Constant-temperature fixing device for gene chip and control method of constant-temperature fixing device

Abstract

The invention discloses a constant-temperature fixing device for a gene chip and a control method of the constant-temperature fixing device, the constant-temperature fixing device comprises a plurality of constant-temperature positioning devices, and each constant-temperature positioning device comprises a chip mounting area, a constant-temperature runner and a temperature control assembly which are sequentially arranged from a first side to a second side; the temperature measuring assembly comprises a temperature sensor which is arranged on the accommodating position and is used for detecting the temperature of the accommodating position; the circulating water pump comprises an inlet and an outlet, a circulating flow channel is arranged between the inlet and the outlet, and the plurality of constant-temperature flow channels are arranged on the circulating flow channel in series or in parallel; the 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; and a temperature controller. The constant-temperature fixing device is high in integration level, capable of being flexibly regulated and controlled and rapid in response, and the temperature overshoot phenomenon in the temperature regulation process is effectively weakened.

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: The constant temperature fixing device for the gene chip comprises: 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; A temperature measuring assembly comprising a temperature sensor arranged on the accommodation position and used for detecting the temperature of the accommodation position; 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; 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; A temperature controller used for controlling the temperature control assembly to realize constant temperature control of the constant temperature flow channel, and the temperature control assembly being signal connected with the temperature controller.

[0008] 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 with 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 with the inlet of the buffer bottle, and the outlet of the buffer bottle is connected with the inlet of the circulating water pump.

[0009] 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 with the outlet of the circulating water pump, the outlet of each constant temperature flow channel is connected with the inlet of the buffer bottle, and the outlet of the buffer bottle is connected with the inlet of the circulating water pump.

[0010] 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.

[0011] 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.

[0012] 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.

[0013] 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.

[0014] 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 matched with the boss one by one 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.

[0015] 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: Start the circulating water pump to make the medium circulate in the circulating flow channel and the constant temperature flow channel of each constant temperature positioning device; Set a target temperature, and determine the highest allowable temperature and the lowest allowable temperature according to the target temperature; 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; An 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 between the peak value and a highest allowable temperature is calculated; After the first constant temperature control is completed, 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; An 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 between the peak value and a highest allowable temperature is calculated;

[0016] The beneficial effects of the technical scheme of the present application mainly include: 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, the actual temperature control deviation can be significantly reduced, the temperature of each accommodating position on the chip mounting area is consistent, and the volume of the medium of the whole system is reduced, 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 are combined, so that a constant temperature control system with flexible regulation and control and rapid response is realized, and the temperature overshoot phenomenon in the temperature regulation process is effectively weakened.

[0017] 2. In the constant temperature fixing device for the gene chip, the flow path of the constant temperature flow channel is relatively narrow, the constant temperature flow channel can be arranged on the second side of the chip mounting area in high density and uniformity, a buffer bottle is arranged between the outlet of the constant temperature flow channel and the inlet of the circulating water pump, part of air may exist in the constant temperature flow channel and the circulating flow channel before the system starts, part of the medium is stored in the buffer bottle, the risk that the circulating water pump is burned due to no water and no load when the medium in the constant temperature flow channel and the circulating flow channel is insufficient can be avoided, in addition, in the medium circulation process, local small bubbles in the constant temperature flow channel enter the buffer bottle with the medium, and gas-liquid separation is realized in the buffer bottle, so that the bubbles do not enter the constant temperature flow channel through the circulating water pump, the situation that the local temperature in the constant temperature flow channel is low due to the existence of local bubbles is avoided, and the effect is more obvious with the increase of the use time.

