CN103305420A - Small-size in-vitro cell culture measuring and control device - Google Patents
Small-size in-vitro cell culture measuring and control device Download PDFInfo
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- CN103305420A CN103305420A CN201310233269XA CN201310233269A CN103305420A CN 103305420 A CN103305420 A CN 103305420A CN 201310233269X A CN201310233269X A CN 201310233269XA CN 201310233269 A CN201310233269 A CN 201310233269A CN 103305420 A CN103305420 A CN 103305420A
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Abstract
The invention discloses a small-size in-vitro cell culture measuring and control device which comprises a cell culture micro-chamber unit, an environment parameter acquisition unit, a singlechip processing unit, a feedback adjusting unit and a remote interaction unit. According to the small-size in-vitro cell culture measuring and control device disclosed by the invention, by utilizing feedback control, the continuous detection on cell activity in a culture process is realized; the cell culture micro-chamber unit is machined by a light-transmitting acrylic material, the manufacturing of small-size in-vitro culture utensils is realized, the specific shapes of the small-size in-vitro culture utensils can be customized according to demands, and the utensils are convenient to machine and simple to sterilize; the informatization of a culture device is realized, the environment is monitored in the culture process, and the environment stabilization is kept and at the same time the traceability of experimental data is improved; the functions of remote interaction, abnormal state alarming, remote checking, remote control and the like are achieved.
Description
Technical field
The cells in vitro that the present invention relates to a kind of miniaturization is cultivated measuring and control device, can realize the continuous detecting of cellular activity in the culturing process.
Background technology
Current, life science has developed into cell and molecular level, scientists begins to focus on fields such as the internal activity, signal conduction, cell-cell interaction of biological cell, they utilize a series of advanced persons' such as electromagnetism, optics, mechanics method that unicellular or cell mass are detected, and these new detection techniques need rely on continuously reliable cell in vitro culture apparatus to assist.
Traditional cell in vitro culture apparatus is with CO
2Incubator is main representative, and its advantage is accurately to control temperature, humidity and the CO of cell growth
2Parameters such as concentration, the control accuracy height, environmental perturbation is little, is applicable to that the cells in vitro of nearly all type is cultivated.The advanced equipment of part has the function of computer control and remote alarms.But CO on the whole,
2Incubator is bulky, and stronger stopping property requirement is arranged, and can not be applicable to the long-time online detection of cell.
The cell culture apparatus with continuous detecting function that some are novel is in recent years also invented successively, and most widely used is the minicell vitro culture device that uses in the viable cell workstation.This apparatus features is that volume is little, transparence is high, can combine with inverted biologic microscope, is applicable to continuous fluoroscopic examination.But functions such as its defective is that device reliability is general, the monitoring record of sterilization difficulty height, environmental parameter and remote alarms control still are unrealized.
Summary of the invention
Goal of the invention: in order to overcome the deficiencies in the prior art, the cells in vitro that the invention provides a kind of miniaturization is cultivated measuring and control device, realizes the continuous detecting of cellular activity in the culturing process, and can record the culturing process environmental parameter, is convenient to experimental analysis.
Technical scheme: for achieving the above object, the technical solution used in the present invention is:
A kind of cells in vitro of miniaturization is cultivated measuring and control device, comprises cell cultures microchamber unit, environmental parameter collecting unit, micro-chip processing unit and feedback regulation unit:
Described cell cultures microchamber unit provides the space for the placement of cell culture container;
Described environmental parameter collecting unit is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration detects and detection information is sent to the micro-chip processing unit;
Described micro-chip processing unit is handled, is stored and show the information that receives, and produces the feedback regulation signal and sends to the feedback regulation unit;
The information that described feedback regulation unit basis receives is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration is regulated.
