CN111949055B - Independent temperature control system and method for microfluidic culture chip - Google Patents
Independent temperature control system and method for microfluidic culture chip Download PDFInfo
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- CN111949055B CN111949055B CN202010765405.XA CN202010765405A CN111949055B CN 111949055 B CN111949055 B CN 111949055B CN 202010765405 A CN202010765405 A CN 202010765405A CN 111949055 B CN111949055 B CN 111949055B
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- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/19—Control of temperature characterised by the use of electric means
- G05D23/20—Control of temperature characterised by the use of electric means with sensing elements having variation of electric or magnetic properties with change of temperature
- G05D23/22—Control of temperature characterised by the use of electric means with sensing elements having variation of electric or magnetic properties with change of temperature the sensing element being a thermocouple
Abstract
The invention relates to an independent temperature control system of a microfluidic culture chip and a temperature control method thereof, wherein the independent temperature control system of the microfluidic culture chip comprises at least one refrigerating device, at least one temperature sensing probe and at least one temperature controller, the temperature sensing probe detects the temperature of experimental seawater of the microfluidic culture chip in real time and sends a feedback signal to the temperature controller in the real-time flowing process of the experimental seawater of the microfluidic culture chip, and the temperature controller controls the refrigerating device to refrigerate the real-time dynamically updated experimental seawater based on the feedback signal sent by the temperature sensing probe, so that the temperature of the experimental seawater flowing into the microfluidic culture chip can be always kept in a set temperature range.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to an independent temperature control system of a microfluidic culture chip and a temperature control method thereof.
Background
Microfluidic culture chips refer to chemical or biological laboratories built on a centimeter square chip. The basic operation can be integrated on a very small chip, and the micro-channel forms a network to control a fluid penetration system, thereby realizing the functions of chemical synthesis, biological detection and the like. However, temperature control is often required in chemical synthesis and biological detection processes, for example, in a gene sequencing PCR detection process, cyclic heat preservation operation is required at temperatures of 95 ℃, 65 ℃, 4 ℃ and the like, the culture of marine organisms such as jellyfish, seaweed and the like generally needs to be maintained at 8-15 ℃, and in most cases, the microfluidic culture chip has the requirement of multi-unit independent temperature control, that is, the temperature requirements in the microfluidic culture chip are different based on different requirements of growth conditions of different microorganisms.
The traditional temperature control modes for the microfluidic culture chip mainly comprise two modes, wherein one mode is a commercial temperature table, and specifically, the whole microfluidic chip is placed on the commercial temperature table to directly heat or refrigerate the microfluidic chip. The other temperature control mode is to place the whole microfluidic culture chip into a box body which can be controlled to have large enough temperature, the temperature control range is large, and the development is mature. However, the two conventional temperature control methods have disadvantages. Adopt commercial temperature platform to carry out the mode of accuse temperature, its holistic intensification process of easy quick control, nevertheless because commercial temperature platform does not have heat abstractor, need wait for longer time at its cooling in-process, still probably because the heat can not go out and lead to the control cabinet to be damaged. However, the whole microfluidic culture chip is put into a large enough temperature-controllable box, which is simple and easy to implement, but makes it difficult to observe the internal conditions of the microfluidic culture chip, that is, the path of the microscope for observing the interior of the microfluidic culture chip is affected. Although a large volume of water can be refrigerated for later use and input into the microfluidic culture chip to control the temperature of the chamber of the microfluidic culture chip, the energy loss at room temperature is large, and the temperature is not stably and accurately controlled by a cold water temperature control mode. In addition, for the multi-unit microfluidic culture chip, in order to realize independent temperature control of each microfluidic culture chip, a commercial temperature table or a large thermostat needs to be independently arranged for each microfluidic culture chip, which inevitably results in high control cost and occupies more experimental positions, so that the traditional temperature control mode is difficult to realize independent temperature control of the multi-unit microfluidic culture chip, in other words, the traditional temperature control mode is difficult to meet the independent temperature control requirement of the multi-unit microfluidic culture chip.
Generally speaking, the traditional temperature control mode can not realize the accurate temperature control of the microfluidic culture chip, but also influences the observation of microorganisms cultured in the microfluidic culture chip, and simultaneously is difficult to meet the independent temperature control requirement of the multi-unit microfluidic culture chip.
Disclosure of Invention
Based on this, an object of the present invention is to provide an independent temperature control system of a microfluidic culture chip and a temperature control method thereof, where the independent temperature control system of the microfluidic culture chip has high temperature control precision, can provide an observation path for microscope observation, and is suitable for independent temperature control of a multi-unit microfluidic culture chip.
The invention also aims to provide an independent temperature control system of the microfluidic culture chip and a temperature control method thereof, wherein based on the characteristic of real-time dynamic update of the experimental seawater of the microfluidic culture chip, the experimental seawater flowing into the microfluidic culture chip is always kept at the set temperature by refrigerating the experimental seawater in the flowing process of the experimental seawater, so that the temperature control of the whole chamber of the microfluidic culture chip is realized.
