Gene chip constant temperature fixing device and control method thereof

Abstract

The application discloses a constant-temperature fixing device for a gene chip and a control method thereof. The constant-temperature fixing device comprises a plurality of constant-temperature positioning devices. Each constant-temperature positioning device comprises a chip mounting area, a constant-temperature flow channel and a temperature control assembly arranged in sequence from a first side to a second side. A temperature measuring assembly comprises a temperature sensor arranged on the accommodating position for detecting the temperature of the accommodating position. A circulating water pump comprises an inlet and an outlet. A circulating flow channel is arranged between the inlet and the outlet. The plurality of constant-temperature flow channels are arranged in series or in parallel on the circulating flow channel. A buffer assembly comprises a buffer bottle arranged between the liquid outlet of the constant-temperature flow channel and the inlet of the circulating water pump. A temperature controller is arranged. The constant-temperature fixing device has high integration, can be flexibly regulated and controlled and responds quickly. The temperature overshoot phenomenon in the temperature regulation process is effectively reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of gene chip constant temperature fixing device, in particular to a constant temperature fixing device for gene chip and a control method thereof. BACKGROUND

[0002] Gene chip technology is a high-throughput detection method widely used in gene expression analysis, mutation detection and polymorphism research. Staining and washing of gene chips are key steps to obtain high-quality data. In the staining process of the sample preparation stage, the extracted total RNA is usually transcribed into cDNA with fluorescent labels by reverse transcriptase for subsequent hybridization and signal detection. The washing process is used to remove unbound or non-specific hybridized cDNA to improve signal-to-noise ratio and detection accuracy. Both steps need to be carried out under strict temperature control conditions, usually requiring temperature fluctuations within ±0.5℃, otherwise it will seriously affect the reliability and repeatability of the experimental results.

[0003] The existing temperature control means is to use a constant temperature reaction bath system to provide a constant temperature environment for the chip fixing device by circulating hot water. However, this type of constant temperature tank still has the following defects: first, the constant temperature reaction bath equipment occupies a large space, which is not conducive to the construction of integrated and high-throughput experimental environment; second, the water volume in the reaction bath is large, and temperature overshoot phenomenon is easy to occur during heating and cooling, resulting in a decrease in control accuracy; third, there is a temperature difference between the internal temperature sensor of the reaction bath and the area where the chip is placed, causing actual temperature control deviation; fourth, the cooling relies on the compressor refrigeration, which is slow and has serious overshoot, making it difficult to meet the experimental requirements of rapid temperature change; finally, the traditional constant temperature bath usually does not have flexible programmed temperature control capability, and cannot adapt to diversified experimental processes.

[0004] The invention patent with publication number CN118131838A discloses a constant temperature control system of a liquid constant temperature tank, which comprises a constant temperature tank, a semiconductor heat exchanger, a water pump, a temperature controller and a control board. The circulating water outlet of the constant temperature tank is connected to the circulating water inlet of the constant temperature tank through the water pump and the semiconductor heat exchanger. A temperature sensor is arranged in the constant temperature tank, and the temperature sensor is connected to the control board through the temperature controller. The control board controls the semiconductor refrigerating plate connected to the water pump and the semiconductor heat exchanger. The real-time temperature collected by the temperature sensor in the constant temperature tank is transmitted to the temperature controller, and the temperature controller compares the set temperature value and outputs a switching signal to the control board. The control board realizes positive and negative power output through an H-bridge switching circuit, thereby controlling the semiconductor heat exchanger to refrigerate and heat the circulating water. Compared with the traditional constant temperature tank, the temperature control precision is improved. However, since it still uses a constant temperature tank to control the temperature of the chip, the water volume in the constant temperature tank is large, and therefore the problems of temperature overshoot and slow temperature change cannot be avoided.

[0005] Therefore, it is urgent to develop a system with high integration, accurate temperature control, rapid response and flexible temperature control to overcome the deficiencies of the prior art in gene chip temperature control processing. SUMMARY

[0006] Therefore, to solve the above problems, the application provides a constant temperature fixing device for a gene chip and a control method thereof.

[0007] The application is implemented by the following technical solutions:

[0008] The constant temperature fixing device for a gene chip comprises:

[0009] A plurality of constant temperature positioning devices, each constant temperature positioning device comprising a chip mounting area, a constant temperature flow channel and a temperature control assembly arranged in sequence from a first side to a second side, the chip mounting area comprising a plurality of accommodation positions for placing gene chips, the constant temperature flow channel comprising an inlet and an outlet, and the constant temperature flow channel passing through the second side of each accommodation position in sequence, the temperature control assembly being used for temperature regulation of the medium in the constant temperature flow channel, and the medium in the constant temperature flow channel uniformly conducting temperature to each accommodation position;

[0010] A temperature measurement assembly comprising a temperature sensor arranged on the accommodation position for detecting the temperature of the accommodation position;

[0011] A circulating water pump comprising an inlet and an outlet, a circulating flow channel being arranged between the inlet and the outlet of the circulating water pump, and the constant temperature flow channels in the plurality of constant temperature positioning devices being arranged in series or in parallel on the circulating flow channel;

[0012] A buffer assembly comprising a buffer bottle arranged between the outlet of the constant temperature flow channel and the inlet of the circulating water pump;

[0013] A temperature controller for controlling the temperature control assembly to achieve constant temperature control of the constant temperature flow channel, and the temperature control assembly being signal connected with the temperature controller.

[0014] Preferably, the constant temperature flow channels of the plurality of constant temperature positioning devices are arranged in series on the circulating flow channel, the outlet of the circulating water pump is connected to the inlet of the constant temperature flow channel of the first constant temperature positioning device, the outlet of the constant temperature flow channel of the last constant temperature positioning device is connected to the inlet of the buffer bottle, and the outlet of the buffer bottle is connected to the inlet of the circulating water pump.