[0018] 3. The control method of the constant temperature fixing device for gene chip, wherein the temperature control component is combined with the PID controller to effectively improve the temperature variation rate and high-precision adjustment of the medium in the constant temperature flow channel and the accommodation site, the temperature curve of the constant temperature fixing device when the constant temperature control is performed at the target temperature is obtained through the first constant temperature control, and the temperature difference AW between the overshoot temperature and the highest allowable temperature is determined according to the temperature curve, so that the temperature difference is automatically compensated by using the segmented temperature control in the second constant temperature control, and 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 interval. BRIEF DESCRIPTION OF DRAWINGS

[0019] 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; 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; Figure 3 is a perspective view of the constant temperature fixing device for gene chip; Figure 4 is a top view of the constant temperature fixing device for gene chip; Figure 5 is a perspective view of the constant temperature fixing device in an embodiment of the present application; Figure 6 is a top view of the constant temperature fixing device in an embodiment of the present application; Figure 7 is a Figure 6 sectional view along A-A in the Figure 8 is a side view of the constant temperature fixing device in an embodiment of the present application; Figure 9 is a Figure 8 sectional view along B-B in the Figure 10 is a Figure 9 enlarged view of part C in the Figure 11 is a schematic view of the second side of the first positioning plate in an embodiment of the present application; Figure 12 is a perspective view of the second positioning plate in an embodiment of the present application; Figure 13 is a perspective view of the heat dissipation plate in an embodiment of the present application; Figure 14 is a comparison diagram of the temperature curves of the first constant temperature control and the second constant temperature control in the control method of the constant temperature fixing device for gene chip. DETAILED DESCRIPTION

[0020] In order to make the purposes, advantages and characteristics of the present application more clearly and specifically, the following non-restrictive description of preferred embodiments will be used to illustrate and explain the present application. The embodiments are only typical examples of applying the technical solutions of the present application, and any technical solutions formed by equivalent replacement or equivalent transformation are within the scope of the present application.

[0021] It is declared that, in the description of the solutions, it is necessary to point out that the terms "center", "upper", "lower", "left", "right", "front", "back", "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 specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application.

[0022] In addition, the terms "first" and "second" in the present solution are only for the purpose of description, and cannot be understood as indicating or implying the ranking of importance, or implicitly indicating the number of the indicated technical features. Therefore, the features defined with "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.

[0023] The present application discloses a constant-temperature fixing device for gene chips, as shown in Figure 3 , Figure 4 , comprising: A plurality of constant-temperature positioning devices 1, as shown in Figures 5-8 , each constant-temperature positioning device 1 comprises a chip mounting area, a constant-temperature flow channel 105 and a temperature control assembly 6 arranged in sequence from a first side to a second side, the chip mounting area comprises a plurality of accommodation positions 1011 for placing gene chips, the constant-temperature flow channel 105 comprises a liquid inlet 1051 and a liquid outlet 1052, and the constant-temperature flow channel 105 sequentially passes through the second side of each accommodation position 1011, the temperature control assembly 6 is used for temperature regulation of the medium in the constant-temperature flow channel 105, when the medium flows along the constant-temperature flow channel 105, it uniformly flows through the second side of each accommodation position 1011 and uniformly conducts temperature to each accommodation position 1011, the medium can use water or other existing cooling liquid, in the present embodiment, the medium preferably uses cooling liquid to avoid algae blocking the flow channel after a long time of water, or scale affecting heat transfer, the temperature control assembly 6 can use existing semiconductor refrigeration / heating sheets, or other temperature control assemblies 6 with refrigeration and heating functions, which are not described here.

[0024] The constant-temperature fixing device further comprises a temperature measuring assembly, which comprises a temperature sensor arranged on the accommodating position 1011 for detecting the temperature of the accommodating position 1011, such as a temperature measuring probe (not shown in the figure) arranged on the accommodating position 1011. In some embodiments, since the constant-temperature flow channel 105 uniformly passes through the second side of each accommodating position 1011, the temperature of each accommodating position 1011 is consistent, and only one temperature measuring probe needs to be arranged on one of the accommodating positions 1011. In other embodiments, in order to further improve the detection accuracy or provide a redundant temperature measuring assembly, a temperature sensor can be arranged on each of the accommodating positions 1011 to avoid detection errors caused by damage to a single temperature sensor.