Another objective of the present invention is to provide an independent temperature control system of a microfluidic culture chip and a temperature control method thereof, where the independent temperature control system of the microfluidic culture chip includes at least one temperature controller, at least one refrigeration device, and at least one temperature sensing probe, and the temperature controller controls the operation of the refrigeration device based on the temperature of the microfluidic culture chip detected by the temperature sensing probe in real time, so as to accurately control the temperature of the microfluidic culture chip.
The invention also aims to provide an independent temperature control system of the microfluidic culture chip and a temperature control method thereof, wherein the refrigerating device adopts a semiconductor refrigerating sheet for refrigeration and is provided with a heat dissipation device, the refrigerating effect is good, the reliability is high, and the heat dissipation device is used for dissipating heat so as not to damage the refrigerating structure of the semiconductor refrigerating sheet.
Another object of the present invention is to provide an independent temperature control system for a microfluidic culture chip and a temperature control method thereof, wherein the refrigeration device uses a flat conduit to transport the experimental seawater to the microfluidic culture chip, and the experimental seawater flowing through the flat conduit is refrigerated by the semiconductor refrigeration sheet, which is beneficial to ensuring a large contact area between the semiconductor refrigeration sheet and the flat conduit, thereby ensuring a good refrigeration effect.
Another objective of the present invention is to provide an independent temperature control system of a microfluidic culture chip and a temperature control method thereof, wherein the temperature controller is preset with a temperature range, and based on different temperature ranges set by different temperature controllers, the independent temperature control system of the microfluidic culture chip can meet the temperature requirements of different units of the microfluidic culture chip, that is, the independent temperature control system of the microfluidic culture chip can independently control the temperature of multiple units of the microfluidic culture chip.
The invention also aims to provide an independent temperature control system of the microfluidic culture chip and a temperature control method thereof, wherein the independent temperature control system of the microfluidic culture chip adopts a digital temperature controller to control the temperature of the microfluidic culture chip, has the advantages of high temperature control precision, long service life and low price, can replace mechanical temperature control, and simultaneously has a delayed starting function.
Another object of the present invention is to provide an independent temperature control system of a microfluidic culture chip and a temperature control method thereof, wherein a temperature of experimental seawater in the microfluidic culture chip is detected by using a superfine thermocouple wire, so that a large temperature measurement area is not occupied, and an observation path can be provided for a microscope, thereby facilitating observation of organisms cultured in the microfluidic culture chip.
In order to achieve at least one of the above objects, the present invention provides an independent temperature control system for a microfluidic culture chip, comprising:
at least one refrigerating device, wherein the refrigerating device is used for refrigerating the experiment seawater dynamically updated in real time of the microfluidic culture chip;
the temperature controller is electrically connected with the refrigerating device; and
and two ends of the temperature sensing probe are respectively arranged on the microfluidic culture chip and the temperature controller and are used for detecting the temperature of the experimental seawater in the microfluidic culture chip in real time and sending a feedback signal to the temperature controller, and the temperature controller controls the work of the refrigerating device based on the feedback signal sent by the temperature sensing probe, so that the temperature of the experimental seawater dynamically updated in real time is kept in the temperature range set by the temperature controller.
In an embodiment of the invention, the refrigeration device comprises two semiconductor refrigeration pieces which are electrically connected to the temperature controller and a flat conduit arranged between the two semiconductor refrigeration pieces, the flat conduit is connected to the experimental seawater bottle and the microfluidic culture chip, and the two semiconductor refrigeration pieces refrigerate when being controlled and started by the temperature controller so as to reduce the temperature of the flat conduit, thereby reducing the temperature of the experimental seawater flowing through the flat conduit.
In an embodiment of the present invention, the flat type catheter is made of a metal material with good thermal conductivity.
In an embodiment of the invention, the two semiconductor refrigeration sheets are adhered to the flat conduit through a heat-conducting adhesive.
In an embodiment of the present invention, the semiconductor chilling plate is sized to be greater than or equal to the flat type conduit.
In an embodiment of the present invention, the cooling device further includes two cooling fins and two fans, the cooling fins are disposed on the outer sides of the corresponding semiconductor cooling fins, and the fans are disposed on the outer sides of the corresponding cooling fins.
In an embodiment of the invention, the heat dissipation plate is adhered to the corresponding semiconductor refrigeration plate by a heat conductive adhesive, and the fan is fixed to the corresponding heat dissipation plate by a screw fixing method.
In an embodiment of the present invention, the independent temperature control system of the microfluidic culture chip further includes a power supply, the power supply is electrically connected to the refrigerating device and the temperature controller, when the power supply is started, the temperature-sensing probe detects the temperature of the experimental seawater in the microfluidic culture chip, when the temperature of the experimental seawater in the microfluidic culture chip detected by the temperature-sensing probe exceeds the temperature range, the temperature controller controls the refrigerating device to refrigerate, and when the temperature of the experimental seawater in the microfluidic culture chip detected by the temperature-sensing probe is lower than the temperature range, the temperature controller controls the refrigerating device to stop refrigerating.
