tank to be sampled.
Vb,mod=Vb,pre×pb,adj
Because the pump speed ratio p b,adj is adjusted to be larger than 0 and smaller than 1, the modified pump speed V b,mod of the peristaltic pump of the fermentation tank to be sampled is smaller than the original preset pump speed V b,pre, and the speed of the fermentation liquid can be reduced by pumping the fermentation liquid according to the modified pump speed V b,mod, so that the overflow of the fermentation liquid to the hole site is avoided.
According to the applicant's practice, after adopting the alternative implementation mode of sub-sampling, the pipeline can be replaced every week to replace the pipeline once a half year, the pipeline replacement frequency is greatly reduced, and the purchasing cost of the pipeline and the labor cost required for replacement are reduced in reply.
And 50135, closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled.
After the fermentation broth with the target sampling quality is sampled, a fermentation broth valve and a peristaltic pump of the fermentation tank to be sampled can be closed.
And 50136, opening an air valve of the fermentation tank to be sampled to blow the fermentation liquid in the pipeline, peristaltic pump and injector of the fermentation tank to be sampled into the corresponding target hole site.
Through steps 50133 to 50135, a portion of the fermentation broth may still remain in the tube, peristaltic pump and syringe of the fermenter to be sampled, and on the one hand, the remaining fermentation broth is just sampled from the fermenter to be sampled, and is the same as the fermentation broth just injected into the target hole site corresponding to the fermenter to be sampled in the sampling hole plate, and if the remaining fermentation broth is not sampled into the corresponding target hole site in the sampling hole plate, the remaining fermentation broth is wasted. On the other hand, the residual fermentation liquid in the pipeline, peristaltic pump and injector of the fermentation tank may interfere with the next sampling of the fermentation tank.
Therefore, in order to avoid wasting the fermentation broth sampled in real time and avoiding interference to the next sampling of the fermentation tank to be sampled, an air valve of the fermentation tank to be sampled can be opened, and the pipeline, peristaltic pump and residual fermentation broth in the injector of the fermentation tank to be sampled are blown into the target hole site corresponding to the fermentation tank to be sampled in the sampling pore plate by using clean air connected with the other end of the air valve. And 50137, measuring the mass by using an electronic balance in a sampling area to obtain the sampled mass of the sampling pore plate.
Here, the mass measured by the electronic balance in the sampling area is also the mass after sampling of the sampling pore plate for the fermentation tank to be sampled. It can be understood that after the electronic balance in the sampling area measures the mass to obtain the sampled mass of the sampling orifice plate, the sampled mass of the sampling orifice plate can also be sent to the control device for storage.
And step 50138, determining and recording the fermentation liquor sampling quality of the fermentation tank to be sampled based on the pre-sampling quality and the post-sampling quality of the target sampling pore plate, and completing the fermentation tank sampling operation of the fermentation tank to be sampled.
Specifically, the control device may subtract the pre-sampling mass from the post-sampling mass of the sampling orifice for the fermenter to be sampled to obtain the broth sampling mass of the fermenter to be sampled. In this way, data support may be provided for achieving mass balance and carbon balance.
Through step 5013, each fermentation cylinder to be sampled can be sampled, and the sampled fermentation liquor is injected into the corresponding target hole site in the sampling hole plate. Execution of step 5013 may proceed to step 5014 execution.
And 5014, taking away the sampling pore plate to finish the sampling.
After the sampling orifice plate is removed, the sampling orifice plate may be placed in a refrigerated or orifice plate bin, or sent to a verification analysis device for subsequent verification analysis, which is not specifically limited in this disclosure.
By executing the sampling operation in step 501, it is able to automatically sample the fermentation liquor from each fermentation tank to be sampled in the automatic sampling system according to the automatic sampling instruction, and inject the fermentation liquor into the corresponding target hole site of each fermentation tank to be sampled through the peristaltic pump and the injector, and finally the fermentation liquor sample of the fermentation tank to be sampled is stored in the sampling hole plate, so that the fermentation liquor sample can be used for subsequent operations. The above-mentioned in-process is full-automatic completion, can reduce the cost of labor, and from the fermentation broth quality of each fermentation cylinder that waits to take a sample also automatic record, can provide data basis for realizing mass balance and carbon balance.
In the above step 5013, although the air valve of the fermenter to be sampled is opened to blow the fermentation liquid in the pipe, peristaltic pump and syringe of the fermenter to be sampled into the corresponding target hole after sampling in step 50136, referring to fig. 2, it can be seen that air in the process of blowing the air valve open is unable to enter the sampling tube of the fermenter to be sampled, and therefore, some liquid may remain in the sampling tube of the fermenter to be sampled after the sampling operation is performed in step 501. While these residual liquids remain in the sampling tube of the fermenter before the next sampling operation, for the fermenter at that time, which is not already the liquid fermented in real time in the fermenter, the sampling analysis of the residual liquids does not represent the real-time status of the fermenter, and thus, in some alternative implementations, the method flow 500 may further include the following step 502 before the sampling operation is performed in step 501:
step 502, a waste liquid discharge operation is performed.
The waste fluid draining operation may include steps 5021 to 5024 as shown in fig. 5E:
step 5021, placing the waste container in a sampling position on the electronic balance in the sampling area.
Here, the waste liquid container 250 may be manually placed. Alternatively, where the automated sampling system 10 includes a robotic arm 260, the waste container 250 may be placed by the robotic arm 260. It should be noted that a waiting area may be provided in the automatic sampling system 10, from which the waste container 250 may be taken and placed in a sampling position above the sampling area electronic balance 230. In this manner, the waste container 250 and its internal liquid mass can be weighed later.