[0025] The constant-temperature fixing device further comprises a circulating water pump 2, which comprises an inlet and an outlet. A circulating flow channel 3 is arranged between the inlet and the outlet of the circulating water pump 2. The constant-temperature flow channels 105 in the plurality of constant-temperature positioning devices 1 are arranged in series or in parallel on the circulating flow channel 3, so that the medium in the constant-temperature flow channels 105 in the plurality of constant-temperature positioning devices 1 circulates between the circulating flow channel 3 and the circulating water pump 2. Due to the circulation of the medium in the entire constant-temperature fixing device, the temperature of the medium in the entire constant-temperature fixing device is relatively stable after a constant-temperature control period, thereby further ensuring the accuracy of the constant-temperature control and reducing the frequency of temperature adjustment and saving energy consumption.

[0026] The constant-temperature fixing device further comprises a buffer assembly, which 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 portion of the medium and a portion of the air. The medium is located at the bottom of the buffer bottle 4, and the air is located at the top of the buffer bottle 4. At the same time, 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, it flows to the bottom of the buffer bottle 4, and the air and small bubbles in the medium in the constant-temperature flow channel 105 rise to the top of the buffer bottle 4, thereby realizing gas-liquid separation in the buffer bottle 4. When the circulating water pump 2 pumps water, it directly pumps the medium at the bottom of the buffer bottle 4. This avoids the damage of the circulating water pump 2 caused by no water and no load. 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, solving the problem of lower temperature in the part of the constant-temperature flow channel 105 where air bubbles exist (the specific heat capacity of air is less than that of water). The specific structure and working principle of the buffer bottle 4 can refer to the existing buffer bottle 4 products, which will not be described here.

[0027] The constant temperature fixing device also includes a temperature controller 5, which controls 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. In a preferred embodiment, the temperature controller 5 can adopt an existing PID control algorithm, such as an existing incremental PID algorithm or an anti-integral saturation positional PID algorithm. Its control logic includes: setting a target temperature and adjusting the temperature in real time according to the temperature difference between the real-time temperature of the accommodating position 1011 and the target temperature, so that the temperature of the accommodating position 1011 gradually approaches the target temperature, thereby achieving constant temperature control. This is existing technology and will not be described in detail here.

[0028] like Figure 1 As shown, in some embodiments, the thermostatic flow channels 105 of multiple thermostatic 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 thermostatic flow channel 105 of the first thermostatic positioning device 1, and the outlet 1052 of the thermostatic flow channel 105 of the last thermostatic 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. Furthermore, between the multiple thermostatic positioning devices 1, the outlet 1052 of the thermostatic flow channel 105 of the previous thermostatic positioning device 1 is connected to the inlet 1051 of the thermostatic flow channel 105 of the next thermostatic positioning device 1, ensuring that the thermostatic flow channels 105 of the multiple thermostatic positioning devices 1 are connected end-to-end. Specifically, the circulating water pump 2 is placed sideways, and the inlet of the circulating water pump 2 is located downstream of the buffer bottle 4. Water continuously flows through the inlet of the circulating water pump 2, reducing the risk of the pump burning out due to lack of water and no-load operation. In the above embodiment, each constant temperature positioning device 1 can be equipped with a temperature controller 5 to independently control the temperature control component 6 on the current constant temperature positioning device 1, thereby avoiding the problem of inconsistent heat generation 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 multiple constant temperature positioning devices 1 can also be synchronously controlled by a temperature controller 5. At this time, only a temperature sensor needs to be set on the receiving position 1011 of one of the constant temperature positioning devices 1, which can save equipment costs and simplify the temperature control procedure.