In an embodiment of the present invention, the temperature sensing probe is provided as any one of a waterproof head, a water droplet head, a magnetic head, and a thermocouple wire.
In an embodiment of the invention, the temperature controller is provided as a digital temperature controller of type XH-W1315.
In an embodiment of the present invention, the temperature controller includes a display screen, and the display screen is used for observing the temperature of the experimental seawater in the microfluidic culture chip detected by the temperature-sensing probe in real time.
In one embodiment of the invention, the power supply is set to 12V dc power.
In an embodiment of the present invention, the temperature range set by the temperature controller is set as: 8-16 ℃.
In an embodiment of the invention, the independent temperature control system of the microfluidic culture chip includes four refrigeration devices and four temperature controllers, and the four temperature controllers are connected in parallel to the power supply to independently control the temperature of the experimental seawater in the microfluidic culture chip of the four independent units.
In an embodiment of the invention, the temperature ranges set by the four temperature controllers are respectively: 8-10 ℃, 10-12 ℃, 12-14 ℃ and 14-16 ℃.
The invention also provides a temperature control method of the microfluidic culture chip in another aspect, which comprises the following steps:
(a) detecting the temperature of the experimental seawater in the microfluidic culture chip in real time through a temperature-sensitive probe; and
(b) and controlling the work of the refrigerating device by the temperature-sensitive controller based on the feedback of the temperature-sensitive probe to the temperature of the experimental seawater in the microfluidic culture chip.
In an embodiment of the invention, in the step (b), the temperature controller is set with a temperature range, and when the temperature probe detects that the temperature of the experimental seawater in the microfluidic culture chip exceeds the temperature range, the temperature controller controls the refrigerating device to refrigerate.
In an embodiment of the invention, in the step (b), when the temperature of the experimental seawater detected by the temperature-sensitive probe in the microfluidic culture chip is lower than the temperature range, the temperature-sensitive controller controls the refrigeration device to stop refrigerating.
In an embodiment of the present invention, the temperature range is: 8-16 ℃.
Further objects and advantages of the invention will be fully apparent from the ensuing description and drawings.
Drawings
Fig. 1 is a schematic block diagram of the temperature control process of the independent temperature control system of the microfluidic culture chip according to a preferred embodiment of the invention.
FIG. 2 is a schematic view of the special shape processing of the flat conduit of the independent temperature control system of the microfluidic culture chip according to the above preferred embodiment of the present invention.
Fig. 3A is a front view of the refrigeration device of the independent temperature control system of the microfluidic culture chip according to the above preferred embodiment of the invention.
Fig. 3B is a top view of the refrigeration device of the independent temperature control system of the microfluidic culture chip according to the above preferred embodiment of the present invention.
Fig. 4 is a schematic structural diagram of the temperature controller of the independent temperature control system of the microfluidic culture chip according to the above preferred embodiment of the invention.
Fig. 5A is a front view of the microfluidic culture chip according to the above preferred embodiment of the present invention.
Fig. 5B is a top view of the microfluidic culture chip according to the above preferred embodiment of the present invention.
The meaning of the reference symbols in the drawings is:
10-a refrigeration device; 11-semiconductor refrigerating sheet; 12-a flat catheter; 13-a heat sink; 14-a fan; 15-heat conducting glue; 20-temperature sensing probe; 30-a temperature controller; 31-a display screen; 40-a power supply; 50-microfluidic culture chip; 51-feeding port of micro-fluidic culture chip; 52-Experimental seawater inlet and outlet of microfluidic culture chip.
Detailed Description
To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The independent temperature control system can control the temperature of the microfluidic culture chip chamber to be between 1 and 20 ℃, and preferably between 8 and 16 ℃. The micro-fluidic culture chip has the characteristics of small volume and real-time dynamic updating of experimental seawater, namely the experimental seawater in the inlet and outlet guide pipes of the micro-fluidic culture chip is in a real-time flowing state. By utilizing the characteristic that the microfluidic culture chip dynamically updates the experimental seawater in real time, the invention adopts a method of refrigerating and cooling a guide pipe through which the experimental seawater flows by a semiconductor refrigerating sheet in the flowing process of the experimental seawater, so that the experimental seawater flowing into the chamber of the microfluidic culture chip is always kept at the set temperature, thereby realizing the temperature control of the whole chamber of the microfluidic culture chip.
As shown in fig. 1 to 5B, an independent temperature control system of a microfluidic culture chip according to a preferred embodiment of the present invention is specifically illustrated.
