CN114854570B

CN114854570B - Temperature control device, liquid cooling temperature control system and PCR instrument

Info

Publication number: CN114854570B
Application number: CN202210781924.4A
Authority: CN
Inventors: 朱信; 郭旻; 郭求真; 王梓; 戴涛; 陈衍娟
Original assignee: Rocgene Tecnology Co
Current assignee: Rocgene Tecnology Co
Priority date: 2022-07-05
Filing date: 2022-07-05
Publication date: 2022-09-02
Anticipated expiration: 2042-07-05
Also published as: CN114854570A

Abstract

The embodiment of the disclosure provides a temperature control device, a liquid cooling temperature control system and a PCR instrument. The temperature control device includes: a base plate provided with a coolant flow inlet; the liquid storage cavity is arranged above the bottom plate, and a plurality of first through holes are formed in the top wall; a thermal insulation layer including a plurality of second through holes corresponding to the first through holes; the confluence block is provided with a first side, a second side and a side surface, the confluence block comprises a plurality of third through holes corresponding to the second through holes, a plurality of liquid return holes arranged in pairs with the third through holes, a confluence channel arranged in the confluence block and a cooling liquid outlet arranged on the side surface, each liquid return hole extends into the confluence block from the second side and is communicated with the confluence channel, and the confluence channel is communicated with the cooling liquid outlet; the temperature control plate is arranged on the confluence block and used for providing a heat source; and the heat conducting plate is arranged on the temperature control plate, a plurality of spiral flow channels are arranged on the temperature control plate or the heat conducting plate, the inlet of each spiral flow channel corresponds to the third through hole, and the outlet of each spiral flow channel corresponds to the liquid return hole.

Description

Temperature control device, liquid cooling temperature control system and PCR instrument

Technical Field

Embodiments of the present disclosure relate generally to the field of PCR instruments, and more particularly, to a temperature control device for a PCR instrument, a liquid cooling temperature control system including the temperature control device, and a PCR instrument including the liquid cooling temperature control system.

Background

The Polymerase Chain Reaction (PCR) is a molecular biology technique for amplifying and amplifying specific DNA fragments, and can be regarded as special DNA replication in vitro, and the biggest characteristic of PCR is that trace amount of DNA can be greatly increased. A PCR instrument (also referred to as a gene amplification instrument) is used to perform such reactions.

In a PCR instrument, it is generally necessary to simultaneously amplify a plurality of reaction consumables in parallel. In order to realize parallel gene amplification, a temperature control module is required to control the temperature of a plurality of reaction cups for accommodating reaction consumables. The temperature control module generally includes a heating unit for heating the reaction cup and a cooling unit for cooling the reaction cup. A conventional cooling unit includes a cooling fluid inlet on one side thereof, a cooling fluid outlet on the other side thereof, and a cooling fluid flow passage between the inlet and the outlet. In the coolant flow channel, the temperature of the coolant close to the coolant inlet will be lower, and the temperature of the coolant close to the coolant outlet will be higher due to heat absorption, which can cause each reaction cup to be heated unevenly in the cooling process, thereby affecting the realization of gene amplification.

Disclosure of Invention

The present disclosure is directed to a temperature control device for a PCR instrument, a liquid cooling temperature control system including the temperature control device, and a PCR instrument including the liquid cooling temperature control system, so as to at least partially solve the above problems.

In a first aspect of the present disclosure, there is provided a temperature control device for a PCR instrument, the temperature control device comprising: a base plate having a coolant flow inlet provided therein; a reservoir chamber disposed above the bottom plate for receiving the cooling liquid flowing in through the cooling liquid inlet, a plurality of first through holes for flowing out of the cooling liquid being disposed on a top wall of the reservoir chamber; the heat insulation layer is arranged on the top wall of the liquid storage cavity and comprises a plurality of second through holes corresponding to the first through holes; a manifold block disposed over the insulation layer and having a first side facing the insulation layer, a second side opposite the first side, and a side surface between the first side and the second side, the manifold block including a plurality of third through holes corresponding to the plurality of second through holes, a plurality of liquid return holes disposed in pairs with the plurality of third through holes, each third through hole extending from the first side to the second side, and a liquid coolant outlet disposed on the side surface of the manifold block, each liquid return hole extending from the second side into the manifold block and communicating with the manifold channel, the manifold channel communicating with the liquid coolant outlet; a temperature control plate disposed above the manifold block and configured to provide a heat source; and the heat conducting plate is arranged on the temperature control plate, wherein the temperature control plate or the heat conducting plate is provided with a plurality of spiral flow channels, the flow channel inlet of each spiral flow channel corresponds to the third through hole in the pair of third through holes and the liquid return hole, and the flow channel outlet of each spiral flow channel corresponds to the liquid return hole in the pair of third through holes and the liquid return hole.