Similarly, to prevent access to waste container 250 other than waste container 250 (e.g., access to sampling orifice plate 210 or needle wash liquid container 270, etc.), in some alternative embodiments waste container 250 may be provided with an identification code, and automatic sampling system 10 may further include a second identification device 300 disposed in the second identification zone and communicatively coupled to control device 240. Accordingly, in step 5021, the placement of the waste container at the sampling location on the sample area electronic balance can be performed as follows:
First, the waste liquid container 250 is placed in a second identification area corresponding to the second identification device 300 for identification.
For example, the second identification device 300 may be a code scanner or a camera. Accordingly, the identification of the waste liquid container 250 may use the code scanning result of the code scanning gun as the identification result, or the identification result may be obtained by performing image identification on the image shot by the camera.
An instruction may be sent by the control device 240 to the second identification device 300, so that the second identification device 300 performs an identity information collection operation (such as code scanning or photographing, etc.), and feeds back the collected identity information (such as code scanning result or photograph, etc.) to the control device 240. Then, the control device 240 may perform identification according to the identity information fed back by the first identity recognition device 290 to obtain an identity information recognition result of the sampling orifice plate.
Then, the waste liquid container 250 may be verified based on the identification result of the identification information of the waste liquid container 250.
If the verification is passed, the waste container 250 is placed in a sampling position on the sample area electronic balance 230.
It should be noted that, here, the waste liquid container 250 may be verified according to the identification result of the identity information of the second identity recognition device 300 in a preset verification manner. For example, the identification result of the identification information may be a character string text, and then it may be determined whether the authentication of the waste liquid container 250 is passed by determining whether a character at a specified position (for example, the 5 th character) in the identification result of the identification information is a category character for characterizing the waste liquid container 250.
Alternatively, if the verification is not passed, the waste container 250 may be placed in a waiting area (a specific area in the automatic sampling system 10, not shown in fig. 1) and a prompt message indicating that the object grasped by the robot arm 260 is not the waste container 250 may be generated and output for troubleshooting by a worker.
Through the above-mentioned preliminary verification process for the waste liquid container 250, it is possible to avoid placing other objects than the waste liquid container to the sampling position for waste liquid discharge, and to realize a foolproof effect in the waste liquid discharge process.
It should be noted that, in the process of placing the waste liquid container 250 on the sampling position on the electronic balance 230 by the mechanical arm, the positioning accuracy of the mechanical arm for placing the waste liquid container 250 on the sampling position on the electronic balance 230 can be improved by adopting the above-mentioned alternative implementation manner for the secondary positioning in the sampling position on the electronic balance 230.
In step 5022, the syringe holder is positioned above the waste container by the movement of the syringe holder moving assembly, and each syringe can inject liquid into the waste container.
In this embodiment, the movement of the syringe holder moving assembly 200 may be controlled by the control device 240, and the syringe holder 190 may be positioned above the waste container 250 by the movement of the syringe holder moving assembly 200, and each syringe may inject liquid into the waste container 250.
After the execution of step 5022, the process may proceed to step 5023 to continue execution.
Step 5023, for each fermenter to be sampled, a sampling tube waste discharging operation is performed.
It should be noted that, the order of waste liquid discharge between different fermentation tanks to be sampled may be specified in the automatic sampling instruction, or may not be specified. If the waste liquid discharge sequence is specified, in step 5023, the waste liquid discharge operation of the sampling tube may be performed according to the specified waste liquid discharge sequence between different fermentation tanks to be sampled; otherwise, if the waste liquid discharge sequence is not specified, the waste liquid discharge sequence among different fermentation tanks to be sampled may not be fixed.
Here the sample tube waste operation may include steps 50231 to 50235 as shown in FIG. 5F:
in step 50231, the mass of the waste liquid container is obtained by measuring the mass by the electronic balance in the sampling area.
Here, the sample area electronic balance 230 needs to measure the mass before discharging the waste liquid for each fermenter to be sampled to obtain the pre-discharge mass of the waste liquid container 250.
It should be noted that, in step 5021, the waste container 250 is already placed at the sampling position above the electronic balance 230 in the sampling area. When step 50231 is performed for the first time in step 5023, no waste liquid is yet injected into the waste liquid container 250, and the mass obtained by weighing is the mass before sampling for the first fermenter to be sampled in the waste liquid container 250. Each time step 50231 is performed, the mass measured by the electronic balance 230 in the sampling area is obtained for the pre-sampling mass of the waste container 250 of the corresponding fermenter to be sampled.
It will be appreciated that after the sample area electronic balance 230 measures the mass to obtain the pre-draining mass of the waste container 250, the pre-draining mass of the waste container 250 may be sent to the control device 240 for storage. Optionally, the control device 240 may store the pre-sampling quality of the waste liquid container 250 in correspondence with the fermenter identification of the fermenter to be sampled and the operation identification of the present automatic sampling operation (for example, may include a sampling start time), so as to perform statistical analysis on the quality balance and the carbon balance of the automatic sampling system 10.
Alternatively, when a sealing cover is also provided over each accommodation space of the waste liquid container 250, after the step 50231 is performed, the following step 50231' may be further performed:
In step 50231', the assembly robot moves over the syringe support and presses the press pad of the syringe of the fermenter to be sampled so that the syringe of the fermenter to be sampled moves down to the point that the needle is located in the receiving space of the waste container.
That is, the syringe needle of the fermenter to be sampled is caused to pierce the sealing cover of the surface of the waste liquid container, so that the subsequent needle can discharge the liquid into the waste liquid container, via step 50231'. And then proceeds to step 50232.
Step 50232, opens the broth valve of the fermenter to be sampled.