As shown in fig. 1 to 4, the independent temperature control system of the microfluidic culture chip includes at least one refrigeration device 10, at least one temperature-sensing probe 20, and at least one temperature controller 30 electrically connected to the refrigeration device 10, where the refrigeration device 10 is configured to refrigerate the experimental seawater dynamically updated in real time by the microfluidic culture chip 50; the two ends of the temperature-sensing probe 20 are respectively arranged on the microfluidic culture chip 50 and the temperature controller 30, so as to detect the temperature of the experimental seawater in the microfluidic culture chip 50 in real time and send a feedback signal to the temperature controller 30, and the temperature controller 30 controls the operation of the refrigerating apparatus 10 based on the feedback signal sent by the temperature-sensing probe 20, so that the temperature of the experimental seawater dynamically updated in real time is maintained within the temperature range set by the temperature controller 30.
Specifically, the independent temperature control system of the microfluidic culture chip further comprises a power supply 40, and the power supply 40 is electrically connected to the refrigerating device 10 and the temperature controller 30 to provide electric energy output for the refrigerating device 10 and the temperature controller 30; when the power supply 40 is started, the temperature-sensing probe 20 detects the temperature of the experimental seawater in the microfluidic culture chip 50 in real time, when the temperature-sensing probe 20 detects that the temperature of the experimental seawater in the microfluidic culture chip 50 exceeds the temperature range, the temperature controller 30 controls the refrigerating device 10 to refrigerate, and when the temperature-sensing probe 20 detects that the temperature of the experimental seawater in the microfluidic culture chip 50 is lower than the temperature range, the temperature controller 30 controls the refrigerating device 10 to stop refrigerating, so that the temperature of the experimental seawater is always kept in the temperature range, and thus the accurate control of the temperature in the chamber of the microfluidic culture chip 50 is realized.
Further, the refrigeration device 10 includes two semiconductor refrigeration sheets 11 electrically connected to the temperature controller 30 and a flat conduit 12 disposed between the two semiconductor refrigeration sheets 11, the flat conduit 12 is connected to the experimental seawater bottle and the microfluidic culture chip 50, and the two semiconductor refrigeration sheets 11 perform refrigeration when being controlled and started by the temperature controller 30 to reduce the temperature of the flat conduit 12, so as to reduce the temperature of the experimental seawater flowing through the flat conduit 12, thereby controlling the temperature of the experimental seawater input to the chamber of the microfluidic culture chip 50 to be kept within the temperature range.
It is worth mentioning that the flow process and the refrigeration process of the experimental seawater of the whole independent temperature control system are as follows: the experimental seawater in the experimental seawater bottle flows into the flat conduit 12 under the control of the micro-fluidic pump, the temperature controller 30 controls the semiconductor refrigerating sheet 11 to refrigerate based on the feedback of the temperature sensing probe 20, so that the temperature of the experimental seawater in the flat conduit 12 is reduced, the experimental seawater with the temperature within the temperature range is conveyed into the cavity of the micro-fluidic culture chip 50 through the flat conduit 12, and then flows out of the waste liquid bottle through the outflow conduit of the micro-fluidic culture chip 50. The temperature-sensing probe 20 detects the temperature of the experimental seawater of the microfluidic culture chip 50 in real time, and the temperature controller 30 controls and adjusts the temperature of the experimental seawater flowing into the microfluidic culture chip 50 based on the real-time feedback of the temperature-sensing probe 20, so as to ensure that the temperature of the chamber of the microfluidic culture chip 50 can be kept within the set temperature range. Therefore, it can be understood that the temperature of the experimental seawater is controlled in the flowing process of the experimental seawater, so that the temperature of the microfluidic culture chip 50 is controlled, and the temperature control is accurate, reliable and stable.
It can also be understood that, in the present invention, by cooling the flat conduit 12, the temperature of the experimental seawater flowing into the chamber of the microfluidic culture chip 50 can be always kept within the temperature range preset by the temperature controller 30, so as to achieve precise control of the temperature of the entire chamber of the microfluidic culture chip 50.
Specifically, the working principle of the semiconductor chilling plate 11 is as follows: by using the Peltier effect of the semiconductor materials, when direct current passes through a galvanic couple formed by connecting two different semiconductor materials in series, heat can be absorbed and released at two ends of the galvanic couple respectively, and the aim of refrigeration can be fulfilled. The refrigerating technology which generates negative thermal resistance is characterized by no moving parts and higher reliability. In order to achieve a good cooling effect, the contact area between the semiconductor cooling plate 11 and the flat conduit 12 needs to be increased, so that the circular conduit at the location to be cooled is changed into a flat shape, and a metal material with good thermal conductivity (such as aluminum, etc.) is used to form the flat conduit 12, and the size of the flat conduit 12 should be smaller than or equal to the size of the semiconductor cooling plate 11, but should not be too small, i.e. the size of the flat conduit 12 should preferably be smaller than or equal to the size of the semiconductor cooling plate 11 to ensure a large contact area between the flat conduit 12 and the semiconductor cooling plate 11, thereby ensuring a good cooling effect. The flow tendency of experimental seawater through the flattened conduit 12 is shown in fig. 2.