Preferably, described cell cultures microchamber unit comprises box body and top cover, and described box body is printing opacity acrylic material, and described top cover is the heating glass material, and the inside of described box body is provided with a circle tank, and the sidewall of described box body is provided with CO
2Ventilating pit.Described box body can customize according to the real needs that detect, reaching the purpose with other monitoring device couplings, convenient for production and cultivate before pre-treatment such as sterilization all comparatively simple.The design of tank mainly contains two functions: the one, for humidification provides the water source, under the situation of heat supply, guarantee the high humidity in the box body; The 2nd, play insulation effect, because that specific heat of water holds is bigger, the ability of storing heat is more intense, water filling helps to reduce the temperature degree of disturbing in the box body in tank.Top cover adopts heating glass processing, also can keep transparence preferably when heating function is provided, is convenient to observe.CO
2The design of ventilating pit is the CO that regulates for convenience in the box body
2Gas concentration.The top cover of tank, heating glass and CO
2Ventilating pit has constituted the major portion of feedback regulation unit jointly, to guarantee the ambient stable in the box body.
More preferred, be provided with the silica gel hot-plate in the described box body, realize heating function jointly by silica gel heat block and heating glass top cover; The size of its heating power can realize by the resistance of regulating voltage and heater element; By certain algorithm heating power and heat-up time are controlled, just can be realized the temperature in the box body.
Preferably, described environmental parameter collecting unit comprises Temperature Humidity Sensor and CO
2Sensor.Because the structure of cell cultures microchamber unit is less, when design, also should select the less sensor of volume for use; Simultaneously, cell cultures is higher for environment requirement, and measured parameter is also had higher accuracy requirement; Consider that based on above-mentioned two aspects described Temperature Humidity Sensor adopts DHT22 Temperature Humidity Sensor, described CO
2Sensor adopts the infrared non-spectral CO of SRH-5
2Sensor.The DHT22 Temperature Humidity Sensor can detect relative humidity and temperature simultaneously, and signal is calibration and digitizing output all, precision good (temperature ± 0.1 ℃, humidity ± 0.1%RH), meet user demand.The infrared non-spectral CO of SRH-5
2Therefore signal of sensor is simulating signal, need carry out A/D and be converted to numerary signal and can store and handle.
Consider that the cell in vitro culture environment can influence cell in external production process, therefore, after the environmental parameter of finishing inside, cell cultures microchamber unit is gathered, need store, handle and show these data, help the user that the change procedure of integrated environment in system's operational process is comprehensively understood, help experimental result is analyzed.Based on the micro-chip processing unit, can also derive and design other auxiliary units, such as demonstration, warning device, upper computer connection and the remote interaction unit etc. of chart.
The transmission of degree signal, parameter storage and parameter showed three parts in real time before the micro-chip processing unit mainly comprised.
Can be to temperature, humidity and CO by LED display
2Concentration shows, because the data that micro-chip obtains are the value of integer (inaccurate), therefore need carry out the algorithm correction to the data that micro-chip obtains; In addition, because the storage unit in the micro-chip is less, and readjustment historical data difficulty, so the data transmission after can utilizing serial ports with front-end collection is stored to upper computer; In order to raise the efficiency, reduce the number of times of data transmission, when micro-chip carries out data transmission to upper computer, at first need the pre-treatment of encoding, with temperature, humidity and CO
2Three groups of data integration of concentration are that one group of data transfers to upper computer again.
Decoding, storage and the display operation that adopts upper computer to carry out data can reduce the burden of micro-chip and the affinity that personnel use.Carry out software programming by MFC and can easily realize correlation function, the function that generally needs upper computer to realize by software comprises: 1, obtain the data that micro-chip transmits and decode, 2, the data and the chart that dynamically show transmission, 3, carry out the selection of serial ports attribute, 4, the storage of data.For data and chart, data are used for the real-time numerical value of display environment parameter, and chart is X-coordinate with time, draw the time dependent performance graph of each environmental parameter.