In step 50233, the peristaltic pump of the fermentation tank to be sampled is started to pump the fermentation liquid, and the pumped fermentation liquid flows into the waste liquid container through the corresponding injector.
Here, the maximum waste liquid volume can be determined according to the volume of the sampling tube of the fermentation tank, the volume of the pipeline in the peristaltic pump and the volume of the injector in practice, then the pumping speed and the working time of the peristaltic pump of the fermentation tank to be sampled are set by the control device 240, so as to achieve the purpose of pumping the fermentation liquid with the maximum waste liquid volume, and finally realize the purpose of discharging the waste liquid, so that the fermentation liquid in the sampling tube, the pipeline, the peristaltic pump and the injector is the fermentation liquid from the real-time fermentation in the fermentation tank.
And 50234, closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled.
After the above-mentioned waste liquid discharged from the fermentation tank to be sampled is completed, the fermentation liquid valve and peristaltic pump of the fermentation tank to be sampled can be closed.
And 50235, measuring the mass by an electronic balance in a sampling area to obtain the discharged liquid mass of the waste liquid container.
Here, the mass measured by the sample area electronic balance 230 is also for the post-discharge mass of the waste container 250 for the fermenter to be sampled. It will be appreciated that after the mass is measured by the sample area electronic balance 230 to obtain the post-draining mass of the waste container 250, the post-draining mass of the waste container 250 may also be sent to the control device 240 for storage.
And step 50236, determining and recording the quality of the waste liquid of the sampling tube of the fermentation tank to be sampled based on the quality before and after the liquid discharge of the waste liquid container, and completing the operation of discharging the waste liquid of the sampling tube of the fermentation tank to be sampled.
Specifically, the control device 240 may subtract the pre-tapping mass from the post-tapping mass of the waste container 250 for the fermenter to be sampled to obtain the sampling tube waste mass of the fermenter to be sampled. In this way, data support may be provided for achieving mass balance and carbon balance.
For example, a fermentation zone electronic balance (not shown in FIG. 1) may be provided below each fermenter in the automated sampling system 10, and the mass of the fermenter may be measured under the control of the control apparatus 240. Thus, in order to achieve mass balance and carbon balance, during the execution of the fermenter sampling operation for each fermenter to be sampled in step 5013, before opening the broth valve of the fermenter to be sampled, the following steps 50133' may also be executed:
And step 50133', measuring the mass of the fermentation zone electronic balance which is arranged under the fermentation tank to be sampled to obtain the mass of the fermentation tank to be sampled before sampling.
Here, the control device 240 may control the electronic balance measurement mass of the fermentation area where the fermentation tank to be sampled is disposed to obtain the pre-sampling mass of the fermentation tank to be sampled, and the obtained pre-sampling mass of the fermentation tank to be sampled may be sent to the control device 240 for storage. For example, the pre-sampling quality of the fermenter to be sampled may be stored in correspondence with the identity of the fermenter to be sampled and the identity of the sampling operation.
Based on the alternative implementation of step 50133' described above, the following steps 50237 and 50238 are performed after step 52036:
And 50237, measuring the mass by an electronic balance of a fermentation area arranged under the fermentation tank to be sampled to obtain the mass of the fermentation tank to be sampled.
Here, the control device 240 may control the electronic balance of the fermentation area where the fermentation tank to be sampled is disposed to measure the mass, and the measured mass of the fermentation tank to be sampled may be sent to the control device 240, and then may go to step 50238 to be performed.
And 50238, determining the mass balance information of the fermentation tank to be sampled by the control equipment according to the pre-sampling mass, the fermentation liquid sampling mass, the sampling tube waste liquid mass and the post-sampling mass of the fermentation tank to be sampled.
Here, the control device 240 may first calculate the sum of the fermentation broth sampling quality, the sampling tube waste liquid quality, and the post-sampling quality of the fermentation tank to be sampled as the output quality of the fermentation tank to be sampled.
Then, the difference between the pre-sampling mass and the output mass of the fermenter to be sampled can be calculated as the lost mass of the fermenter to be sampled.
And finally, determining the mass balance information of the fermentation tank to be sampled according to the difference and/or the ratio between the loss mass of the fermentation tank to be sampled and the mass before sampling.
Through step 5023, the waste liquid can be discharged from each fermentation tank to be sampled, the discharged waste liquid is injected into the waste liquid container, and the quality of the waste liquid in the sampling tube of each fermentation tank to be sampled is recorded. And then may proceed to step 5024 execution.
Step 5024, the waste container is removed.
For example, the waste container may be removed manually or by a robotic arm. The waste container can be taken away and placed in a waiting area.
Optionally, the sampling tube waste operation may further include the following step 5025:
step 5025, pouring the liquid in the waste container.
For example, the liquid in the waste liquid container 250 may be poured manually or by the robot arm 260 and placed in the waiting area.
By performing the above step 502 before performing step 501, the last sampled fermentation broth remaining in the sampling tube of the fermenter to be sampled can be drained and filled with the fresh fermentation broth of the fermenter to be sampled at that time. Thus, subsequently in performing step 501, the fermentation broth in the sampling tube of the fermenter to be sampled will be fresh, having substantially the same substances and composition as the fermentation broth in the fermenter to be sampled.
During the execution of step 501, i.e. the sampling operation, although the liquid in the pipeline, peristaltic pump and injector of the fermenter to be sampled is blown into the corresponding target hole site by clean air, some liquid may remain in the pipeline, peristaltic pump or injector of the fermenter, and adhere to the pipe wall to affect the flow rate of the liquid, which may cause the pipe to be blocked, and the liquid may affect the accuracy of the next sampling, so in some alternative implementations, after the execution of the sampling operation of step 501, the method flow 500 may further include the following step 503:
Step 503, performing a pipeline cleaning operation.