In an embodiment according to the present disclosure, the cooling liquid may be uniformly distributed through the plurality of first through holes on the reservoir cavity after entering the reservoir cavity via the cooling liquid flow inlet; subsequently, the cooling liquid flows into the respective spiral flow passages through the respective second through holes and third through holes, and swirls in the spiral flow passages to absorb heat; subsequently, the coolant enters the manifold channel via the corresponding return holes, and then flows out of the manifold block via the coolant flow outlet. Such coolant distribution and flow paths may improve the uniformity of temperature distribution of the thermally conductive plate.

In some embodiments, the plurality of spiral flow channels are disposed on a side of the temperature control plate facing the manifold block, and a side of the temperature control plate facing away from the manifold block is planar.

In some embodiments, the plurality of spiral flow passages are disposed on a side of the heat conductive plate facing the temperature control plate, and additional through holes communicating the plurality of spiral flow passages with the respective third through holes and the liquid return hole are disposed on the temperature control plate.

In some embodiments, a plurality of reaction cups is disposed on a side of the thermally conductive plate opposite the temperature control plate.

In some embodiments, each reaction cup is disposed corresponding to one spiral flow channel of the plurality of spiral flow channels in a thickness direction of the temperature control device.

In some embodiments, the center of each reaction cup is aligned with the center of the corresponding spiral flow channel in the thickness direction.

In some embodiments, a blocking member is provided on a side of the base plate facing the reservoir chamber at a position corresponding to the coolant flow inlet.

In some embodiments, the plurality of first through holes are disposed in rows and columns on the top wall of the reservoir chamber.

In some embodiments, the bus duct includes a first duct extending in a first direction and a second duct extending in a second direction, the first duct communicating with the second duct.

In some embodiments, at least one temperature sensor is disposed on a side of the thermally conductive plate facing the temperature control plate.

In some embodiments, the thermally conductive plate is integrally formed from a single thermally conductive material or is bonded from layers of different thermally conductive materials.

In a second aspect of the present disclosure, there is provided a liquid-cooled temperature control system for a PCR instrument, the liquid-cooled temperature control system comprising: any one of the temperature control devices of the first aspect of the present disclosure; a heat exchanger comprising a supply port and a return port, the return port connected to the coolant flow outlet on the temperature control device; and the circulating pump comprises a liquid inlet and a liquid outlet, the liquid inlet is connected to the liquid supply port of the heat exchanger, and the liquid outlet is connected to the cooling liquid inlet on the temperature control device.

In some embodiments, the heat exchanger comprises: a support; a plurality of heat radiating fins arranged side by side on the bracket and forming an air flow passage between adjacent heat radiating fins; a heat dissipation pipe disposed on the plurality of heat dissipation fins and communicated with the liquid supply port and the liquid return port; and a fan disposed adjacent to the heat sink for flowing the gas in the gas flow passage.

In some embodiments, the circulation pump further comprises a coolant injection port for adding coolant.

In a third aspect of the present disclosure, there is provided a PCR instrument comprising any one of the liquid-cooled temperature control systems of the second aspect of the present disclosure.

It should be understood that what is described in this section is not intended to limit key or critical features of the embodiments of the disclosure, nor is it intended to limit the scope of the disclosure. Other features of the present disclosure will become apparent from the following description.

Drawings

The above and other features, advantages and aspects of embodiments of the present disclosure will become more apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings. In the drawings, like or similar reference characters designate like or similar elements, and wherein:

FIG. 1 shows a schematic structural diagram of a liquid-cooled temperature control system for a PCR instrument according to one embodiment of the present disclosure;

FIG. 2 shows an exploded schematic view of a temperature control device for a PCR instrument according to one embodiment of the present disclosure;

fig. 3A and 3B illustrate a schematic structural diagram of a backplane according to one embodiment of the present disclosure;

FIG. 4 illustrates a schematic structural view of a reservoir chamber according to one embodiment of the present disclosure;

FIG. 5 shows a schematic structural view of an insulation layer according to one embodiment of the present disclosure;

6A-6C illustrate a block diagram according to an embodiment of the present disclosure;

fig. 7A and 7B illustrate a structural schematic view of a temperature control plate according to an embodiment of the present disclosure;

FIG. 7C shows a schematic structural view of a spiral flow channel according to one embodiment of the present disclosure;

fig. 8 shows a schematic structural view of a heat-conducting plate according to one embodiment of the present disclosure;

FIG. 9 shows a graph of maximum temperature, minimum temperature, and average temperature of each reaction cup during a cool down procedure by a temperature control device according to one embodiment of the present disclosure; and

FIG. 10 shows a graph of the maximum temperature difference between individual reaction cups during a cool down procedure of a temperature control device according to one embodiment of the present disclosure.

Detailed Description

Preferred embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While the preferred embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

The term "include" and variations thereof as used herein is meant to be inclusive in an open-ended manner, i.e., "including but not limited to". Unless specifically stated otherwise, the term "or" means "and/or". The term "based on" means "based at least in part on". The terms "one example embodiment" and "one embodiment" mean "at least one example embodiment". The term "another embodiment" means "at least one additional embodiment". The terms "first," "second," and the like may refer to different or the same object.