[0015] Preferably, the constant temperature flow channels of the plurality of constant temperature positioning devices are arranged in parallel on the circulating flow channel, the inlet of each constant temperature flow channel is connected to the outlet of the circulating water pump, the outlet of each constant temperature flow channel is connected to the inlet of the buffer bottle, and the outlet of the buffer bottle is connected to the inlet of the circulating water pump.

[0016] Preferably, each constant temperature positioning device comprises a first positioning plate and a second positioning plate, a first side of the first positioning plate forms a chip mounting area, and a plurality of accommodation positions are arranged at equal intervals along the length direction of the chip mounting area, a second side of the first positioning plate is arranged with a flow channel groove in a meandering manner, and the arrangement area of the flow channel groove on the second side of each accommodation position is consistent, a starting end of the flow channel groove is communicated with the liquid inlet, and a terminal end of the flow channel groove is communicated with the liquid outlet, the second positioning plate is arranged on the second side of the first positioning plate, and a constant temperature flow channel is formed between the first side of the second positioning plate and the flow channel groove.

[0017] Preferably, a plurality of conduction grooves are further arranged in the flow channel groove, the conduction grooves are located on the second side of each accommodation position, a first side of the second positioning plate is provided with a plurality of conduction blocks, the conduction blocks correspond to the conduction grooves one by one and are arranged at intervals, and a longitudinal bending part is formed at the interval between the conduction blocks and the conduction grooves.

[0018] Preferably, the constant temperature positioning device further comprises a third positioning plate, a first side of the third positioning plate is connected with a second side of the second positioning plate, and the first side of the third positioning plate is provided with a positioning groove, and the temperature control assembly is fixed in the positioning groove.

[0019] Preferably, the constant temperature positioning device further comprises a heat dissipation mechanism, the heat dissipation mechanism comprises a heat dissipation fan and a heat dissipation plate connected with the third positioning plate, a first side of the heat dissipation plate forms a heat dissipation channel, and an inlet of the heat dissipation channel is communicated with an outlet of the heat dissipation fan.

[0020] Preferably, a first limiting part is arranged on the first side of the second positioning plate, a first limiting groove matched with the limiting part is arranged on the second side of the first positioning plate, a plurality of bosses are further arranged on the first limiting part, a limiting hole corresponding to the boss is further arranged on the second side of the first positioning plate, a sealing glue layer is arranged between the first limiting part and the first limiting groove and between the boss and the limiting hole, a second limiting part is arranged on the second side of the third positioning plate, a second limiting groove matched with the second limiting part is arranged on the first side of the heat dissipation plate, a sealing glue layer is arranged between the second limiting part and the second limiting groove, and the first positioning plate, the second positioning plate, the third positioning plate and the heat dissipation plate are riveted by screws.

[0021] The control method of the constant temperature fixing device for gene chips adopts the constant temperature fixing device for gene chips as described above, and comprises the following steps:

[0022] The circulating water pump is turned on, and the medium is circulated and circulated in the circulating flow channel and the constant temperature flow channel of each constant temperature positioning device;

[0023] Setting a target temperature, and determining a maximum allowable temperature and a minimum allowable temperature according to the target temperature;

[0024] An initial temperature of the accommodating position is acquired, a first constant temperature control on the medium in the constant temperature flow channel is performed based on the initial temperature of the accommodating position by using a temperature control component, and a target temperature is taken as a constant temperature setting value, the temperature control component is controlled by a temperature controller, and the temperature of the medium in the constant temperature flow channel gradually approaches the constant temperature setting value;

[0025] The actual temperature of the accommodating position is collected in real time by the temperature sensor, and a temperature curve is drawn according to the actual temperature, a first peak value of the temperature curve is recorded, and a temperature difference AW of the peak value and the maximum allowable temperature is calculated;

[0026] After the first constant temperature control is ended, the initial temperature of the accommodating position is called, a second constant temperature control on the medium in the constant temperature flow channel is performed based on the initial temperature of the accommodating position by using the temperature control component, and a temperature obtained by subtracting AW from the target temperature is taken as the constant temperature setting value;

[0027] The actual temperature of the accommodating position is collected in real time by the temperature sensor, and a temperature curve is drawn according to the actual temperature, when a first peak value of the temperature curve appears, the constant temperature setting value is reset to the target temperature, and the chips are placed on the accommodating position one by one.

[0028] The beneficial effects of the technical scheme of the present application mainly include:

[0029] 1. The constant temperature positioning device replaces the traditional large constant temperature tank by adopting the upper and lower chip mounting areas, the constant temperature flow channel and the temperature control component, on the one hand, the land area is significantly reduced, and the integration of the chip constant temperature control system is improved, on the other hand, the constant temperature flow channel is uniformly arranged between the chip mounting area and the temperature control component, which can significantly reduce the actual temperature control deviation, and at the same time, ensure that the temperature of each accommodating position on the chip mounting area is consistent, and at the same time, due to the reduction of the volume of the medium of the whole system, combined with the high-precision temperature control of the temperature controller and the circulation control of the medium in the constant temperature flow channel by the small circulating water pump, a flexible and rapid constant temperature control system is realized, and the temperature overshoot phenomenon in the temperature regulation process is effectively weakened.

