CN110438002A - The wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell - Google Patents

The wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell Download PDF

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Publication number
CN110438002A
CN110438002A CN201910722269.3A CN201910722269A CN110438002A CN 110438002 A CN110438002 A CN 110438002A CN 201910722269 A CN201910722269 A CN 201910722269A CN 110438002 A CN110438002 A CN 110438002A
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cell
thermal resistance
resistance sensor
film platinum
temperature monitoring
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CN201910722269.3A
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CN110438002B (en
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杨芳
丁佳序
顾宁
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Southeast University
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Southeast University
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/12Well or multiwell plates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/06Plates; Walls; Drawers; Multilayer plates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48Automatic or computerized control

Abstract

The present invention relates to a kind of wireless multi-channel systems of temperature monitoring during adherent growth for cell, including constant incubator, film platinum thermal resistance sensor, tissue culture plate, 3D printing framework and resistor detecting device, the tissue culture plate is placed in constant incubator, the tissue culture plate is equipped with culture hole, film platinum thermal resistance sensor and 3D printing framework are equipped in the culture hole, the film platinum thermal resistance sensor is connected by 3D printing framework with tissue culture plate;The film platinum thermal resistance sensor is connected with resistor detecting device;The invention discloses a kind of wireless multi-channel systems of temperature monitoring during adherent growth for cell, in film platinum thermal resistance sensor surface seeding cell, while cell culture, wireless monitor cell temperature situation of change, not by the interference of intermediate medium, good biocompatibility, it is noninvasive to cell.