Preferably, in this embodiment of the present invention, the thickness of the flat type conduit 12 is 2mm to 4mm, the flat type conduit 12 has a special shape, and thus may need to be custom-manufactured, wherein when the flat type conduit 12 is applied, the flat type conduit 12 may be connected with a conventional conduit through a conduit connector at the inlet and outlet of the flat type conduit 12, so it can be understood that the flat type conduit 12 may be connected with the experimental sea water bottle and the microfluidic culture chip 50 through a conduit of a common shape (e.g., a round conduit), and the present invention is not limited thereto.
In particular, in the preferred embodiment of the present invention, in order to ensure the heat transfer effect, two semiconductor cooling fins 11 are adhered to the flat type conduit 12 by a heat conducting glue 15, and the cooling fins, the heat radiating fins and the flat type conduit may be additionally fixed by screws.
In addition, it is worth mentioning that in order to ensure that the semiconductor refrigeration piece 11 can work normally, a heat dissipation device or assembly needs to be installed outside the semiconductor refrigeration piece 11, so that heat can be dissipated to the outside in time in the refrigeration process, otherwise, the refrigeration structure of the semiconductor refrigeration piece 11 can be damaged. Therefore, in the preferred embodiment of the present invention, the cooling device 10 further includes two cooling fins 13 and two fans 14, the cooling fins 13 are disposed on the outer sides of the corresponding semiconductor cooling fins 11, and the fans 14 are disposed on the outer sides of the corresponding cooling fins 13, so as to provide timely cooling during the cooling process, thereby preventing the semiconductor cooling fins 11 from being damaged.
As shown in fig. 3A and 3B, when the test seawater at normal temperature flows through the flat conduit 12, the semiconductor cooling plate 11 absorbs a part of the heat, so as to lower the temperature of the flat conduit 12, thereby achieving the effect of temperature control. It is worth mentioning that the heat absorbed by the semiconductor chilling plates 11 is exhausted to the outside through the heat sink 13 and the fan 14, so as to prevent the chilling structures of the semiconductor chilling plates 11 from being damaged.
In addition, it is worth mentioning that the heat dissipation fins 13 are adhered to the corresponding semiconductor cooling fins 11 by heat conductive glue 15, and the fans 14 are fixed to the corresponding heat dissipation fins 13 by means of screws.
In addition, it is worth mentioning that in order to reduce the heat exchange between the refrigeration device 10 and the outside as much as possible and avoid the problem of inaccurate temperature control, the portion of the flat conduit exposed in the air is covered with heat insulation cotton. The conduit part from the outlet of the refrigerating device 10 to the seawater inlet of the microfluidic chip experiment is wrapped with heat insulation cotton, and heat insulation can be performed in other ways, and the invention is not limited.
Further, in the preferred embodiment of the present invention, the load end of the temperature controller 30 is connected in parallel to the two semiconductor chilling plates 11, so that the temperature controller 30 can control the temperature of the flat type conduit 12 by controlling the operation of the semiconductor chilling plates 11, thereby controlling the temperature of the experimental seawater flowing into the microfluidic culturing chip 50.
Specifically, the temperature controller 30 in the present invention is used to control the fluctuation range of the temperature, and the fluctuation range can be set manually, i.e. the temperature range can be set manually, the present invention uses the XH-type digital temperature controller 30 to control the temperature range, and the XH-type digital temperature controller 30 has the advantages of convenient installation, simple wiring, settable start and stop temperatures, high precision, long service life, low price, etc., and can completely replace mechanical temperature control and has a delayed start function.
The temperature controller 30 adopted by the invention is an XH-W1315 type digital temperature controller 30, the temperature measuring and controlling range is between-50 ℃ and 110 ℃, the input power supply 40 is supplied by 12V direct current, the appearance size is 79 x 54 x 21mm, and as shown in figure 4, the requirement of appropriate occupied space is met. Correspondingly, the power supply 40 of the present invention is set as a 12V dc power supply 40 for dc power supply to the temperature controller 30. Because the volume of the temperature-controlled object is small, and the provided temperature-measuring area is limited, the temperature-sensing probe 20 adopts a superfine thermocouple wire, the diameter can reach 0.08-0.1 mm, and a waterproof head, a water drop head, a magnetic head and the like can be selected according to the situation with lower requirements, namely the temperature-sensing probe 20 can be any one of the waterproof head, the water drop head, the magnetic head and the thermocouple wire. Preferably, in this embodiment of the present invention, a thermocouple wire is used to detect the temperature of the microfluidic culture chip, and since the thermocouple wire is ultra-fine, the observation of the inside of the microfluidic culture chip 50 by a microscope is not affected.