Described micro-chip processing unit carries out information interaction by remote interaction unit and remote service end; Preferably, described remote interaction unit is TC35 series double frequency 900/1800MHZ integrated GSM module, and this gsm module carries the RS232 communication interface, can carry out on-line communication with PC or micro-chip easily.Micro-chip is to temperature, humidity and the CO of front end
2Gas concentration is gathered, and the data of gathering are converted to numerary signal, can be undertaken can realizing functions such as remote alarms, remote inquiry, Long-distance Control alternately by gsm wireless network and user.Be example with the remote alarms, after micro-chip compares the alarming value of the signal of front end mobile phone and setting, obtain abnormal signal (namely the signal value of Shou Jiing surpasses warning value), will send signal to the remote interaction unit, starting working after receiving signal in the remote interaction unit, at first judges signal type (temperature, humidity or the CO that receives
2Gas concentration), send out corresponding alarming short message at different signals then.Especially can not regulate automatically at short notice under the situation that returns to steady state in cell cultures microchamber unit, the remote alarms function is just very important, can in time notify the user to pass through artificial the intervention and intervene.
Preferably, described micro-chip processing unit designs based on the MSP430f449 series monolithic.
Preferably, also comprise the steady state information input unit, described steady state input information input unit is used for temperature, humidity and the CO in the input cell cultures microchamber unit
2The steady state value that gas is dense and fluctuation range.
Beneficial effect: the cells in vitro of miniaturization provided by the invention is cultivated measuring and control device, utilizes feedback control, can realize the continuous detecting of cellular activity in the culturing process; Adopt printing opacity acrylic material processing cell cultures microchamber unit, can realize that miniaturization vitro culture vessel make, concrete shape can customize according to demand, and is easy to process and sterilization is simple; Realize the informationization of culture apparatus, in culturing process, to the monitoring of environment, when keeping ambient stable, improve the trackability of experimental data; Can realize remote interaction, the function such as warning, remote inquiry, Long-distance Control of abnomal condition is provided.
Description of drawings
Fig. 1 is structural representation of the present invention;
Fig. 2 is the Temperature Humidity Sensor workflow diagram;
Fig. 3 is the data transmission flow process figure between Temperature Humidity Sensor and the micro-chip processing unit;
Fig. 4 is CO
2The working sensor schema;
Fig. 5 is that the micro-chip processing unit is to the schema of upper computer transmission data;
The schema that Fig. 6 handles, stores and show the data that receive for the micro-chip processing unit;
Fig. 7 is the button control flow chart of steady state information input unit;
Fig. 8 is the work synoptic diagram of remote interaction unit;
Fig. 9 is the workflow diagram of remote alarms.
Embodiment
Below in conjunction with accompanying drawing the present invention is done further explanation.
The cells in vitro that is illustrated in figure 1 as a kind of miniaturization is cultivated measuring and control device, and comprise cell cultures microchamber unit, environmental parameter collecting unit, micro-chip processing unit, feedback regulation unit and remote interaction unit: described cell cultures microchamber unit provides the space for the placement of cell culture container; Described environmental parameter collecting unit is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration detects and detection information is sent to the micro-chip processing unit; Described micro-chip processing unit is handled, is stored and show the information that receives, and produces the feedback regulation signal and sends to the feedback regulation unit; The information that described feedback regulation unit basis receives is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration is regulated; Described micro-chip processing unit carries out information interaction by remote interaction unit and remote service end.
Specified with regard to each component units below.
Cell cultures microchamber unit
Cell cultures microchamber unit provides the space for placing cell culture container, need to combine with heating, humidification device to keep the stable of envrionment temperature and humidity simultaneously, in this case, described cell cultures microchamber unit comprises box body and top cover, described box body is printing opacity acrylic material, described top cover is the heating glass material, and the inside of described box body is provided with a circle tank, and the sidewall of described box body is provided with CO
2Ventilating pit; Be provided with the silica gel hot-plate in the described box body.
Described box body can customize according to the real needs that detect, reaching the purpose with other monitoring device couplings, convenient for production and cultivate before pre-treatment such as sterilization all comparatively simple.The design of tank mainly contains two functions: the one, for humidification provides the water source, under the situation of heat supply, guarantee the high humidity in the box body; The 2nd, play insulation effect, because that specific heat of water holds is bigger, the ability of storing heat is more intense, water filling helps to reduce the temperature degree of disturbing in the box body in tank.Top cover adopts heating glass processing, also can keep transparence preferably when heating function is provided, is convenient to observe.CO
2The design of ventilating pit is the CO that regulates for convenience in the box body
2Gas concentration.The top cover of tank, heating glass, silica gel hot-plate and CO
2Ventilating pit has constituted the major portion of feedback regulation unit jointly, to guarantee the ambient stable in the box body.