[0030] 2、In the constant temperature fixing device for gene chip, the flow path of the constant temperature flow channel is narrow, which facilitates the high-density and uniform arrangement of the second side of the chip mounting area, and a buffer bottle is arranged between the outlet of the constant temperature flow channel and the inlet of the circulating water pump. Before the system starts, there may be some air in the constant temperature flow channel and the circulating flow channel, and the buffer bottle stores some medium, which can ensure that when the medium in the constant temperature flow channel and the circulating flow channel is insufficient, the circulating water pump will not be damaged due to no water and no load. In addition, during the medium circulation process, the local small bubbles in the constant temperature flow channel will enter the buffer bottle with the medium, and the gas-liquid separation is realized in the buffer bottle, so that the bubbles will not enter the constant temperature flow channel through the circulating water pump, avoiding the situation that the local temperature in the constant temperature flow channel is too low due to the existence of local bubbles, and the effect is more obvious with the increase of use time.

[0031] 3、In the control method of the constant temperature fixing device for gene chip, the temperature control assembly is combined with the PID controller to effectively improve the temperature change rate and high-precision adjustment of the medium in the constant temperature flow channel and the accommodation position. The temperature curve of the constant temperature fixing device when the target temperature is controlled is obtained through the first constant temperature control, and the temperature difference AW between the overshoot temperature and the highest allowable temperature is judged according to the temperature curve, so that the temperature difference is automatically compensated by using the segmented temperature control method in the second constant temperature control. According to the overshoot temperature difference compensation strategy, the temperature overshoot can be further inhibited, and the temperature can be ensured to be stable in the set range. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 is a working schematic diagram of the constant temperature fixing device for gene chip when the constant temperature flow channel is connected in series on the circulating flow channel;

[0033] Figure 2 is a working schematic diagram of the constant temperature fixing device for gene chip when the constant temperature flow channel is connected in parallel on the circulating flow channel;

[0034] Figure 3 is a perspective view of the constant temperature fixing device for gene chip;

[0035] Figure 4 is a top view of the constant temperature fixing device for gene chip;

[0036] Figure 5 is a perspective view of the constant temperature fixing device for gene chip in an embodiment of the present application;

[0037] Figure 6 is a top view of the constant temperature fixing device for gene chip in an embodiment of the present application;

[0038] Figure 7 is Figure 6 is a sectional view along A-A in the constant temperature fixing device for gene chip;

[0039] Figure 8is a side view of the constant temperature positioning device in an embodiment of the present application;

[0040] Figure 9 is Figure 8 is a sectional view along B-B in the constant temperature positioning device;

[0041] Figure 10 is Figure 9 is an enlarged view of part C in the constant temperature positioning device;

[0042] Figure 11 is a schematic view of the second side of the first positioning plate in an embodiment of the present application;

[0043] Figure 12 is a perspective view of the second positioning plate in an embodiment of the present application;

[0044] Figure 13 is a perspective view of the heat dissipation plate in an embodiment of the present application;

[0045] Figure 14 is a comparison chart of the temperature curves of the first constant temperature control and the second constant temperature control in the control method of the constant temperature positioning device for gene chips. DETAILED DESCRIPTION

[0046] In order to make the objects, advantages and features of the present application more clearly and specifically, the following non-limiting description of the preferred embodiments will be illustrated and explained by means of the accompanying drawings. The embodiments are only typical examples of the application of the technical solutions of the present application, and any technical solutions formed by equivalent replacement or equivalent transformation shall fall within the scope of the present application.

[0047] It is declared that, in the description of the scheme, it is necessary to explain that the terms "center", "upper", "lower", "left", "right", "front", "rear", "inner", "outer" and the like indicate the orientation or position relationship based on the orientation or position relationship shown in the drawings, and are only for the convenience of description and simplification of the description, and do not indicate or imply that the indicated device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application.

[0048] In addition, the terms "first" and "second" in the present scheme are only for the purpose of description, and cannot be understood as indicating or implying the order of importance, or implicitly indicating the number of the indicated technical features. Therefore, the features limited by "first" and "second" can explicitly or implicitly include one or more of the features. In the present application, the meaning of "multiple" is two or more, unless otherwise specifically limited.

[0049] The present application discloses a constant temperature positioning device for gene chips, as shown in Figure 3 , Figure 4 , comprising:

[0050] Multiple constant temperature positioning devices 1, such as Figures 5-8 As shown, each constant temperature positioning device 1 includes a chip mounting area, a constant temperature flow channel 105, and a temperature control component 6 arranged sequentially from the first side to the second side. The chip mounting area includes multiple placement positions 1011 for placing gene chips. The constant temperature flow channel 105 includes an inlet 1051 and an outlet 1052, and the constant temperature flow channel 105 passes through the second side of each placement position 1011 in sequence. The temperature control component 6 is used to regulate the temperature of the medium in the constant temperature flow channel 105. When the medium flows along the constant temperature flow channel 105, it flows evenly through the second side of each placement position 1011 and conducts temperature evenly to each placement position 1011. The medium can be water or other existing coolant. In this embodiment, the medium is preferably coolant to avoid algae clogging the flow channel or scale affecting heat transfer after water has been used for a long time. The temperature control component 6 can be an existing semiconductor cooling / heating chip or other temperature control component 6 that has both cooling and heating functions, which will not be described in detail here.

[0051] The constant temperature fixing device also includes a temperature measuring component, which includes a temperature sensor disposed on the receiving position 1011 for detecting the temperature of the receiving position 1011, such as a temperature probe (not shown in the figure) disposed on the receiving position 1011. In some embodiments, since the constant temperature flow channel 105 passes uniformly through the second side of each receiving position 1011, the temperature of each receiving position 1011 is consistent, and only one receiving position 1011 needs to be provided with a temperature probe. In other embodiments, in order to further improve the detection accuracy or provide a redundant temperature measuring component, temperature sensors can be disposed on multiple receiving positions 1011 to avoid detection errors caused by the failure of a single temperature sensor.