Specifically, the temperature control process of the independent temperature control system of the microfluidic culture chip is as follows: one end of the thermocouple wire is connected with the temperature controller 30 in a conducting way, and the other end of the thermocouple wire is arranged below the inner liquid level of the microfluidic culture chip, so that the temperature of the experimental seawater in the microfluidic culture chip 50 can be observed on the display screen 31 of the temperature controller 30 in real time, and when the temperature of the experimental seawater in the microfluidic culture chip 50 is lower than the set temperature range, the temperature controller 30 controls the semiconductor refrigerating sheet 11 to stop working, namely stop refrigerating; when the temperature of the experimental seawater in the microfluidic culture chip 50 is greater than the set temperature range, the temperature controller 30 controls the semiconductor refrigeration sheet 11 to refrigerate, so that the temperature of the experimental seawater returns to the set temperature range again, and the accurate control of the chamber temperature of the microfluidic culture chip is realized.
FIG. 4 is a wiring diagram of the temperature controller 30 of the present invention, wherein the temperature controller 30 is electrically connected to a 12V DC power source 40, the power source 40 is selected to provide the maximum current allowed to pass through, and the physical formula is
In particular, the independent temperature control system of the microfluidic culture chip of the present invention can independently control the temperature of the microfluidic culture chips 50 of multiple units through the multiple temperature controllers 30, the multiple temperature-sensitive probes 20, and the multiple refrigeration devices 10. Based on different temperature ranges set by different temperature controllers 30, the independent temperature control system of the microfluidic culture chip can meet the temperature requirements of the microfluidic culture chips of different units.
Specifically, as shown in fig. 1 to 5B, the specific implementation of the independent temperature control system of the microfluidic culture chip of the present invention is used for controlling the temperature of the microfluidic culture chip of multiple units is illustrated. In this embodiment of the present invention, the temperature-controlled objects of the present invention are 4 microfluidic culture chips 50 made by sealing PDMS (polydimethylsiloxane) material to a glass slide, the cultured organisms are jellyfish or algae, fig. 5A and 5B are schematic structural diagrams of the microfluidic culture chips 50, the chamber size of the microfluidic culture chip is 5 x 4mm, the temperature control is required to be between 8 and 15 ℃, and according to the experimental requirements, the temperature control is required to be independent for four microfluidic culture chips 50 to observe the influence of the temperature on the organisms, so 1 12V of the power supply 40, 4 of the temperature controller 30 with the model number of XH-W1315, 8 of the semiconductor chilling plates 11 with the block size of 40 x 40mm, 8 of the semiconductor chilling plates 11 with the block size of 80 x 40mm, 2 of the heat dissipation plates 13 with the block size of 80 x 40mm, 2 of the fans 14 with the block size of 80 x 80mm, 4 of the flat conduits 12, 4 water outlet pipes with common shapes, 4 superfine thermocouple wires, 4 micro-flow pumps and corresponding power supplies 40, 151 bottles of heat conducting glue and a plurality of wires.
It should be understood that, in this embodiment of the present invention, the size of the chamber of the microfluidic culture chip, the size of the semiconductor chilling plate 11, the size of the heat sink 13 and the size of the fan 14 are only for illustration and should not be construed as limiting the present invention.
Further, 4 temperature controllers 30 are connected in parallel to the power source 40, the load end of each temperature controller 30 is connected in parallel to two corresponding semiconductor chilling plates 11, and the flat conduit 12 and the two heat dissipation plates 13 are bonded to the corresponding semiconductor chilling plates 11 through the heat conductive adhesive 15, as shown in fig. 3B. And then the 2 fans 14 are respectively fixed on the outer sides of the corresponding radiating fins 13 through nuts and are connected with the power supply 40. And 4 superfine thermocouple wires are respectively connected to the sensing end of the temperature controller 30, and the other end of the temperature controller is placed below the liquid level of the experimental seawater through the feeding port 51 of the microfluidic culture chip. After the water inlet conduit is connected with the micro-flow pump, one end of the water inlet conduit is connected with the buffer bottle, the other end of the water inlet conduit is inserted into the cavity of the micro-flow control culture chip 50, one end of the water outlet conduit is connected with the waste liquid bottle, and the other end of the water outlet conduit is inserted into the cavity of the micro-flow control culture chip 50.
It should be noted that the water inlet conduit is inserted into the chamber of the microfluidic culture chip 50 through the water inlet of the microfluidic culture chip 50, and the water outlet conduit is inserted into the chamber of the microfluidic culture chip 50 through the water outlet of the microfluidic culture chip 50, that is, the microfluidic culture chip 50 is provided with the experimental seawater inlet/outlet 52.
It is also worth mentioning that the experimental seawater used in the present invention is a liquid having parameters such as specific PH value and dissolved oxygen amount. Finally, temperature fluctuation ranges can be set, for example, the temperature ranges set for the microfluidic culture chip 50 of 4 units are respectively: the temperature ranges set by the temperature controller 30 are respectively 8-10 ℃, 10-12 ℃, 12-14 ℃ and 14-16 ℃, and correspondingly: 8-10 ℃, 10-12 ℃, 12-14 ℃ and 14-16 ℃. And finally, the power supply 40 is turned on, and when the temperature-sensitive probe 20 detects that the temperature of the experimental seawater in the microfluidic culture chip 50 is higher than the set upper limit of the temperature range in real time, the temperature controller 30 controls the semiconductor refrigeration sheet 11 to start refrigeration until the temperature-sensitive probe 20 detects that the temperature of the experimental seawater in the microfluidic culture chip 50 is within the temperature range.