Description

The wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell
Technical field
The present invention relates to a kind of wireless multi-channel systems of temperature monitoring during adherent growth for cell, belong to cell Temperature monitoring system field.
Background technique
Temperature is the most important and most basic physiological parameter of cellular activity, and each physiology course of cell is along with temperature Variation, some researches show that with the differentiation of human pluripotent stem cell, main metabolic mode is also gradually from glycolysis to oxidation Phosphorylation transformation, this transformation are also reacted in cell temperature variation level.Some researches show that ambient temperature is to regulating cell simultaneously Activity also has remarkable result, and to different cells, regulating effect is different, such as thermostimulation can promote osteoblast increasing Differentiation is grown, while thermostimulation can also reduce the proliferation activity of Testis Sertoli Cells in Rat, therefore the temperature in cell growth process Detection, is of great significance to the research of life science.
Mainly have for the technology that cell temperature measures at present: fluorescence nano thermometer, scanning thermal probe, micro-nano heat Thermocouple probe.
Fluorescence nano thermometer utilizes quantum dot fluorescence labeling probe, temperature sensitive fluorescent nano particle, green fluorescent protein etc. Living cells is marked in material, by the variation of the characteristics such as the wavelength of fluorescence signal, intensity, service life, reacts living cells temperature Variation.Fluorescence nano thermometer spatial resolution with higher and temperature change sensitivity, but be difficult to accomplish real-time monitoring, And there is also deficiencies in terms of repeatability and biocompatibility.
Scan thermal probe, in STM(scanning tunneling microscope) scanning probe top, develop one based on pyroelectric effect Temperature sensor can carry out body surface temperature imaging in nanometer scale, want to appointed condition and operator's technology It asks higher, and is not suitable as temperature real time monitoring means.
Micro-nano thermocouple probe is based on metal Seebeck effect, temperature signal is converted into thermo-electromotive force signal, is suitable for Unicellular interior temperature change is detected, needs to puncture when having the advantages that measurement accuracy is high, measurement temperature range is wide, but using thin Born of the same parents belong to invasive detection, can only measure the temperature change of individual cells, and the thermometric time is shorter.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, provides a kind of for temperature prison during cell adherent growth The wireless multi-channel system of survey, to solve problems of the prior art.
To achieve the above object, The technical solution adopted by the invention is as follows:
The wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell, including constant incubator, film platinum Thermal resistance sensor, tissue culture plate, 3D printing framework and resistor detecting device, the tissue culture plate are placed on constant temperature training It supports in case, the tissue culture plate is equipped with culture hole, is equipped with film platinum thermal resistance sensor in the culture hole and 3D is beaten Framework is printed, the film platinum thermal resistance sensor is connected by 3D printing framework with tissue culture plate;The film platinum resistance thermometer sensor, Sensor is connected with resistor detecting device.
As an improvement of the present invention, the tissue culture plate is equipped with corresponding with film platinum thermal resistance sensor Through-hole;Groove corresponding with film platinum thermal resistance sensor is equipped in the 3D printing framework.
As an improvement of the present invention, the quantity of the film platinum thermal resistance sensor is at least 12, the culture The quantity in hole is at least 12.
It as an improvement of the present invention, further include computer, the computer is examined by wireless network terminal and resistance Device is surveyed to be connected.Host computer monitoring system is loaded in computer, by calibration curve parameter, temperature monitoring interface, temperature monitoring Three interface compositions of history.Host computer monitors system and receives resistor detecting device data, after treatment, every group of biography of real-time display The collected temperature information of sensor, and carry out data record and the drafting of temperature monitoring history.
As an improvement of the present invention, the wireless network terminal is bluetooth.
It as an improvement of the present invention, further include lithium battery, the lithium battery is arranged in constant incubator, the lithium Battery is connected with resistor detecting device.
As an improvement of the present invention, the 3D printing framework be white photosensitive resin material by Stereo Lithography at The printing of type technique.
As an improvement of the present invention, during a kind of adherent growth for cell temperature monitoring it is wireless more Application of the channel in the cell of measurement.
As an improvement of the present invention, the cell includes that tumour cell, stem cell, endothelial cell and nerve are thin Born of the same parents.
As an improvement of the present invention, the measuring method of the cell, includes the following steps:
Step 1: coating processing is carried out to film platinum thermal resistance sensor using biomaterial, is dried overnight in super-clean bench;
Step 2: being fixed film platinum thermal resistance sensor, 3D printing framework, tissue culture plate using silicone heat-conducting glue, building Cell culture environment;
Step 3: broad-spectrum sterilization is carried out to equipment using ethylene oxide gas at normal temperature;
Step 4: being 5 × 10 by concentration8The cell solution of/L is inoculated into 3D printing framework, and training is added in tissue culture plate Nutrient solution is put into constant incubator and cultivates;
Step 5: computer is opened by bluetooth data transmission and observes its temperature variations in real time.
Film platinum thermal resistance sensor utilizes temperature change during platinum resistance thermometer sensor, competent cell adherent growth;3D printing frame Body, for fixing platinum thermal resistance sensor, inner space provides cell culture environment;Resistor detecting device, for measuring multiple groups The resistance value and data of film platinum thermal resistance sensor are transmitted;Computer, be used for data receiver, processing, preservation, and real-time display its Temperature change.The film platinum thermal resistance sensor can induce the growth of cell attachment sensor surface.
The resistance detecting circuit has multiple sense channels, and uses Kelvin's four-wire system resistance detecting circuit.It is described Resistance detecting circuit uses 7.4V lithium battery power supply, and is carried out data transmission by bluetooth module, realizes wireless portable.The meter Calculation machine receives data by bluetooth, to data conversion, analysis, saves, and in its temperature variations of host computer real-time display.
Due to using the above technology, the present invention compared with the prior art, is had the advantage that as follows:
The invention discloses a kind of wireless multi-channel systems of temperature monitoring during adherent growth for cell, in film platinum heat Electric resistance sensor surface seeding cell, while cell culture, wireless monitor cell temperature situation of change, not by intermediate medium Interference, good biocompatibility is noninvasive to cell;Multiple experimental groups and multiple right can be set simultaneously on one piece of tissue culture plate According to group, favorable repeatability.Measuring device uses lithium battery power supply, it can be achieved that 24 hours or more wireless temperature monitorings, by upper Position machine data processing system can observe temperature variations in real time, and experimenter is facilitated to observe.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of tissue culture plate;
Fig. 2 is a kind of schematic diagram of the wireless multi-channel system of temperature monitoring during the adherent growth for cell;
Fig. 3 is neural stem cell temperature and control group temperature (environment temperature) variation in 24 hours;
Fig. 4 is during induced nerve stem cells are adherent, and experimental group and control group temperature difference change;
In figure: 1, computer, 2, constant incubator, 3, lithium battery, 4, bluetooth, 5, resistor detecting device, 6, tissue culture plate, 7, 3D printing framework, 8, film platinum thermal resistance sensor, 9, groove, 10, through-hole, 11, culture hole.
Specific embodiment
With reference to the accompanying drawings and detailed description, the present invention is furture elucidated.
In conjunction with attached drawing as it can be seen that during a kind of adherent growth for cell temperature monitoring wireless multi-channel system, including Constant incubator 2, film platinum thermal resistance sensor 8, tissue culture plate 6,3D printing framework 7 and resistor detecting device 5, it is described Tissue culture plate 6 is placed in constant incubator 2, and the tissue culture plate 6 is equipped with culture hole 11, is set in the culture hole 11 Have film platinum thermal resistance sensor 8 and a 3D printing framework 7, the film platinum thermal resistance sensor 8 by 3D printing framework 7 with Tissue culture plate 6 is connected;The film platinum thermal resistance sensor 8 is connected with resistor detecting device 5.
The tissue culture plate 6 is equipped with through-hole 10 corresponding with film platinum thermal resistance sensor 8;The 3D printing frame Groove 9 corresponding with film platinum thermal resistance sensor 8 is equipped in body 7.
The quantity of the film platinum thermal resistance sensor 8 is at least 12, and the quantity of the culture hole 11 is at least 12.
It further include computer 1, the computer 1 is connected by wireless network terminal with resistor detecting device 5.It is described wireless The network terminal is bluetooth 4.
It further include lithium battery 3, the lithium battery 3 is arranged in constant incubator 2, and the lithium battery 3 is filled with resistance detection 5 are set to be connected.
The 3D printing framework 7 is that white photosensitive resin material is printed by stereolithography apparatus technique.
Wireless multi-channel system, uses neural stem cell as monitoring object described in present embodiment, as shown in Figure 1, 3D printing framework 7 is made using the design of AutoCAD graphics software, stereolithography apparatus (SLA) technique, is led using nontoxic silicone Hot glue, by Collagen type-I coating, treated that film platinum thermal resistance sensor 8(improves its biocompatibility) and 3D printing framework 7 It is fixed in six porocyte culture plates 6, draws 8 conducting wire of film platinum thermal resistance sensor, at normal temperature using ethylene oxide to setting Standby to sterilize, this step is intended to construct cell growth and temperature sensing environment.
Next, inoculum density is 5 × 10 in super-clean bench8The neural stem cell of/L is inoculated into film platinum resistance thermometer sensor, sensing Film platinum thermal resistance sensor 8 connect with resistor detecting device 5, is put into constant incubator 2 by 8 surface of device, opens computer 1, data are transmitted by bluetooth 4, observe its temperature variations in real time, overall system effect is as shown in Figure 2.
Six experimental groups (neural stem cell+culture medium) and six control groups (culture medium) are arranged in this embodiment, for letter Clean explanation, one group chosen in computer 1 are shown, and the group temperature of Fig. 3 display inoculation neural stem cell is higher than pair gradually According to group, temperature gap is gradually stable at 0.4 DEG C or so.Fig. 4 show the cell of experimental group during adherent with control group Temperature gap variation, gradually rises in 1 hour.
Present embodiment effectively can carry out real time temperature monitoring by the cell to thousands of orders of magnitude, while have volume Small, fast response time, steady performance.
Above-described embodiment is only the preferred technical solution of the present invention, and is not construed as limitation of the invention, the present invention Protection scope should with claim record technical solution, including claim record technical solution in technical characteristic etc. It is protection scope with alternative, i.e., equivalent replacement within this range is improved, also within protection scope of the present invention.