[0052] The constant temperature fixing device also includes a circulating water pump 2, which has an inlet and an outlet. A circulation channel 3 is provided between the inlet and outlet of the circulating water pump 2. The constant temperature channels 105 inside the multiple constant temperature positioning devices 1 are connected in series or in parallel on the circulation channel 3, so as to realize the circulation of the medium between the constant temperature channels 105 inside the multiple constant temperature positioning devices 1, the circulation channel 3 and the circulating water pump 2. Since the medium in the entire constant temperature fixing device circulates, the temperature of the medium in the entire constant temperature fixing device is relatively stable after a period of constant temperature control, thereby further ensuring the accuracy of constant temperature control, while reducing the frequency of temperature adjustment and saving energy.

[0053] The constant temperature fixing device further comprises a buffer assembly, the buffer assembly comprises a buffer bottle 4 arranged between the liquid outlet 1052 of the constant temperature flow channel 105 and the inlet of the circulating water pump 2; the buffer bottle 4 stores a part of medium and a part of air, the medium is located at the bottom of the buffer bottle 4, the air is located at the top of the buffer bottle 4, meanwhile, the outlet of the buffer bottle 4 is located at the bottom, and the inlet is located at the top, the inlet of the buffer bottle 4 is connected with the liquid outlet 1052 of the constant temperature flow channel 105, and the outlet of the buffer bottle 4 is connected with the inlet of the circulating water pump 2, therefore, when the medium in the constant temperature flow channel 105 flows into the buffer bottle 4, the medium flows to the bottom of the buffer bottle 4, and the air in the constant temperature flow channel 105 and small air bubbles in the medium rise to the top of the buffer bottle 4, so that the gas-liquid separation is realized in the buffer bottle 4, when the circulating water pump 2 pumps water, the medium at the bottom of the buffer bottle 4 is directly pumped, which avoids the burning of the circulating water pump 2 due to no water and no load, and on the other hand, since the air is retained in the buffer bottle 4, when the circulating water pump 2 pumps water from the buffer bottle 4, the air will not enter the circulating flow channel 3 and the constant temperature flow channel 105, so that the problem that the temperature of the partial area of the constant temperature flow channel 105 is low due to the existence of air bubbles (the specific heat capacity of air is less than that of water) is solved; the specific structure and working principle of the buffer bottle 4 can refer to the existing buffer bottle 4 product, and will not be described here.

[0054] The constant temperature fixing device further comprises a temperature controller 5 for controlling the temperature control assembly 6 to realize the constant temperature control of the constant temperature flow channel 105, the temperature control assembly 6 is signal connected with the temperature controller 5, in a preferred embodiment, the temperature controller 5 can adopt the existing PID control algorithm, such as the existing incremental PID algorithm or the position PID algorithm with anti-integral saturation, the control logic comprises: setting a target temperature, and performing temperature regulation according to the temperature difference between the real-time temperature of the accommodation site 1011 and the target temperature, so that the temperature of the accommodation site 1011 gradually approaches the target temperature, thereby realizing the constant temperature control, which is the prior art and will not be described here.

[0055] As Figure 1As shown in some embodiments, the constant-temperature flow channels 105 of the plurality of constant-temperature positioning devices 1 are arranged in series on the circulating flow channel 3, the outlet of the circulating water pump 2 is connected to the liquid inlet 1051 of the constant-temperature flow channel 105 of the first constant-temperature positioning device 1, the liquid outlet 1052 of the constant-temperature flow channel 105 of the last constant-temperature positioning device 1 is connected to the inlet of the buffer bottle 4, and the outlet of the buffer bottle 4 is connected to the inlet of the circulating water pump 2. In addition, between the plurality of constant-temperature positioning devices 1, the liquid outlet 1052 of the constant-temperature flow channel 105 of the previous constant-temperature positioning device 1 is communicated with the liquid inlet 1051 of the constant-temperature flow channel 105 of the subsequent constant-temperature positioning device 1, so as to ensure that the constant-temperature flow channels 105 of the plurality of constant-temperature positioning devices 1 are connected in series. Specifically, the circulating water pump 2 is placed laterally, and the inlet of the circulating water pump 2 is located downstream of the buffer bottle 4. At this time, the inlet of the circulating water pump 2 is continuously flowed by water, which can reduce the risk of burning of the water pump due to no water empty load. In the above embodiment, a temperature controller 5 can be arranged on each constant-temperature positioning device 1, respectively, for independently controlling the temperature control component 6 on the current constant-temperature positioning device 1, so as to avoid the problem of inconsistent heating caused by different resistance values of different temperature control components 6. When the medium flow rate in the circulating flow channel 3 and the constant-temperature flow channel 105 is fast, the medium flows rapidly in the circulating flow channel 3 and each constant-temperature flow channel 105, so that the medium temperature in different constant-temperature flow channels 105 remains consistent. At this time, the temperature control components 6 of the plurality of constant-temperature positioning devices 1 can also be synchronously controlled by one temperature controller 5. At this time, only a temperature sensor needs to be arranged on the accommodation position 1011 of one of the constant-temperature positioning devices 1, which can save equipment cost and simplify temperature control program.