That is to say, in this embodiment of the present invention, the independent temperature control system of the microfluidic culture chip includes four of the refrigeration devices 10 and four of the temperature controllers 30, the four of the temperature controllers 30 are connected in parallel to the power supply 40 for independently controlling the temperature of the experimental seawater in the four independent microfluidic culture chips 50, and the temperature ranges preset by the four temperature controllers 30 are: 8-10 ℃, 10-12 ℃, 12-14 ℃ and 14-16 ℃.
Therefore, it can be understood that the invention forms four complete temperature control systems with feedback regulation function by respectively refrigerating the experimental seawater in the inlet ducts of the microfluidic culture chips of each unit, can realize the independent control of the chamber temperature of the microfluidic culture chips, and can achieve the purpose of stably and accurately controlling the temperature by selecting the appropriate flow velocity of the experimental seawater without affecting the observation path of the microscope. The independent temperature control system of the microfluidic culture chip is simple to operate, has low requirements on the technical level of platform users, and is simple and easy to operate.
It can also be understood that, in the present invention, the semiconductor refrigeration sheets 11 are connected to the temperature controller 30, the flat conduit 12 with a special shape (flat shape) is disposed between the two semiconductor refrigeration sheets 11 and is fixed by the heat conducting glue 15, and this method reduces the contact area between the experimental seawater and the air, and greatly reduces the extra power consumption. And the heat radiating fins 13 and the fan 14 are arranged outside the semiconductor refrigerating fins 11, so that a heat radiating device is added, and the normal operation of the refrigerating device 10 is ensured. The temperature sensing probe 20 transmits a negative feedback signal back to the temperature controller 30 in real time, the temperature controller 30 makes a further judgment on whether the semiconductor chilling plate 11 works or not according to the negative feedback signal of the temperature sensing probe 20 in real time, and the design of combining positive feedback and negative feedback can ensure accurate control of temperature.
It should be understood that the independent temperature control system of the microfluidic culture chip of the present invention can be used for independent temperature control of two, three, four, five, and more than five microfluidic culture chips 50, that is, the present invention does not limit the number of the refrigeration devices 10, the temperature-sensitive probes 20, and the temperature controllers 30 of the independent temperature control system of the microfluidic culture chip.
The invention also provides a temperature control method of the microfluidic culture chip in another aspect, which comprises the following steps:
(a) detecting the temperature of the experimental seawater in the microfluidic culture chip 50 in real time through the temperature-sensitive probe 20; and
(b) based on the feedback of the temperature probe 20 to the temperature of the experimental seawater in the microfluidic culture chip 50, the temperature-sensing controller controls the operation of the refrigerating device 10.
It should be noted that, in the step (b), the temperature range is preset in the temperature-sensitive controller, and when the temperature-sensitive probe 20 detects that the temperature of the experimental seawater in the microfluidic culture chip 50 exceeds the temperature range, the temperature-sensitive controller controls the refrigeration device 10 to refrigerate.
It is also worth mentioning that in the step (b), when the temperature of the experimental seawater detected by the temperature-sensitive probe 20 in the microfluidic culture chip 50 is lower than the temperature range, the temperature-sensitive controller controls the refrigeration device 10 to stop refrigerating.
In particular, the temperature range set by the temperature-sensitive controller is: 8-16 ℃.
The technical features of the above embodiments can be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, but should be considered as the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above examples only express preferred embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (15)
1. Independent temperature control system of micro-fluidic culture chip, its characterized in that includes:
at least one refrigerating device, wherein the refrigerating device is used for refrigerating the experiment seawater dynamically updated in real time of the microfluidic culture chip;
the temperature controller is electrically connected with the refrigerating device; and
the two ends of the temperature-sensing probe are respectively arranged on the microfluidic culture chip and the temperature controller and are used for detecting the temperature of the experimental seawater in the microfluidic culture chip in real time and sending a feedback signal to the temperature controller, and the temperature controller controls the work of the refrigerating device based on the feedback signal sent by the temperature-sensing probe, so that the temperature of the experimental seawater dynamically updated in real time is kept in the temperature range set by the temperature controller;
the refrigerating device comprises two semiconductor refrigerating pieces and a flat conduit, wherein the two semiconductor refrigerating pieces are in conductive connection with the temperature controller, the flat conduit is arranged between the two semiconductor refrigerating pieces, the flat conduit is connected with an experimental seawater bottle and the microfluidic culture chip, the two semiconductor refrigerating pieces are controlled by the temperature controller to refrigerate when being started so as to reduce the temperature of the flat conduit, the temperature of the experimental seawater flowing through the flat conduit is reduced, the flat conduit is made of metal aluminum, the two semiconductor refrigerating pieces are adhered to the flat conduit through heat-conducting glue, the size of each semiconductor refrigerating piece is set to be larger than or equal to that of the flat conduit, and the part of the flat conduit exposed in the air is covered with heat-insulating cotton.