[0029] like Figure 2As shown in the figure, in some embodiments, the constant-temperature flow channel 105 of each constant-temperature positioning device 1 is connected to the outlet of the circulating water pump 2, and the outlet of the constant-temperature flow channel 105 is connected to the inlet of the buffer bottle 4. In another embodiment, the constant-temperature flow channels 105 of multiple constant-temperature positioning devices 1 are connected in parallel to the circulating flow channel 3. The inlet of each constant-temperature flow channel 105 is connected to the outlet of the circulating water pump 2, and the outlet 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 circulating water pump 2. At this time, the outlet of each constant-temperature flow channel 105 of the constant-temperature positioning device 1 is independently connected to the circulating water pump 2, and a buffer bottle 4 is arranged between the outlet of each constant-temperature flow channel 105 and the inlet of the circulating water pump 2. In an embodiment, the outlets of multiple buffer bottles 4 are connected to the inlet of the circulating water pump 2 through a multi-port connector 9. The multi-port connector 9 includes multiple inlet ports corresponding to the outlets of the buffer bottles 4 and an outlet port connected to the inlet of the circulating water pump 2. The outlet of the circulating water pump 2 is also connected to a multi-port connector 9, which includes an inlet port connected to the outlet of the circulating water pump 2 and multiple outlet ports corresponding to the inlets of the constant-temperature flow channels 105. The multi-port connector 9 can be an existing connector product, which is not described here.

[0030] As shown in the figure, Figures 5-12 In some embodiments, each constant-temperature positioning device 1 includes a first positioning plate 101 and a second positioning plate 102. The first side of the first positioning plate 101 forms a chip mounting area, and multiple accommodation sites 1011 are arranged at equal intervals along the length direction of the chip mounting area. The second side of the first positioning plate 101 is arranged with a flow channel groove 1012 in a meandering manner. The arrangement area of the flow channel groove 1012 on the second side of each accommodation site 1011 is consistent. When the medium flows uniformly in the flow channel groove 1012, the temperature on the first side of each accommodation site 1011 is consistent. At this time, only one temperature sensor needs to be arranged in one of the accommodation sites 1011 to detect the temperature of all the accommodation sites 1011, and the temperature of the chips on different accommodation sites 1011 is consistent. The starting end of the flow channel groove 1012 is in communication with the inlet 1051, and the terminal end of the flow channel groove 1012 is in communication with the outlet 1052. The second positioning plate 102 is arranged on the second side of the first positioning plate 101, and the first side of the second positioning plate 102 is in communication with the flow channel groove 1012. When the medium in the circulating flow channel 3 enters the constant-temperature flow channel 105 from the inlet 1051, it must flow through the entire constant-temperature flow channel 105 and then flow out from the outlet 1052 at the terminal end of the flow channel groove 1012.

[0031] As shown in the figure, Figures 7-12As shown, 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 the increase of 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 the increase of the temperature difference between the accommodating position 1011 and the medium due to the too long temperature transfer path.

[0032] As shown in 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.

[0033] As shown in Figure 3 , Figure 4 ,Figure 8 、 Figure 13 As shown in FIG. 7, in some embodiments, the constant temperature positioning device 1 further comprises a heat dissipation mechanism, which comprises a heat dissipation fan 7 and a heat dissipation plate 104 connected with the third positioning plate 103, a first side of the heat dissipation plate 104 is formed with a heat dissipation channel 1041, an inlet of the heat dissipation channel 1041 is in communication with an outlet of the heat dissipation fan 7, wherein the heat dissipation channel 1041 comprises a heat dissipation groove arranged in a meandering manner 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, so as to form the heat dissipation channel 1041 between the heat dissipation groove and the third positioning plate 103, an end of the heat dissipation plate 104 is provided with a first through hole 1044, one end of the first through hole 1044 is in communication with the heat dissipation groove, and the other end is in communication with the outlet of the heat dissipation fan 7, the end of the heat dissipation plate 104 is further provided with a second through hole 1043, the second through hole 1043 is in communication with the heat dissipation groove, when the heat dissipation fan 7 blows air out of the outlet, the blown air enters the heat dissipation channel 1041 from the first through hole 1044, and flows out from the second through hole 1043 after passing through the entire heat dissipation channel 1041, so as to realize the function of heat dissipation; in a preferred embodiment, a wind channel can be further arranged between the first through hole 1044 and the outlet of the heat dissipation fan 7, so as to guide the air blown by the heat dissipation fan 7 into the first through hole 1044, the arrangement and structure of the wind channel can refer to the prior art, such as a pipeline for guiding the direction of air between the outlet of the heat dissipation fan 7 and the first through hole 1044, and the like, which will not be described herein.