Here, the line cleaning operation may include steps 5031 to 5034 as shown in fig. 5G:
Step 5031, placing the waste container in a sampling position on a sample area electronic balance.
Here, the waste container 250 may be placed in the sampling position on the sample area electronic balance 230 after the sampling operation, i.e. after the execution of step 501, either manually or by a robotic arm 260.
It should be noted that, in the process of placing the waste liquid container 250 on the sampling position of the electronic balance 230 by the mechanical arm 260, the positioning accuracy of the mechanical arm 260 for placing the waste liquid container 250 on the sampling position of the electronic balance 230 can be improved by adopting the above-mentioned alternative implementation manner for the secondary positioning in the sampling position of the waste liquid container 250 on the electronic balance 230.
In step 5032, the syringe holder is positioned above the waste container by movement of the syringe holder movement assembly, and each syringe can inject liquid into the waste container.
Here, the specific operation and the technical effects of step 5032 are substantially the same as those of step 5022, and are not described herein.
Step 5033, for each fermenter to be sampled, a fermenter line cleaning operation is performed.
It should be noted that, the automatic sampling instruction may or may not specify a sequence of cleaning the fermenter pipe between the different fermenters to be sampled. If a fermenter pipe cleaning sequence is specified, in step 5033, a fermenter pipe cleaning operation may be performed in accordance with the specified fermenter pipe cleaning sequence between different fermenter to be sampled; otherwise, if the fermenter line cleaning sequence is not specified, the fermenter line cleaning sequence between the different fermenter to be sampled may not be fixed.
Here, the fermenter pipe cleaning operation may include steps 50331 to 50334 as shown in fig. 5H:
optionally, when a sealed cap is also provided over each accommodation space of the waste liquid container 250, the following step 50331' may also be performed before performing step 50331:
in step 50331', the assembly robot moves over the syringe holder and presses the press pad of the syringe of the fermenter to be sampled, so that the syringe of the fermenter to be sampled moves down to the point that the needle is located in the accommodation space of the waste container.
That is, the syringe needle of the fermenter to be sampled is caused to pierce the sealing cover of the surface of the waste liquid container 250 so that the subsequent needle can discharge the liquid into the waste liquid container 250, via step 50331'. And then proceeds to step 50331.
Step 50331, opening the cleaning liquid valve of the fermenter to be sampled.
Step 50332, starting a peristaltic pump of the fermentation tank to be sampled to pump cleaning liquid, cleaning a pipeline, the peristaltic pump and an injector of the fermentation tank to be sampled, and enabling the cleaned cleaning liquid to flow into a waste liquid container from the injector of the fermentation tank to be sampled.
Since the liquid in the pipeline, peristaltic pump and injector of the fermenter to be sampled is blown into the corresponding target hole site by clean air after the step 501 is performed, i.e. during the sampling operation, some liquid may remain in the pipeline, peristaltic pump or injector of the fermenter to be sampled, and adhere to the pipe wall to affect the flow rate of the liquid, which may cause the pipeline to be blocked, and may affect the detection accuracy of the next sampling. Therefore, residual liquid in a pipeline, a peristaltic pump and an injector of the fermentation tank to be sampled can be taken away by utilizing the flow of the cleaning liquid, so that the pipeline is prevented from being blocked, and the cross influence of fermentation liquid can be placed. In addition, the pipeline, peristaltic pump and injector of the fermentation tank to be sampled can be disinfected and sterilized by the cleaning liquid, so that the breeding of bacteria is prevented.
Here, the maximum flow volume of the fermentation broth during sampling can be determined according to the volume of the fermentation tank pipeline, the volume of the pipeline in the peristaltic pump and the volume of the injector in practice. The control device 240 then determines the volume of cleaning fluid required based on the maximum flow volume of the broth sample process described above. Finally, the pump speed and the working time length of the peristaltic pump of the fermentation tank to be sampled are set according to the required cleaning liquid volume, so that the purpose of pumping the cleaning liquid with the required cleaning liquid volume is achieved, and further the pipeline, the peristaltic pump and the injector of the fermentation tank to be sampled are finally cleaned and disinfected. Alternatively, the volume of cleaning fluid required may be greater than the maximum flow-through volume of the broth sampling process. For example, the volume of cleaning fluid required may be five times the maximum flow volume of the broth sampling process to achieve adequate cleaning and disinfection.
And 50333, closing a cleaning liquid valve of the fermentation tank to be sampled.
After the fermentation tank to be sampled is subjected to pipeline cleaning, a cleaning liquid valve of the fermentation tank to be sampled can be closed.
And 50334, opening an air valve of the fermentation tank to be sampled so as to blow residual liquid in a pipeline, a peristaltic pump and an injector of the fermentation tank to be sampled into a waste liquid container, and completing the fermentation tank pipeline cleaning operation of the fermentation tank to be sampled.
Here, the air valve is connected to clean air after filtration, and specifically, an air filtration membrane (for example, an air filtration membrane of 0.22 μm) may be connected to the rear end of the air valve, and the air filtration membrane may remove the bacteria in the air.
Through step 5033, the residual liquid in the pipeline, peristaltic pump and injector of each fermenter to be sampled can be cleaned, disinfected and dried to prevent the pipeline from being blocked and the bacteria from growing, and the waste liquid container is filled with cleaning liquid, and then the process can be carried out in step 5034.
Step 5034, the waste container is removed.
For example, the waste container may be removed manually or by a robotic arm. The waste container can be taken away and placed in a waiting area.
Optionally, the line cleaning operation may further include the following step 5035:
Step 5035, pouring the liquid in the waste liquid container.