[0056] As shown in some embodiments, Figure 2 As shown in some embodiments, the constant-temperature flow channels 105 of the plurality of constant-temperature positioning devices 1 are arranged in series on the circulating flow channel 3, the constant-temperature flow channel 105 of the first constant-temperature positioning device 1 is connected to the liquid inlet 1051 of the constant-temperature flow channel 105 of the subsequent constant-temperature positioning device 1, the liquid outlet 1052 of the constant-temperature flow channel 105 of the last constant-temperature positioning device 1 is connected to the inlet of the buffer bottle 4, and the outlet of the buffer bottle 4 is connected to the inlet of the circulating water pump 2. In addition, between the plurality of constant-temperature positioning devices 1, the liquid outlet 1052 of the constant-temperature flow channel 105 of the previous constant-temperature positioning device 1 is communicated with the liquid inlet 1051 of the constant-temperature flow channel 105 of the subsequent constant-temperature positioning device 1, so as to ensure that the constant-temperature flow channels 105 of the plurality of constant-temperature positioning devices 1 are connected in series. Specifically, the circulating water pump 2 is placed laterally, and the inlet of the circulating water pump 2 is located downstream of the buffer bottle 4. At this time, the inlet of the circulating water pump 2 is continuously flowed by water, which can reduce the risk of burning of the water pump due to no water empty load. In the above embodiment, a temperature controller 5 can be arranged on each constant-temperature positioning device 1, respectively, for independently controlling the temperature control component 6 on the current constant-temperature positioning device 1, so as to avoid the problem of inconsistent heating caused by different resistance values of different temperature control components 6. When the medium flow rate in the circulating flow channel 3 and the constant-temperature flow channel 105 is fast, the medium flows rapidly in the circulating flow channel 3 and each constant-temperature flow channel 105, so that the medium temperature in different constant-temperature flow channels 105 remains consistent. At this time, the temperature control components 6 of the plurality of constant-temperature positioning devices 1 can also be synchronously controlled by one temperature controller 5. At this time, only a temperature sensor needs to be arranged on the accommodation position 1011 of one of the constant-temperature positioning devices 1, which can save equipment cost and simplify temperature control program.

[0057] like Figures 5-12 As shown, in some embodiments, each constant temperature positioning device 1 includes a first positioning plate 101 and a second positioning plate 102. A chip mounting area is formed on the first side of the first positioning plate 101, and a plurality of receiving positions 1011 are arranged at equal intervals along the length direction of the chip mounting area. A flow channel groove 1012 is arranged in a meandering manner on the second side of the first positioning plate 101, and the arrangement area of ​​the flow channel groove 1012 on the second side of each receiving position 1011 is consistent. When the medium flows uniformly in the flow channel groove 1012, the temperature on the first side of each receiving position 1011 can be ensured to be consistent. At this time, only one temperature sensor needs to be set in one of the receiving positions 1011. The device can detect the temperature of all accommodating positions 1011 and ensure that the temperature of the chips on different accommodating positions 1011 is consistent. The starting end of the flow channel 1012 is connected to the liquid inlet 1051, and the ending end of the flow channel 1012 is connected to the liquid outlet 1052. The second positioning plate 102 is disposed on the second side of the first positioning plate 101, and a constant temperature flow channel 105 is formed between the first side of the second positioning plate 102 and the flow channel 1012. When the medium in the circulation channel 3 enters the constant temperature flow channel 105 from the liquid inlet 1051, it must flow through the entire constant temperature flow channel 105 before flowing out from the liquid outlet 1052 at the ending end of the flow channel 1012.

[0058] like Figures 7-12As shown in the drawings, in some embodiments, a plurality of conducting grooves 1013 are further arranged in the flow channel groove 1012, and the conducting grooves 1013 are located at the second side of each accommodating position 1011. The first side of the second positioning plate 102 is provided with a plurality of conducting blocks 1021, which correspond to the conducting grooves 1013 one by one and are arranged at intervals, and a longitudinal bending part 1053 is formed at the interval between the conducting block 1021 and the conducting groove 1013. The longitudinal direction refers to the direction perpendicular to the first positioning plate 101. Due to the position of the conducting groove 1013 corresponding to each accommodating position 1011, the longitudinal bending part 1053 is arranged at the second side of each accommodating position 1011. In addition, the longitudinal bending part 1053 is closer to the first side of the first positioning plate 101 than the flow channel groove 1012, so that the medium in the longitudinal bending part 1053 is closer to the chip mounting area, the temperature transfer path of the medium and the accommodating position 1011 is shortened in the longitudinal direction, and the consistency of the temperature of the accommodating position 1011 and the temperature of the medium in the constant-temperature flow channel 105 is further ensured. In addition, the conducting block 1021 and the conducting groove 1013 are arranged correspondingly, so that the flow area distribution of each position of the constant-temperature flow channel 105 is consistent, so as to avoid the situation that part of the liquid does not flow due to the turbulence phenomenon, ensure that the flow rate of the medium in the constant-temperature flow channel 105 is uniform, and thus improve the uniformity of temperature distribution. In an embodiment, the accommodating position 1011 is protrudingly arranged at the first side of the first positioning plate 101. The outer periphery of each accommodating position 1011 is provided with a positioning assembly 8 for positioning the chip, and the chip is fixed on the accommodating position 1011 by the positioning assembly 8. Since the accommodating position 1011 protrudes from the first side of the first positioning plate 101, in order to avoid increasing the distance between the surface of the accommodating position 1011 and the constant-temperature flow channel 105, the conducting groove 1013 extending towards the accommodating position 1011 is arranged in the flow channel groove 1012, so as to shorten the temperature transfer path of the medium in the longitudinal bending part 1053 and the accommodating position 1011, and avoid increasing the temperature difference between the accommodating position 1011 and the medium due to the too long temperature transfer path.

[0059] As shown in the drawings, Figure 7 , Figure 9 In some embodiments, the constant-temperature positioning device 1 further comprises a third positioning plate 103. The first side of the third positioning plate 103 is connected to the second side of the second positioning plate 102, and the first side of the third positioning plate 103 is provided with a positioning groove 1031. The temperature control assembly 6 is fixed in the positioning groove 1031, so that the temperature control assembly 6 is in direct contact with the second side of the second positioning plate 102, and the temperature is conducted to the medium in the constant-temperature flow channel 105 through the second positioning plate 102.