[0034] As 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, 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.

[0035] The application further discloses a control method of the constant-temperature fixing device for gene chips. In an embodiment, an external water channel can be connected to the circulating flow channel 3 for supplying water into the circulating flow channel 3, and when the medium in the external water channel flows into the circulating flow channel 3, the circulating water pump 2 is started to circulate the medium in the circulating flow channel 3 and the constant-temperature flow channel 105 of each constant-temperature positioning device 1, and 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.

[0036] A target temperature is set, and a maximum and minimum allowable temperature are determined based on the target temperature. The target temperature refers to the target constant temperature that the accommodating bit 1011 needs to reach. The maximum and minimum allowable temperatures refer to the allowable temperature fluctuation range of the accommodating bit 1011 when the chip is placed on the accommodating bit 1011. For example, when the system requires the accommodating bit 1011 to fluctuate within ±0.5℃ of the target temperature, the maximum allowable temperature is the target temperature plus 0.5℃, and the minimum allowable temperature is the target temperature minus 0.5℃.

[0037] The initial temperature of the accommodating position is obtained. The initial temperature of the accommodating position refers to the temperature of the accommodating position 1011 before temperature regulation. The temperature control component 6 performs the first temperature control on the medium in the constant temperature flow channel 105 based on the initial temperature of the accommodating position, and takes the target temperature as the constant temperature setpoint. The temperature control component 6 is controlled by the temperature controller 5 to make the temperature of the medium in the constant temperature flow channel 105 gradually approach the constant temperature setpoint. The temperature controller 5 can use an existing PID control algorithm, which will not be described in detail here.

[0038] The actual temperature of the accommodating position 1011 is collected in real time by the temperature sensor, such as... Figure 14 As shown, a temperature curve is plotted based on the actual temperature, and the first peak of the temperature curve is recorded. Specifically, since the temperature controller 5 controls the output temperature of the temperature control component 6 in real time and repeatedly adjusts the output temperature of the temperature control component 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, during the temperature regulation process, the temperature curve forms several bands near the target temperature. As the temperature regulation time increases, the fluctuation range of the temperature curve bands gradually decreases and gradually approaches the target temperature. However, due to thermal inertia and PID parameters... Due to factors such as temperature control component 6, when the output temperature reaches the target temperature, it will not immediately cool down, but will continue to rise until a peak value. Since the first band of the temperature curve has the largest fluctuation range, it is easy for the first band of the temperature curve to exceed the maximum allowable temperature. At the same time, since the temperature curve is constantly approaching the target temperature, other bands are less likely to have overshoot problems except for the first band. Therefore, it is necessary to calculate the difference between the peak value of the first band and the maximum allowable temperature, and compensate for this temperature difference in the next constant temperature control to avoid the overshoot value of the first band.

[0039] When the slope of the temperature curve is 0 for the first time, it indicates that the first band of the temperature curve has reached its peak. At this point, the temperature no longer rises. Subsequently, the temperature controller 5 controls the temperature control component 6 to cool down and calculates the temperature difference ΔW between the peak value and the maximum allowable temperature. This temperature difference ΔW represents the overshoot temperature of the temperature curve at the first peak value. This overshoot temperature is recorded and used to compensate for the overshoot temperature through temperature regulation during the next constant temperature control, thereby ensuring that the temperature curve never exceeds the maximum allowable temperature.