For example, the liquid in the waste liquid container can be poured manually or by a mechanical arm and then placed in the waiting area.
In some alternative embodiments, the line cleaning operation may further include the following step 5031' prior to step 5031:
In step 5031', the mass is measured by the sample area electronic balance to obtain the pre-cleaning mass of the waste liquid container pipeline.
And, after step 5033, before step 5034, may further include the following step 5034':
In step 5034', the electronic balance in the sampling area measures the mass to obtain the mass after the pipeline cleaning of the waste liquid container, and the difference of the mass after the pipeline cleaning of the fermentation tank to be sampled is determined and recorded based on the mass before the pipeline cleaning of the waste liquid container and the mass after the pipeline cleaning.
Here, the poor quality of the line cleaning of the fermenter to be sampled, recorded by steps 5031 'and 5034', is not used for the calculation of the mass balance or carbon balance, but is used to verify whether the automatic sampling system is operating properly, because the line cleaning operation of step 503 is only used to clean away the part of the residual fermentation broth attached to the line, preventing cross contamination and line blockage, and the part of the fermentation broth remains very little.
Since the needle of each syringe is exposed to the air, and there may be foreign bacteria in the air, the needle may be contaminated with the foreign bacteria in the air. To ensure that the needle does not contaminate the sampling orifice 210 and the fermentation broth in the sampling orifice 210, in some alternative embodiments, the automated sampling method flow 500 may further include the following step 504 prior to performing the waste discharge operation, i.e., prior to performing step 502:
At step 504, a needle cleaning operation is performed.
Here, the needle cleaning operation may include steps 5041 and 5042 as shown in fig. 5I:
In step 5041, each syringe needle received by the syringe support is received in the needle wash liquid container through the top opening of the needle wash liquid container by movement of the syringe support movement assembly so that each syringe needle is washed by the received wash liquid.
For example, movement of syringe carrier movement assembly 200 may be controlled by control device 240 to cause syringe carrier 190 to move downwardly and to cause each syringe needle received by syringe carrier 190 to be received within needle wash liquid container 270 through the top opening of needle wash liquid container 270 for washing each syringe needle with the contained wash liquid.
In step 5042, each syringe needle received by the syringe support is moved away from the needle wash liquid container by movement of the syringe support movement assembly.
For example, syringe support 190 may be moved upward by movement of syringe support movement assembly 200 until the needle of each syringe is a distance from the top of needle cleaning solution container 270 that may allow removal of needle cleaning solution container 270 without contacting the needle of each syringe.
Step 5043, removing the needle cleaning fluid container.
For example, the needle cleaning fluid reservoir may be removed manually or by a robotic arm. The needle cleaning liquid container can be taken out and placed in a waiting area.
Optionally, step 504 may further include the following step 5044:
step 5044, pour the liquid in the needle wash container.
For example, the liquid in the waste liquid container can be poured manually or by a mechanical arm and then placed in the waiting area.
In some alternative embodiments, the needle cleaning operation may further comprise the following step 5041' prior to step 5041:
step 5041', placing the needle cleaning fluid container in a sampling position on the sample area electronic balance.
Therefore, the required space for the needle cleaning liquid to be arranged in the needle cleaning process is not needed, and the space required by the automatic sampling system is saved only by placing the needle cleaning liquid in the sampling position on the electronic balance in the sampling area.
In some alternative embodiments, after performing step 503, i.e., performing the line cleaning operation, the method further comprises the step 505 of:
step 505, the needle cleaning operation is performed again.
After step 505 is performed, i.e. during the process of performing the pipeline cleaning operation, the needle of each syringe is exposed to the air, which may cause contamination of the needle by the bacteria in the air, so that the needle needs to be cleaned and disinfected in time to avoid contamination of the bacteria.
In some alternative embodiments, each line connecting the valve assemblies (including the broth valve, air valve, and rinse liquid valve) may be connected to the rinse liquid container prior to the first sampling, i.e., prior to the first execution of step 501, and then each valve assembly and peristaltic pump may be opened to allow the rinse liquid to flow through each valve assembly, peristaltic pump, syringe, and corresponding line in sequence and be injected into the waste liquid container 250 for the first line rinse. And then, the pipeline connecting structure of each valve assembly is restored to the original state. Thus, the valve components, peristaltic pumps, syringes and pipelines of each fermentation tank can be cleaned and sterilized.
The automatic sampling method provided by the above-described embodiments of the present disclosure can achieve automatic sampling by the mutual cooperation of the respective components in the automatic sampling system 10, reduce labor costs, and can help achieve mass balance and carbon balance by weighing the sampling orifice plate 210 with poor quality before and after sampling.
As another aspect, the present disclosure also provides a control apparatus including: one or more processors; a storage device having one or more programs stored thereon that, when executed by the one or more processors, cause the automatic sampling system described in connection with the embodiment shown in fig. 1 and its alternative embodiments to implement the method described in connection with fig. 5A and its alternative embodiments.
As another aspect, the present disclosure also provides a computer-readable storage medium having stored thereon a computer program, wherein the computer program, when executed by one or more processors, causes an automatic sampling system as described in the embodiment shown in fig. 1 and its alternative embodiments to implement a method as described in fig. 5A and its alternative embodiments.
As another aspect, the present disclosure also provides a computer program product comprising computer programs/instructions which, when executed by a processor, cause an automatic sampling system as described in the embodiment shown in fig. 1 and its alternative embodiments to implement a method as described in fig. 5A and its alternative embodiments.