2. The independent temperature control system for microfluidic culture chips according to claim 1, wherein the cooling device further comprises two cooling fins and two fans, the cooling fins are disposed on the outer sides of the corresponding semiconductor cooling fins, and the fans are disposed on the outer sides of the corresponding cooling fins.
3. The independent temperature control system for the microfluidic culture chip according to claim 2, wherein the heat dissipation plate is adhered to the corresponding semiconductor cooling plate by a heat conductive adhesive, the fan is fixed to the corresponding heat dissipation plate by screws, and the heat dissipation plate and the fan are larger than the semiconductor cooling plate.
4. The independent temperature control system of the microfluidic culture chip according to any one of claims 1 to 3, further comprising a power supply, wherein the power supply is electrically connected to the refrigerating device and the temperature controller, when the power supply is activated, the temperature-sensing probe detects the temperature of the experimental seawater in the microfluidic culture chip in real time, when the temperature-sensing probe detects that the temperature of the experimental seawater in the microfluidic culture chip exceeds the temperature range, the temperature controller controls the refrigerating device to refrigerate, and when the temperature-sensing probe detects that the temperature of the experimental seawater in the microfluidic culture chip is lower than the temperature range, the temperature controller controls the refrigerating device to stop refrigerating.
5. The independent temperature control system of the microfluidic culture chip according to claim 4, wherein the temperature-sensing probe is provided as any one of a waterproof head, a water drop head, a magnetic head and a thermocouple wire.
6. The independent temperature control system of the microfluidic culture chip according to claim 4, wherein the temperature controller is set as a digital temperature controller with model number XH-W1315.
7. The independent temperature control system of the microfluidic culture chip according to claim 4, wherein the temperature controller comprises a display screen for real-time observation of the temperature of the experimental seawater in the microfluidic culture chip detected by the temperature-sensitive probe in real time.
8. The independent temperature control system of the microfluidic culture chip according to claim 4, wherein the power supply is configured as a 12V DC power supply.
9. The independent temperature control system of microfluidic culture chips of claim 4, wherein the temperature range set by the temperature controller is set as: 8-16 ℃.
10. The independent temperature control system of the microfluidic culture chip according to claim 4, wherein the independent temperature control system of the microfluidic culture chip comprises four of the refrigeration devices and four of the temperature controllers, and the four temperature controllers are connected in parallel to the power supply to independently control the temperature of the experimental seawater in the microfluidic culture chip of four independent units.
11. The independent temperature control system of microfluidic culture chips according to claim 10, wherein the temperature ranges set by the four temperature controllers are respectively: 8-10 ℃, 10-12 ℃, 12-14 ℃ and 14-16 ℃.
12. The temperature control method of the independent temperature control system of the microfluidic culture chip according to any one of claims 1 to 11, comprising the following steps:
(a) detecting the temperature of the experimental seawater in the microfluidic culture chip in real time through a temperature-sensitive probe; and
(b) based on the feedback of the temperature of the experimental seawater in the microfluidic culture chip by the temperature sensing probe, the temperature sensing controller controls the work of the refrigerating device; the refrigerating device comprises two semiconductor refrigerating pieces and a flat conduit, wherein the two semiconductor refrigerating pieces are in conductive connection with the temperature controller, the flat conduit is arranged between the two semiconductor refrigerating pieces, the flat conduit is connected with an experimental seawater bottle and the microfluidic culture chip, the two semiconductor refrigerating pieces are controlled by the temperature controller to refrigerate when being started so as to reduce the temperature of the flat conduit, the temperature of the experimental seawater flowing through the flat conduit is reduced, the flat conduit is made of metal aluminum, the two semiconductor refrigerating pieces are adhered to the flat conduit through heat-conducting glue, the size of each semiconductor refrigerating piece is set to be larger than or equal to that of the flat conduit, and the part of the flat conduit exposed in the air is covered with heat-insulating cotton.
13. The method of claim 12, wherein in the step (b), the temperature controller is set to have a temperature range, and when the temperature probe detects that the temperature of the experimental seawater in the microfluidic culture chip exceeds the temperature range, the temperature controller controls the refrigerating device to refrigerate.
14. The method of claim 13, wherein in the step (b), when the temperature-sensing probe detects that the temperature of the experimental seawater in the microfluidic culture chip is lower than the temperature range, the temperature-sensing controller controls the refrigeration device to stop refrigeration.
15. The method according to claim 13 or 14, wherein the temperature range is: 8-16 ℃.
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