[0060] As shown in the drawings, Figure 3 , Figure 4 ,Figure 8 , Figure 13 As shown, in some embodiments, the constant temperature positioning device 1 further includes a heat dissipation mechanism, which includes a cooling fan 7 and a heat dissipation plate 104 connected to the third positioning plate 103. A heat dissipation channel 1041 is formed on the first side of the heat dissipation plate 104, and the inlet of the heat dissipation channel 1041 is connected to the outlet of the cooling fan 7. The heat dissipation channel 1041 includes a heat dissipation groove that is meanderingly arranged on the first side of the heat dissipation plate 104. The third positioning plate 103 covers the first side of the heat dissipation plate 104, thereby forming a heat dissipation channel 1041 between the heat dissipation groove and the third positioning plate 103. A first through hole 1044 is provided at the end of the heat dissipation plate 104. One end of the first through hole 1044 is connected to the heat dissipation groove, and the other end is connected to... The outlet of the cooling fan 7 is connected, and the end of the heat sink 104 is also provided with a second through hole 1043. The second through hole 1043 is connected to the heat sink. When the cooling fan 7 blows air out of the outlet, the blown air enters the heat dissipation channel 1041 through the first through hole 1044, and flows out through the second through hole 1043 after passing through the entire heat dissipation channel 1041, thereby realizing the heat dissipation function. In a preferred embodiment, an air duct can also be provided between the first through hole 1044 and the outlet of the cooling fan 7, so as to guide the air blown out by the cooling fan 7 into the first through hole 1044. The arrangement and structure of the air duct can refer to the prior art, such as providing a pipe for guiding the airflow between the air outlet of the cooling fan 7 and the first through hole 1044, etc., which will not be described in detail here.

[0061] like Figure 7 , Figure 9 , Figure 12As shown, in some embodiments, the first side of the second positioning plate 102 is provided with a first limiting part 1022, the second side of the first positioning plate 101 is provided with a first limiting groove 1014 matched with the limiting part, the first limiting groove 1014 is arranged around the outer periphery of the flow channel groove 1012, thereby ensuring the sealing performance between the first positioning plate 101 and the second positioning plate 102, avoiding the medium in the constant-temperature flow channel 105 from flowing out, a plurality of bosses 1023 are further arranged on the first limiting part 1022, the second side of the first positioning plate 101 is further provided with a limiting hole 1015 corresponding to the boss 1023, and a sealing rubber layer is arranged between the first limiting part 1022 and the first limiting groove 1014 and between the boss 1023 and the limiting hole 1015, thereby further improving the sealing performance of the connection between the first positioning plate 101 and the second positioning plate 102, the second side of the third positioning plate 103 is provided with a second limiting part 1032, the first side of the heat dissipation plate 104 is provided with a second limiting groove 1042 matched with the second limiting part 1032, and a sealing rubber layer is arranged between the second limiting part 1032 and the second limiting groove 1042, thereby ensuring the sealing performance between the third positioning plate 103 and the heat dissipation plate 104, the sealing rubber layer can be formed by injecting liquid rubber into the gap between the first positioning plate 101 and the second positioning plate 102 and the gap between the third positioning plate 103 and the heat dissipation plate 104, and the first positioning plate 101, the second positioning plate 102, the third positioning plate 103 and the heat dissipation plate 104 are riveted by screws, and in a preferred embodiment, the screws pass through the boss 1023 and the limiting hole 1015 at the same time, for assembling and fixing the first positioning plate 101, the second positioning plate 102, the third positioning plate 103 and the heat dissipation plate 104.

[0062] The application also discloses a control method of the constant-temperature fixing device for gene chips.

[0063] The circulating water pump 2 is started to make the medium circulate in the circulating flow channel 3 and the constant-temperature flow channel 105 of each constant-temperature positioning device 1, in an embodiment, an external water channel can be connected to the circulating flow channel 3 for supplying water to the circulating flow channel 3, when the medium in the external water channel flows into the circulating flow channel 3, the circulating water pump 2 is started to make the medium circulate in the circulating flow channel 3 and the constant-temperature flow channel 105 of each constant-temperature positioning device 1, in the process of pumping water by the circulating water pump 2, the air in the circulating flow channel 3 and the constant-temperature flow channel 105 enters the buffer bottle 4 under the negative pressure of the medium, and the medium at the bottom of the buffer bottle 4 is input into the circulating water pump 2 through the circulating flow channel 3.

[0064] Setting a target temperature, and determining a maximum allowable temperature and a minimum allowable temperature according to the target temperature; wherein the target temperature refers to a target constant temperature that the accommodation site 1011 needs to reach, and the maximum allowable temperature and the minimum allowable temperature refer to a temperature fluctuation range that the accommodation site 1011 allows when the chip is placed on the accommodation site 1011, for example: when the system requires the accommodation site 1011 to fluctuate within ±0.5℃ of the target temperature, then the maximum allowable temperature is the target temperature plus 0.5℃, and the minimum allowable temperature is the target temperature minus 0.5℃.

[0065] Obtaining an initial temperature of the accommodation site, which refers to the temperature of the accommodation site 1011 before temperature regulation, and using the temperature control assembly 6 to perform first constant temperature control on the medium in the constant temperature flow channel 105 based on the initial temperature of the accommodation site, and taking the target temperature as a constant temperature setting value, the temperature control assembly 6 is controlled by the temperature controller 5, for gradually approaching the temperature of the medium in the constant temperature flow channel 105 to the constant temperature setting value, and the temperature controller 5 can use the existing PID control algorithm, which will not be described here.