The flowcharts and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present disclosure. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems which perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
Furthermore, each functional module in the embodiments of the present disclosure may be integrated in one processing unit, or each module may exist alone physically, or two or more modules may be integrated in one processing unit. The integrated processing unit may be implemented in hardware or in software functional modules. The integrated processing unit may also be stored in a computer readable storage medium if implemented in the form of a software functional unit and sold or used as a stand alone product.
The foregoing description is only of the preferred embodiments of the present disclosure and description of the principles of the technology being employed. It will be appreciated by those skilled in the art that the scope of the invention referred to in this disclosure is not limited to the specific combination of features described above, but encompasses other embodiments in which features described above or their equivalents may be combined in any way without departing from the spirit of the invention. Such as those described above, are mutually substituted with the technical features having similar functions disclosed in the present disclosure (but not limited thereto).

Claims (21)

1. An automatic sampling system, comprising:
The fermentation device comprises at least one fermentation tank, wherein a sampling tube is arranged inside each fermentation tank, a valve assembly, a peristaltic pump and a syringe are arranged outside each fermentation tank, the sampling tube of each fermentation tank is sequentially communicated with the corresponding valve assembly, peristaltic pump and syringe through pipelines, the valve assembly comprises a fermentation liquor valve, an air valve and a cleaning fluid valve, one ends of the fermentation liquor valve, the air valve and the cleaning fluid valve are respectively communicated with the corresponding peristaltic pumps, and the other ends of the fermentation liquor valve, the air valve and the cleaning fluid valve are respectively communicated with the sampling tube, the air source and the cleaning fluid container of the corresponding fermentation tank;
the syringe brackets are used for accommodating syringes corresponding to the fermentation tanks, the top of each syringe is provided with a pressing pad, the bottom of each syringe is provided with a needle, and the needle is vertically arranged in an accommodating hole of each syringe bracket downwards;
A syringe support moving assembly for moving the syringe support in a plane and up and down, the syringe support being fixed to the syringe support moving assembly;
a sampling orifice plate having at least one aperture for receiving a liquid;
The assembly robot is used for moving to the upper part of the syringe bracket and pressing the pressing pad of the syringe so that the syringe moves downwards to the position that the needle is positioned in the hole site of the sampling pore plate;
the electronic balance of the sampling area is arranged in the sampling area and used for weighing the mass in the sampling process;
The control equipment is in communication connection with each valve assembly, each peristaltic pump, the syringe support moving assembly, the assembly robot and the sampling area electronic balance; and
A waste liquid container for containing liquid.
2. The automated sampling system of claim 1, wherein the assembly robot is a selective compliant assembly robot arm.
3. The automatic sampling system of claim 1, wherein a respective fermentation zone electronic balance is provided below each fermenter, the fermentation zone electronic balance being used to weigh the mass of the fermenter above.
4. The automatic sampling system of claim 1, wherein the automatic sampling system further comprises:
The mechanical arm is used for clamping and moving the sampling pore plate; preferably, the mechanical arm is further used for clamping and moving the waste liquid container.
5. The automatic sampling system of claim 1, wherein the automatic sampling system further comprises:
And a needle cleaning liquid container having an opening formed above, through which a needle can be accommodated in the needle cleaning liquid container when each of the syringes is placed in the syringe holder, for cleaning the needle of each of the syringes by the accommodated cleaning liquid.
6. The automatic sampling system of claim 4, wherein the sampling area electronic balance is provided with a subject positioning structure matching the bottom of the sampling orifice plate, the subject positioning structure being configured to detachably fix the sampling orifice plate, the mechanical arm front end being provided with a clamping jaw along a first direction, the automatic sampling system further comprising:
The secondary positioning device is arranged in a secondary positioning area and comprises a first control valve, a second control valve, a position sensor and a secondary positioning limiting assembly, the first control valve and the second control valve are used for moving according to position information detected by the position sensor, so that adjacent first outer side walls and second outer side walls of the sampling pore plate are respectively detachably abutted to the first inner side wall and the second inner side wall of the secondary positioning limiting assembly, an intersection point between horizontal projection of the first inner side wall and horizontal projection of the second inner side wall of the secondary positioning limiting assembly is a reference positioning point, a preset sampling positioning point in horizontal projection of a measured object positioning structure is fixed with a relative position between the reference positioning point, and the mechanical arm can move along the first direction only from the reference positioning point to reach the preset sampling positioning point.
7. The automatic sampling system of claim 1, wherein the syringe comprises:
The needle tube comprises a needle head and a needle tail;
The lower end of the connecting pipe is detachably communicated with the needle tail;
the pipeline connecting piece is hollow, the lower end of the pipeline connecting piece is detachably communicated with the upper end of the connecting pipe, the upper end of the pipeline connecting piece is communicated with an output pipeline of the syringe corresponding to the peristaltic pump, and the outer wall of the pipeline connecting piece is provided with a groove;
The lower end of the needle tube feeding support is in an open arrangement, the connecting tube and the pipeline connecting piece are arranged in the needle tube feeding support, the needle tube feeding support is provided with a clamping structure, the clamping structure is matched with and embedded in a groove arranged on the outer wall of the pipeline connecting piece, a pipeline inlet is formed in the side wall of the needle tube feeding support, and an output pipeline of the injector corresponding to the peristaltic pump can pass through the pipeline inlet from the outside of the needle tube feeding support and enter the inside of the needle tube feeding support;
the push rod is fixedly arranged at the upper end of the needle feeding bracket;
the pressing pad is fixedly arranged at the upper end of the push rod;
The spring is sleeved outside the push rod, the upper end and the lower end of the spring are respectively abutted to the pressing pad and the needle tube feeding support, and the spring is used for enabling the whole injector to move upwards.