The environmental parameter collecting unit
The environmental parameter collecting unit need be to temperature, humidity and the CO in the cell cultures microchamber unit
2Concentration detects, and the environmental parameter collecting unit in this case comprises Temperature Humidity Sensor and CO
2Sensor.Wherein, described Temperature Humidity Sensor is the DHT22 Temperature Humidity Sensor.
The DHT22 Temperature Humidity Sensor can detect relative humidity and temperature simultaneously, signal is calibration and digitizing output all, good (temperature ± 0.1 ℃ of precision, humidity ± 0.1%RH), meet user demand, in this case the working process of Temperature Humidity Sensor and and the micro-chip processing unit between data transmission procedure such as Fig. 2, shown in Figure 3.
Described CO
2Sensor is the infrared non-spectral CO of SRH-5
2Sensor, the infrared non-spectral CO of SRH-5
2Therefore signal of sensor is simulating signal, need carry out A/D and be converted to numerary signal and can store and handle; CO in this case
2The workflow of sensor as shown in Figure 4.
The micro-chip processing unit
Consider that the cell in vitro culture environment can influence cell in external production process, therefore, after the environmental parameter of finishing inside, cell cultures microchamber unit is gathered, need store, handle and show these data, help the user that the change procedure of integrated environment in system's operational process is comprehensively understood, help experimental result is analyzed.
In this case, described micro-chip processing unit is based on the MSP430f449 chip design, and the transmission of degree signal, parameter storage and parameter showed three parts in real time before the micro-chip processing unit mainly comprised.
Can be to temperature, humidity and CO by LED display
2Concentration shows, because the data that micro-chip obtains are the value of integer (inaccurate), therefore need carry out the algorithm correction to the data that micro-chip obtains; In addition, because the storage unit in the micro-chip is less, and readjustment historical data difficulty, so the data transmission after can utilizing serial ports with front-end collection is stored to upper computer; In order to raise the efficiency, reduce the number of times of data transmission, when micro-chip carries out data transmission to upper computer, at first need the pre-treatment of encoding, with temperature, humidity and CO
2Three groups of data integration of concentration are that one group of data transfers to upper computer again; The specific implementation flow process as shown in Figure 5.
Decoding, storage and the display operation that adopts upper computer to carry out data can reduce the burden of micro-chip and the affinity that personnel use.Carry out software programming by MFC and can easily realize correlation function, the function that generally needs upper computer to realize by software comprises: 1, obtain the data that micro-chip transmits and decode, 2, the data and the chart that dynamically show transmission, 3, carry out the selection of serial ports attribute, 4, the storage of data; The specific implementation schema is shown in 6.For data and chart, data are used for the real-time numerical value of display environment parameter, and chart is X-coordinate with time, draw the time dependent performance graph of each environmental parameter.
The feedback regulation unit
As previously mentioned, the top cover of tank, heating glass, silica gel hot-plate and CO
2Ventilating pit has constituted the major portion of feedback regulation unit jointly, to guarantee the ambient stable in the box body.Realize heating function jointly by silica gel heat block and heating glass top cover; The size of its heating power can realize by the resistance of regulating voltage and heater element; By certain algorithm heating power and heat-up time are controlled, just can be realized the temperature in the box body.
According to actual needs, the feedback regulation unit need rely on the steady state information input unit to carry out work, and described steady state input information input unit is used for temperature, humidity and the CO in the input cell cultures microchamber unit
2The steady state value that gas is dense and fluctuation range.Steady state information input unit in this example is equally based on the MSP430f449 chip design, and is designed to press-key structure, and its workflow as shown in Figure 7.
The remote interaction unit
The remote interaction unit is TC35 series double frequency 900/1800MHZ integrated GSM module, and this gsm module carries the RS232 communication interface, can carry out on-line communication with PC or micro-chip easily.Micro-chip is to temperature, humidity and the CO of front end
2Gas concentration is gathered, and the data of gathering are converted to numerary signal, can be undertaken can realizing functions such as remote alarms, remote inquiry, Long-distance Control alternately by gsm wireless network and user.Its principle of work as shown in Figure 8.