[0066] The actual temperature of the accommodation site 1011 is collected in real time by the temperature sensor, as shown in FIG. 6, and a temperature curve is drawn according to the actual temperature, and the first peak value of the temperature curve is recorded. Figure 14 As the temperature controller 5 controls the output temperature of the temperature control assembly 6 in real time, and repeatedly adjusts the output temperature of the temperature control assembly 6 by calculating the temperature difference between the actual temperature and the target temperature in real time to compensate for the temperature difference between the actual temperature and the target temperature, therefore, during the temperature regulation process, the temperature curve forms several bands near the target temperature, and as the temperature regulation time increases, the fluctuation range of the bands of the temperature curve gradually decreases and gradually approaches the target temperature. However, due to factors such as thermal inertia and PID parameters, when the output temperature of the temperature control assembly 6 reaches the target temperature, it will not immediately decrease, but will continue to rise until a peak value. Since the fluctuation range of the first band of the temperature curve is the largest, this can cause the first band of the temperature curve to easily exceed the maximum allowable temperature, and at the same time, since the temperature curve is constantly approaching the target temperature, therefore, except for the first band, other bands are not prone to overshoot problems, therefore, the difference between the peak value of the first band and the maximum allowable temperature needs to be calculated, and this temperature difference needs to be compensated for during the next constant temperature control, so as to avoid the overshoot value of the first band.

[0067] When the slope of the temperature curve is 0 for the first time, it means that the first wave band of the temperature curve reaches the peak, at which time the temperature no longer rises, and then the temperature controller 5 controls the temperature control component 6 to reduce the temperature, calculates the temperature difference AW between the peak and the highest allowable temperature, which represents the overshoot temperature of the temperature curve at the first peak, records the overshoot temperature, and compensates for the overshoot temperature by temperature regulation in the next constant temperature control, so as to ensure that the temperature curve always does not exceed the highest allowable temperature.

[0068] After the first constant temperature control is completed, the initial temperature of the holding site is called, as shown in the formula (1), and the temperature control component 6 is used to perform the second constant temperature control on the medium in the constant temperature flow channel 105 based on the initial temperature of the holding site, and the temperature obtained by subtracting AW from the target temperature is used as the constant temperature setting value to compensate for the overshoot temperature of the first wave band. Figure 14

[0069] Figure 14 As shown in the formula (2), the actual temperature of the holding site 1011 is collected in real time by the temperature sensor, and the temperature curve is drawn according to the actual temperature. When the first peak of the temperature curve appears, the constant temperature setting value is reset to the target temperature. Since the temperature curve is not prone to overshoot after passing the first wave band, resetting the constant temperature setting value to the target temperature can ensure that the temperature gradually approaches the target temperature. At the same time, since the temperature controller 5 controls the temperature control component 6 to reduce the temperature after the first peak of the temperature curve appears, resetting the constant temperature setting value to the target temperature can also prevent the valley value of the temperature curve from being lower than the lowest allowable temperature, so as to ensure that the temperature curve is always between the highest allowable temperature and the lowest allowable temperature. Then, the chips are placed one by one on the holding site 1011.

[0070] In an embodiment, before placing the chip, the actual temperature of the holding site 1011 is collected in real time by the temperature sensor. If the actual temperature is between the highest allowable temperature and the lowest allowable temperature, the chip is placed on the holding site 1011. Otherwise, the chip is placed after the actual temperature reaches between the highest allowable temperature and the lowest allowable temperature. In a preferred embodiment, after each chip is placed on the holding site 1011, whether the temperature of the holding site 1011 is lower than the actual temperature before the chip is placed is collected in real time by the temperature sensor to determine whether the chip is in place, and the next chip is placed after the temperature of the holding site 1011 returns to between the highest allowable temperature and the lowest allowable temperature. Otherwise, it is determined that the chip is not in place, and it is necessary to determine whether the chip is placed on the holding site 1011 again. The reasonable interval of the temperature difference between the in-place temperature of the chip and the actual temperature before the chip is placed can be obtained according to repeated experimental detection, which is not described here.

[0071] ​​The present application has various embodiments, and all technical solutions formed by using equivalent transformation or equivalent transformation fall within the protection scope of the present application.

Claims

1. A thermostatic fixation device for gene chips, characterized in that: include: Multiple constant temperature positioning devices (1), each constant temperature positioning device (1) includes a chip mounting area, a constant temperature flow channel (105) and a temperature control component (6) arranged sequentially from a first side to a second side. The chip mounting area includes multiple placement positions (1011) for placing gene chips. The constant temperature flow channel (105) includes an inlet (1051) and an outlet (1052). The constant temperature flow channel (105) passes through the second side of each placement position (1011) in sequence. The temperature control component (6) is used to regulate the temperature of the medium in the constant temperature flow channel (105). The medium in the constant temperature flow channel (105) conducts temperature evenly to each placement position (1011). The temperature measuring assembly includes a temperature sensor disposed on the accommodating position (1011) for detecting the temperature of the accommodating position (1011); The circulating water pump (2) includes an inlet and an outlet. A circulating flow channel (3) is provided between the inlet and outlet of the circulating water pump (2). The constant temperature flow channels (105) inside multiple constant temperature positioning devices (1) are connected in series or in parallel on the circulating flow channel (3). The buffer assembly includes a buffer bottle (4) disposed between the outlet (1052) of the thermostatic flow channel (105) and the inlet of the circulating water pump (2). Temperature controller (5) is used to control the temperature control component (6) to achieve constant temperature control of the constant temperature flow channel (105). The temperature control component (6) is signal connected to the temperature controller (5).