8. The automatic sampling system of claim 1, wherein the sampling aperture plate is provided with an identification code, the automatic sampling system further comprising:
the first identity recognition device is arranged in the first identity recognition area and is in communication connection with the control device;
preferably, the waste liquid container is provided with an identification code, and the automatic sampling system further comprises:
the second identity recognition device is arranged in the second identity recognition area and is in communication connection with the control device.
9. An automatic sampling method applied to the automatic sampling system according to any one of claims 1 to 8, the method comprising:
Performing a sampling operation, the sampling operation comprising:
placing the sampling pore plate in a sampling position above the electronic balance of the sampling area;
the injector support is positioned above the sampling pore plate through the movement of the injector support moving assembly, and each injector is respectively and correspondingly positioned above the hole site of the sampling pore plate;
For each fermenter to be sampled, the following fermenter sampling operation is performed: the electronic balance of the sampling area measures the mass to obtain the mass before sampling of the sampling pore plate; the assembling robot presses a pressing pad at the top of the injector corresponding to the fermentation tank to be sampled, so that the corresponding injector moves downwards and the needle tube enters a target hole site corresponding to the fermentation tank to be sampled in the sampling pore plate; opening a fermentation liquor valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the target sampling quality corresponding to the fermentation tank to be sampled, and enabling the pumped fermentation liquor to flow into the corresponding target hole site through a corresponding injector; closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled; opening an air valve of the fermentation tank to be sampled so as to blow a pipeline of the fermentation tank to be sampled, a peristaltic pump and fermentation liquor in an injector into a corresponding target hole site; the electronic balance of the sampling area measures the mass to obtain the sampled mass of the sampling pore plate; determining and recording the fermentation liquor sampling quality of the fermentation tank to be sampled based on the pre-sampling quality and the post-sampling quality of the target sampling pore plate, and completing the fermentation tank sampling operation of the fermentation tank to be sampled;
and taking away the sampling pore plate to finish the sampling.
10. The automatic sampling method according to claim 9, wherein, prior to performing the sampling operation, the method further comprises performing a waste fluid discharge operation, the waste fluid discharge operation comprising in particular:
placing the waste liquid container at a sampling position on the electronic balance of the sampling area;
Positioning the syringe support above the waste container by movement of the syringe support movement assembly, and each syringe being operable to inject liquid into the waste container;
For each fermenter to be sampled, the following sampling tube waste discharge operation was performed: the electronic balance of the sampling area measures the mass to obtain the pre-liquid-discharge mass of the waste liquid container; opening a fermentation liquor valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor, and enabling the pumped fermentation liquor to flow into the waste liquid container through a corresponding injector; closing a fermentation liquor valve and a peristaltic pump of the fermentation tank to be sampled; the electronic balance of the sampling area measures the mass to obtain the discharged liquid mass of the waste liquid container; determining and recording the quality of the waste liquid of the sampling tube of the fermentation tank to be sampled based on the quality before and after the liquid discharge of the waste liquid container, and completing the operation of discharging the waste liquid of the sampling tube of the fermentation tank to be sampled;
Removing the waste liquid container;
preferably, pouring the liquid in the waste liquid container is also included.
11. The automatic sampling method of claim 10, wherein after performing the sampling operation, the method further comprises: executing a pipeline cleaning operation, wherein the pipeline cleaning operation specifically comprises the following steps:
placing the waste liquid container at a sampling position on the electronic balance of the sampling area;
Positioning the syringe support above the waste container by movement of the syringe support movement assembly, and each syringe being operable to inject liquid into the waste container;
For each fermenter to be sampled, the following fermenter line cleaning operation is performed: opening a cleaning liquid valve of the fermentation tank to be sampled; starting a peristaltic pump of the fermentation tank to be sampled to pump cleaning liquid, and cleaning a pipeline, the peristaltic pump and the injector of the fermentation tank to be sampled, wherein the cleaned cleaning liquid flows into the waste liquid container from the injector of the fermentation tank to be sampled; closing a cleaning liquid valve of the fermentation tank to be sampled; opening an air valve of the fermentation tank to be sampled so as to blow residual liquid in a pipeline, a peristaltic pump and an injector of the fermentation tank to be sampled into the waste liquid container, and completing the fermentation tank pipeline cleaning operation of the fermentation tank to be sampled;
Removing the waste liquid container;
Preferably, further comprising pouring the liquid in the waste liquid container;
Preferably, in the fermenter pipe cleaning operation, before opening the cleaning liquid valve of the fermenter to be sampled, the method further includes: the electronic balance of the sampling area measures the mass to obtain the mass of the waste liquid container before the pipeline is cleaned; and after opening an air valve of the fermenter to be sampled to empty the remaining liquid in the pipe of the fermenter to be sampled, further comprising: and the electronic balance in the sampling area measures the mass to obtain the mass after the pipeline cleaning of the waste liquid container, and determines and records the pipeline cleaning mass difference of the fermentation tank to be sampled based on the mass before the pipeline cleaning of the waste liquid container and the mass after the pipeline cleaning.
12. The automatic sampling method according to claim 11, wherein, prior to performing the waste fluid discharge operation, the method further comprises performing a needle cleaning operation, the needle cleaning operation comprising in particular:
Causing each of the syringe needles accommodated by the syringe holder to be accommodated in the needle cleaning liquid container through a top opening of the needle cleaning liquid container by movement of the syringe holder moving assembly so as to be cleaned by the accommodated cleaning liquid;
Causing each of said syringe needles received by said syringe carrier to leave said needle wash liquid container by movement of said syringe carrier movement assembly;
Removing the needle cleaning liquid container;
preferably, further comprising pouring the liquid in the needle cleaning liquid container;
Preferably, in the needle cleaning operation, before each of the syringe needles accommodated in the syringe holder is accommodated in the needle cleaning solution container through the top opening of the needle cleaning solution container by the movement of the syringe holder moving assembly, further comprising: and placing the needle head cleaning liquid container at a sampling position on the electronic balance in the sampling area.