[0040] After the first temperature control cycle ends, the initial temperature of the set position is retrieved, such as... Figure 14 As shown, the temperature control component 6 performs a second temperature control on the medium in the constant temperature flow channel 105 based on the initial temperature of the accommodating position, and uses the temperature after subtracting ΔW from the target temperature as the constant temperature set value to compensate for the overshoot temperature of the first band.

[0041] like Figure 14 As shown, 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 reaches its first peak, the constant temperature setpoint is reset to the target temperature. Since the temperature curve is less prone to overshoot after the first band, resetting the constant temperature setpoint to the target temperature ensures that the temperature gradually approaches the target temperature. At the same time, since the temperature controller 5 will control the temperature control component 6 to cool down after the temperature curve reaches its first peak, resetting the constant temperature setpoint to the target temperature at this time can also prevent the valley of the temperature curve from being lower than the minimum allowable temperature, thereby ensuring that the temperature curve is always between the maximum allowable temperature and the minimum allowable temperature. Then, the chips are placed one by one on the accommodating position 1011.

[0042] In one embodiment, before placing a chip, the actual temperature of the receiving position 1011 is collected in real time by a temperature sensor. If the actual temperature is between the maximum and minimum allowable temperatures, the chip is placed on the receiving position 1011; otherwise, the chip is placed after the actual temperature reaches between the maximum and minimum allowable temperatures. In a preferred embodiment, after each chip is placed on the receiving position 1011, the temperature sensor collects in real time whether the temperature at which the chip is placed is lower than the actual temperature before placement to determine whether the chip is in place. The next chip is placed after the temperature of the receiving position 1011 returns to between the maximum and minimum allowable temperatures. Otherwise, the chip is determined not to be in place, and it is necessary to re-determine whether the chip is placed on the receiving position 1011. The reasonable range of temperature difference between the chip's arrival temperature and the actual temperature before placement can be obtained through repeated experiments and will not be elaborated here.

[0043] 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: The application relates to a constant-temperature positioning device for gene chip. The constant-temperature positioning device comprises a plurality of constant-temperature positioning devices (1), each of which comprises a chip mounting area, a constant-temperature flow channel (105) and a temperature control assembly (6) arranged in sequence from a first side to a second side; the chip mounting area comprises a plurality of accommodation positions (1011) for placing gene chips; the constant-temperature flow channel (105) comprises an inlet (1051) and an outlet (1052), and the constant-temperature flow channel (105) passes through the second side of each accommodation position (1011) in sequence; the temperature control assembly (6) is used for temperature regulation of a medium in the constant-temperature flow channel (105); and the medium in the constant-temperature flow channel (105) uniformly conducts temperature to each accommodation position (1011). A temperature measuring assembly comprises a temperature sensor arranged on the accommodation position (1011) and used for detecting the temperature of the accommodation position (1011). A circulating water pump (2) comprises an inlet and an outlet, and a circulating flow channel (3) is arranged between the inlet and the outlet of the circulating water pump (2); the constant-temperature flow channels (105) in the plurality of constant-temperature positioning devices (1) are arranged in series or in parallel on the circulating flow channel (3). A buffer assembly comprises a buffer bottle (4) arranged between the outlet (1052) of the constant-temperature flow channel (105) and the inlet of the circulating water pump (2). A temperature controller (5) is used for controlling the temperature control assembly (6) to realize constant-temperature control of the constant-temperature flow channel (105); the temperature control assembly (6) is signal-connected with the temperature controller (5).

2. The thermostatic fixing device for a gene chip according to claim 1, characterized by: 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 with 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 with the inlet of the buffer bottle (4); and the outlet of the buffer bottle (4) is connected with the inlet of the circulating water pump (2).