2. The constant temperature fixation device for gene chips according to claim 1, characterized in that: The constant temperature flow channels (105) of multiple constant temperature positioning devices (1) are connected in series on the circulating flow channel (3). The outlet of the circulating water pump (2) is connected to the inlet (1051) of the constant temperature flow channel (105) of the first constant temperature positioning device (1). The outlet (1052) of the constant temperature flow channel (105) of the last constant temperature positioning device (1) is connected to the inlet of the buffer bottle (4). The outlet of the buffer bottle (4) is connected to the inlet of the circulating water pump (2).

3. The constant temperature fixation device for gene chips according to claim 1, characterized in that: The constant temperature flow channels (105) of multiple constant temperature positioning devices (1) are arranged in parallel on the circulation flow channel (3). The inlet (1051) of each constant temperature flow channel (105) is connected to the outlet of the circulation water pump (2), and the outlet (1052) of each constant temperature flow channel (105) is connected to the inlet of the buffer bottle (4). The outlet of the buffer bottle (4) is connected to the inlet of the circulation water pump (2).

4. The constant temperature fixation device for gene chips according to claim 1, characterized in that: Each constant temperature positioning device (1) includes a first positioning plate (101) and a second positioning plate (102). A chip mounting area is formed on the first side of the first positioning plate (101), and multiple accommodating positions (1011) are arranged at equal intervals along the length direction of the chip mounting area. A flow channel groove (1012) is arranged in a meandering manner on the second side of the first positioning plate (101), and the flow channel groove (1012) has the same arrangement area on the second side of each accommodating position (1011). The starting end of the flow channel groove (1012) is connected to the liquid inlet (1051), and the ending end of the flow channel groove (1012) is connected to the liquid outlet (1052). The second positioning plate (102) is set on the second side of the first positioning plate (101), and a constant temperature flow channel (105) is formed between the first side of the second positioning plate (102) and the flow channel groove (1012).

5. The constant temperature fixation device for gene chips according to claim 4, characterized in that: The flow channel (1012) is also provided with a plurality of transmission channels (1013), the transmission channels (1013) are located on the second side of each accommodating position (1011), and the first side of the second positioning plate (102) is provided with a plurality of transmission blocks (1021), the transmission blocks (1021) correspond one-to-one with the transmission channels (1013) and are spaced apart, and a longitudinally curved part (1053) is formed at the interval between the transmission blocks (1021) and the transmission channels (1013).

6. The constant temperature fixation device for gene chips according to claim 4, characterized in that: The constant temperature positioning device (1) further includes a third positioning plate (103), the first side of the third positioning plate (103) is connected to the second side of the second positioning plate (102), and the first side of the third positioning plate (103) is provided with a positioning groove (1031), and the temperature control component (6) is fixed in the positioning groove (1031).

7. The constant temperature fixation device for gene chips according to claim 6, characterized in that: The constant temperature positioning device (1) also includes a heat dissipation mechanism, which includes a cooling fan (7) and a heat dissipation plate (104) connected to the third positioning plate (103). A heat dissipation channel (1041) is formed on the first side of the heat dissipation plate (1041), and the inlet of the heat dissipation channel (1041) is connected to the outlet of the cooling fan (7).

8. The constant temperature fixation device for gene chips according to claim 7, characterized in that: The second positioning plate (102) has a first limiting part (1022) on its first side, and the first positioning plate (101) has a first limiting groove (1014) matching the limiting part on its second side. The first limiting part (1022) also has a plurality of bosses (1023), and the first positioning plate (101) also has limiting holes (1015) corresponding to the bosses (1023) on its second side. The first limiting part (1022) and the first limiting groove (1014) and the bosses (1023) are connected by a first limiting part (1022) and a first limiting groove (1014). A sealing layer is provided between the limiting holes (1015), a second limiting part (1032) is provided on the second side of the third positioning plate (103), a second limiting groove (1042) matching the second limiting part (1032) is provided on the first side of the heat sink (104), a sealing layer is provided between the second limiting part (1032) and the second limiting groove (1042), and the first positioning plate (101), the second positioning plate (102), the third positioning plate (103) and the heat sink (104) are riveted together by screws.

9. A control method for a constant temperature fixation device for gene chips, characterized in that: The use of the constant temperature fixation device for gene chips as described in any one of claims 1-8 includes the following steps: Turn on the circulating water pump (2) to allow the medium to circulate in the circulating flow channel (3) and the constant temperature flow channel (105) of each constant temperature positioning device (1); Set a target temperature, and determine the maximum and minimum allowable temperatures based on the target temperature; The initial temperature of the container is obtained, and the temperature control component (6) is used to perform the first constant temperature control on the medium in the constant temperature channel (105) based on the initial temperature of the container, and the target temperature is used as the constant temperature set value. The temperature control component (6) is controlled by the temperature controller (5) to make the temperature of the medium in the constant temperature channel (105) gradually approach the constant temperature set value. The actual temperature of the accommodating position (1011) is collected in real time by the temperature sensor, and a temperature curve is plotted based on the actual temperature. The first peak of the temperature curve is recorded, and the temperature difference ΔW between the peak and the maximum allowable temperature is calculated. After the first temperature control ends, the initial temperature of the accommodating position is called, and the temperature control component (6) is used to perform a second temperature control on the medium in the constant temperature flow channel (105) based on the initial temperature of the accommodating position, and the temperature after subtracting ΔW from the target temperature is used as the temperature set value. The actual temperature of the accommodating position (1011) is collected in real time by the temperature sensor, and a temperature curve is plotted based on the actual temperature. When the temperature curve shows the first peak, the constant temperature setting value is reset to the target temperature, and the chips are placed one by one on the accommodating position (1011).

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