13. The automatic sampling method of claim 12, wherein after performing the line purging operation, the method further comprises: the needle cleaning operation is performed again.
14. The automatic sampling method according to claim 9, wherein the starting the peristaltic pump of the fermentation tank to be sampled pumps the fermentation liquid according to the target sampling quality corresponding to the fermentation tank to be sampled, comprising:
Determining first target sampling quality according to the target sampling quality corresponding to the fermentation tank to be sampled, wherein the first target sampling quality is smaller than the target sampling quality;
determining the first working time length of a peristaltic pump of the fermentation tank to be sampled according to the first target sampling quality and a preset pump speed;
Starting a peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the preset pump speed and the first working time;
closing a peristaltic pump of the fermentation tank to be sampled;
the electronic balance of the sampling area measures the mass to obtain the first sampled mass of the sampling pore plate;
Determining a first actual sampling quality based on a pre-sampling quality and a first post-sampling quality of the sampling orifice plate;
determining an actual pump speed according to the first actual sampling quality, the first target sampling quality and the preset pump speed;
In response to determining that the actual pump speed is less than a preset minimum pump speed, interrupting the fermenter sampling operation, generating and outputting prompt information for indicating that there is a risk of pipeline blockage or air leakage;
In response to determining that the actual pump speed is not less than a preset minimum pump speed and is less than a preset maximum pump speed, determining a secondary sampling working time length based on the actual pump speed and a residual to-be-sampled mass obtained by subtracting the first actual sampling mass from the target sampling mass, and starting a peristaltic pump of the to-be-sampled fermentation tank to pump fermentation liquor according to the preset pump speed and the secondary sampling working time length;
And in response to determining that the actual pump speed is greater than a preset highest pump speed, modifying the pump speed of the peristaltic pump of the fermentation tank to be sampled, determining a secondary sampling working time length based on the modified pump speed and the residual sampling quality obtained by subtracting the first actual sampling quality from the target sampling quality, and starting the peristaltic pump of the fermentation tank to be sampled to pump fermentation liquor according to the modified pump speed and the secondary working sampling time length.
15. The automatic sampling method of claim 9, wherein the method further comprises:
Before the first sampling, connecting each pipeline connected with each valve component to the cleaning liquid container, opening each valve component and each peristaltic pump to enable the cleaning liquid to sequentially flow through each valve component, the peristaltic pump, the injector and the corresponding pipeline, and injecting the cleaning liquid into the waste liquid container for the first pipeline cleaning;
And restoring the pipeline connecting structure of each valve assembly.
16. The automatic sampling method of claim 9, wherein the sampling aperture plate is provided with an identification code, the automatic sampling system further comprising a first identification device disposed in a first identification zone and communicatively coupled to the control device; and
The placing the sampling pore plate at the sampling position on the sampling area electronic balance comprises the following steps:
Placing the sampling pore plate in a first identification area corresponding to first identification equipment for identification;
And responding to the verification passing of the sampling pore plate according to the identification result of the identity information of the sampling pore plate, and placing the sampling pore plate in a sampling position on the electronic balance of the sampling area.
17. The automatic sampling method according to claim 10 or 11, wherein the waste liquid container is provided with an identification code, the automatic sampling system further comprising a second identification device provided in a second identification zone and in communication with the control device; and
The placing the waste liquid container at a sampling position on the sampling area electronic balance comprises the following steps:
placing the waste liquid container in a second identity recognition area corresponding to second identity recognition equipment for identity recognition;
And responding to the verification passing of the waste liquid container according to the identification result of the identity information of the waste liquid container, and placing the waste liquid container at a sampling position on the electronic balance of the sampling area.
18. The automatic sampling method according to claim 9, wherein the automatic sampling system further comprises a secondary positioning device arranged in the secondary positioning area, the secondary positioning device comprises a first control valve, a second control valve, a position sensor and a secondary positioning limiting assembly, at least two adjacent outer side walls of the sampling orifice plate can be matched with the inner structural wall of the secondary positioning limiting assembly, and the first control valve and the second control valve are used for moving according to the position information detected by the position sensor so as to enable at least two adjacent outer side walls of the sampling orifice plate to be detachably abutted against the inner structural wall of the secondary positioning limiting assembly; and
The placing the sampling pore plate at the sampling position on the sampling area electronic balance comprises the following steps:
Placing the sampling pore plate in a secondary positioning area, and performing secondary positioning on the sampling pore plate through the secondary positioning device;
And moving the sampling pore plate from the secondary positioning area to a sampling position on the electronic balance of the sampling area.
19. A control apparatus comprising:
one or more processors;
a storage device having one or more programs stored thereon,
The one or more programs, when executed by the one or more processors, cause the automatic sampling system of any of claims 1-8 to implement the method of any of claims 9-18.
20. A computer readable storage medium having stored thereon a computer program, wherein the computer program, when executed by one or more processors, causes the automatic sampling system of any of claims 1-8 to implement the method of any of claims 9-18.
21. A computer program product comprising computer programs/instructions which, when executed by a processor, cause an automatic sampling system according to any one of claims 1-8 to implement a method according to any one of claims 9-18.
CN202410087787.3A 2024-01-22 2024-01-22 Automatic sampling system, method and related products Pending CN118090321A (en)

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Application Number Priority Date Filing Date Title
CN202410087787.3A CN118090321A (en) 2024-01-22 2024-01-22 Automatic sampling system, method and related products

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