3. The thermostatic fixing device for a gene chip according to claim 1, characterized by: The constant-temperature flow channels (105) of the plurality of constant-temperature positioning devices (1) are arranged in parallel on the circulating flow channel (3); the inlet (1051) of each constant-temperature flow channel (105) is connected with the outlet of the circulating water pump (2); the outlet (1052) of each constant-temperature flow channel (105) is connected with the inlet of the buffer bottle (4); and the outlet of the buffer bottle (4) is connected with the inlet of the circulating water pump (2).

4. The thermostatic fixing device for a gene chip according to claim 1, characterized by: Each constant temperature positioning device (1) comprises a first positioning plate (101) and a second positioning plate (102), a first side of the first positioning plate (101) forms a chip mounting area, and a plurality of accommodation positions (1011) are arranged at equal intervals along the length direction of the chip mounting area, a second side of the first positioning plate (101) is arranged with a flow channel groove (1012) in a meandering manner, and the arrangement area of the flow channel groove (1012) on the second side of each accommodation position (1011) is consistent, a starting end of the flow channel groove (1012) is communicated with the liquid inlet (1051), and a terminal end of the flow channel groove (1012) is communicated with the liquid outlet (1052), the second positioning plate (102) is arranged 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 thermostatic fixing device for gene chip according to claim 4, characterized in that: A plurality of conduction grooves (1013) are further arranged in the flow channel groove (1012), the conduction grooves (1013) are located on the second side of each accommodation position (1011), a plurality of conduction blocks (1021) are arranged on the first side of the second positioning plate (102), the conduction blocks (1021) correspond to the conduction grooves (1013) one by one and are arranged at intervals, and a longitudinal bending part (1053) is formed at the interval between the conduction blocks (1021) and the conduction grooves (1013).

6. The thermostatic fixing device for gene chip according to claim 4, characterized in that: The constant temperature positioning device (1) further comprises a third positioning plate (103), a first side of the third positioning plate (103) is connected with a 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 assembly (6) is fixed in the positioning groove (1031).

7. The thermostatic fixing device for gene chip according to claim 6, characterized in that: The constant temperature positioning device (1) further comprises a heat dissipation mechanism, the heat dissipation mechanism comprises a heat dissipation fan (7) and a heat dissipation plate (104) connected with the third positioning plate (103), a first side of the heat dissipation plate (104) forms a heat dissipation channel (1041), and an inlet of the heat dissipation channel (1041) is communicated with an outlet of the heat dissipation fan (7).

8. The thermostatic fixing device for gene chip according to claim 7, characterized in that: 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, 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), a sealing glue 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), 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), a sealing glue layer is arranged 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 dissipation plate (104) are riveted through screws.

9. A control method for a constant temperature fixing device for a gene chip, characterized by: The constant temperature fixing device for gene chip according to any one of claims 1-8 comprises the following steps: Start the circulating water pump (2) 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); Set a target temperature, and determine a highest allowable temperature and a lowest allowable temperature according to the target temperature; Obtain an initial temperature of the accommodation site, perform first constant temperature control on the medium in the constant temperature flow channel (105) based on the initial temperature of the accommodation site by using the temperature control component (6), and take the target temperature as a constant temperature setting value, which is controlled by the temperature controller (5) to make the temperature of the medium in the constant temperature flow channel (105) gradually approach the constant temperature setting value; Real-time collect the actual temperature of the accommodation site (1011) by the temperature sensor, draw a temperature curve according to the actual temperature, record the first peak value of the temperature curve, and calculate the temperature difference AW of the peak value and the highest allowable temperature; After the first constant temperature control is ended, call the initial temperature of the accommodation site, perform second constant temperature control on the medium in the constant temperature flow channel (105) based on the initial temperature of the accommodation site by using the temperature control component (6), and take the temperature obtained by subtracting AW from the target temperature as the constant temperature setting value; Real-time collect the actual temperature of the accommodation site (1011) by the temperature sensor, draw a temperature curve according to the actual temperature, and when the first peak value of the temperature curve appears, reset the constant temperature setting value to the target temperature, and place the chips one by one on the accommodation site (1011).

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