Claims (10)

1. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell, it is characterised in that: including constant temperature Incubator, film platinum thermal resistance sensor, tissue culture plate, 3D printing framework and resistor detecting device, the cell culture Plate is placed in constant incubator, and the tissue culture plate is equipped with culture hole, is equipped with film platinum resistance thermometer sensor, in the culture hole Sensor and 3D printing framework, the film platinum thermal resistance sensor are connected by 3D printing framework with tissue culture plate;Institute Film platinum thermal resistance sensor is stated to be connected with resistor detecting device.
2. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 1, It is characterized by: the tissue culture plate is equipped with through-hole corresponding with film platinum thermal resistance sensor;The 3D printing frame It is equipped with groove corresponding with film platinum thermal resistance sensor in vivo.
3. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 1, It is characterized by: the quantity of the film platinum thermal resistance sensor is at least 12, the quantity of the culture hole is at least 12.
4. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 1, It is characterized by also including computer, the computer is connected by wireless network terminal with resistor detecting device.
5. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 4, It is characterized by: the wireless network terminal is bluetooth.
6. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 1, It is characterized by also including lithium battery, the lithium battery is arranged in constant incubator, the lithium battery and resistor detecting device It is connected.
7. the wireless multi-channel system of temperature monitoring during a kind of adherent growth for cell according to claim 1, It is characterized by: the 3D printing framework is that white photosensitive resin material is printed by stereolithography apparatus technique.
8. the wireless multi-channel of temperature monitoring is being surveyed during a kind of adherent growth for cell described in -7 according to claim 1 Application in fixed cell.
9. application according to claim 8, it is characterised in that: the cell includes tumour cell, stem cell, endothelial cell And nerve cell.
10. application according to claim 8, which is characterized in that the measuring method of the cell includes the following steps:
Step 1: coating processing is carried out to film platinum thermal resistance sensor using biomaterial, is dried overnight in super-clean bench;
Step 2: being fixed film platinum thermal resistance sensor, 3D printing framework, tissue culture plate using silicone heat-conducting glue, building Cell culture environment;
Step 3: broad-spectrum sterilization is carried out to equipment using ethylene oxide gas at normal temperature;
Step 4: being 5 × 10 by concentration8The cell solution of/L is inoculated into 3D printing framework, and training is added in tissue culture plate Nutrient solution is put into constant incubator and cultivates;
Step 5: computer is opened by bluetooth data transmission and observes its temperature variations in real time.
CN201910722269.3A 2019-08-06 2019-08-06 Wireless multichannel system for monitoring temperature in cell adherent growth process Active CN110438002B (en)

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CN110982682A (en) * 2019-11-20 2020-04-10 东南大学 High-throughput cell detection system based on passive wireless technology
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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Cited By (3)

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Publication number Priority date Publication date Assignee Title
CN110982682A (en) * 2019-11-20 2020-04-10 东南大学 High-throughput cell detection system based on passive wireless technology
CN110982682B (en) * 2019-11-20 2022-07-29 东南大学 High-throughput cell detection system based on passive wireless technology
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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