Be example with the remote alarms, after micro-chip compares the alarming value of the signal of front end mobile phone and setting, obtain abnormal signal (namely the signal value of Shou Jiing surpasses warning value), will send signal to the remote interaction unit, starting working after receiving signal in the remote interaction unit, at first judges signal type (temperature, humidity or the CO that receives
2Gas concentration), send out corresponding alarming short message at different signals then.Realization flow as shown in Figure 9.
The above only is preferred implementation of the present invention; be noted that for those skilled in the art; under the prerequisite that does not break away from the principle of the invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (9)
1. the cells in vitro of a miniaturization is cultivated measuring and control device, it is characterized in that: comprise cell cultures microchamber unit, environmental parameter collecting unit, micro-chip processing unit and feedback regulation unit:
Described cell cultures microchamber unit provides the space for the placement of cell culture container;
Described environmental parameter collecting unit is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration detects and detection information is sent to the micro-chip processing unit;
Described micro-chip processing unit is handled, is stored and show the information that receives, and produces the feedback regulation signal and sends to the feedback regulation unit;
The information that described feedback regulation unit basis receives is to temperature, humidity and CO in the cell cultures microchamber unit
2Gas concentration is regulated.
2. the cells in vitro of miniaturization according to claim 1 is cultivated measuring and control device, it is characterized in that: described cell cultures microchamber unit comprises box body and top cover, described box body is printing opacity acrylic material, described top cover is the heating glass material, the inside of described box body is provided with a circle tank, and the sidewall of described box body is provided with CO
2Ventilating pit.
3. the cells in vitro of miniaturization according to claim 2 is cultivated measuring and control device, it is characterized in that: be provided with the silica gel hot-plate in the described box body.
4. the cells in vitro of miniaturization according to claim 1 is cultivated measuring and control device, and it is characterized in that: described environmental parameter collecting unit comprises Temperature Humidity Sensor and CO
2Sensor.
5. the cells in vitro of miniaturization according to claim 4 is cultivated measuring and control device, and it is characterized in that: described Temperature Humidity Sensor is the DHT22 Temperature Humidity Sensor, described CO
2Sensor is the infrared non-spectral CO of SRH-5
2Sensor.
6. the cells in vitro of miniaturization according to claim 1 is cultivated measuring and control device, and it is characterized in that: also comprise the remote interaction unit, described micro-chip processing unit carries out information interaction by remote interaction unit and remote service end.
7. the cells in vitro of miniaturization according to claim 6 is cultivated measuring and control device, it is characterized in that: described remote interaction unit is TC35 series double frequency 900/1800MHZ integrated GSM module.
8. the cells in vitro of miniaturization according to claim 1 is cultivated measuring and control device, and it is characterized in that: described micro-chip processing unit designs based on the MSP430f449 series monolithic.
9. the cells in vitro of miniaturization according to claim 1 is cultivated measuring and control device, it is characterized in that: also comprise the steady state information input unit, described steady state input information input unit is used for temperature, humidity and the CO in the input cell cultures microchamber unit
2The steady state value that gas is dense and fluctuation range.
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CN107164222A (en) * | 2017-06-22 | 2017-09-15 | 成都远洋蓝猫科技有限公司 | Sample process box for Bacteria Detection |
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CN110438002A (en) * | 2019-08-06 | 2019-11-12 | 东南大学 | The wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell |
CN113789263A (en) * | 2021-08-30 | 2021-12-14 | 东南大学 | Multi-channel system for in-vitro neural cell network multi-parameter real-time monitoring |
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CN106434343A (en) * | 2016-09-29 | 2017-02-22 | 黑龙江天晴干细胞股份有限公司 | Remote biological cell culture apparatus, auxiliary system and application of system |
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CN113789263A (en) * | 2021-08-30 | 2021-12-14 | 东南大学 | Multi-channel system for in-vitro neural cell network multi-parameter real-time monitoring |
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Application publication date: 20130918 |