As described above, in the coolant flow channel of the temperature control module of the conventional PCR instrument, the temperature of the coolant near the coolant inlet will be low, and the temperature of the coolant near the coolant outlet will be high due to heat absorption, which may cause uneven heating of each reaction cup during the temperature reduction process, thereby affecting the gene amplification. The embodiment of the disclosure provides a temperature control device for a PCR instrument, a liquid cooling temperature control system comprising the temperature control device and the PCR instrument comprising the liquid cooling temperature control system, so as to improve the heating uniformity of a reaction cup in the cooling process. Hereinafter, the principle of the present disclosure will be described with reference to fig. 1 to 10.

FIG. 1 shows a schematic structural diagram of a liquid-cooled temperature control system 100 for a PCR instrument according to one embodiment of the present disclosure. As shown in FIG. 1, the fluid-cooled temperature control system 100 described herein generally includes a temperature control device 1, a circulation pump 2, and a heat exchanger 3. The temperature control device 1 is used for adjusting the temperature of a reaction cup (also called a container hole) of a PCR instrument, for example, it can provide a heat source to raise the temperature of the reaction cup, and it can also provide a cooling liquid flow path to lower the temperature of the reaction cup. The coolant required for the temperature control device 1 may be supplied from the heat exchanger 3 by the circulation pump 2, and the coolant heated in the temperature control device 1 is returned to the heat exchanger 3. An exemplary structure of the temperature control device 1 will be described in detail below with reference to fig. 2 to 8.

In some embodiments, as shown in fig. 1, the circulation pump 2 includes a liquid inlet 22 and a liquid outlet 23. The inlet port 22 is connected to the heat exchanger 3 via a circulation line 4 to receive a low temperature (also referred to as cold) cooling liquid from the heat exchanger 3. The liquid outlet 23 is connected to the temperature control device 1 via the circulation line 4 to drive the coolant in a cold state into the temperature control device 1.

As shown in fig. 1, the circulation pump 2 may further include a coolant injection port 21 for adding coolant. When the fluid-cooled temperature control system 100 needs to add or replenish the cooling fluid, an operator can inject the cooling fluid into the circulation pump 2 through the cooling fluid injection port 21.

In some embodiments, as shown in fig. 1, the heat exchanger 3 includes a supply port 301 and a return port 302. The liquid supply port 301 is connected to the liquid inlet port 22 of the circulation pump 2 via the circulation line 4. Under the driving of the circulation pump 2, the cooling liquid in a cold state can flow from the liquid supply port 301 of the heat exchanger 3 into the liquid inlet 22 of the circulation pump 2. The liquid return port 302 of the heat exchanger 3 is connected to the temperature control device 1 via the circulation line 4 to receive the heated and warmed (also referred to as a thermal state) coolant from the temperature control device 1. The coolant in the hot state can be cooled in the heat exchanger 3 and again become in the cold state to be supplied to the circulation pump 2. By such a coolant circulation, the temperature control device 1 can cool the reaction cup.

In some embodiments, as shown in fig. 1, the heat exchanger 3 includes a bracket 31, a plurality of fins 32, a radiating pipe 33, and a fan 35. The fins 32 are arranged side by side on the bracket 31, and airflow passages 34 are formed between adjacent fins 32. The heat radiation pipe 33 is provided on the heat radiation fin 32 and communicates with the liquid supply port 301 and the liquid return port 302. A fan 35 is disposed adjacent to the heat sink 32 for driving the flow of air in the airflow passage 34. When the heat exchanger 3 is operated, the coolant in a hot state from the temperature control device 1 enters the radiating pipe 33 through the liquid return port 302. During the process of the cooling fluid flowing through the radiating pipe 33, the fan 35 may suck the air in the air flow passage 34, so that the air in the air flow passage 34 flows, thereby lowering the temperature of the cooling fluid in the radiating pipe 33 and making the cooling fluid become a cold state. The coolant that has been brought into a cold state flows from the liquid supply port 301 of the heat exchanger 3 into the liquid inlet port 22 of the circulation pump 2. The heat-dissipating efficiency of such a heat exchanger 3 is high and the air flow path 34 does not need to be long, so that the rotation speed or power of the fan 35 can be significantly reduced, thereby reducing noise generated when the entire system is operated.

It should be understood that in other embodiments, the heat exchanger 3 may be of other types or have other configurations, and embodiments of the present disclosure are not limited in this respect.

As described above, the temperature control device 1 can adjust the temperature of the reaction cup by using the heat source and the coolant flow path. An exemplary structure and operation principle of the temperature control device 1 will be described below with reference to fig. 2 to 8. Referring first to FIG. 2, FIG. 2 shows an exploded schematic view of a temperature control device 1 for a PCR instrument according to one embodiment of the present disclosure. As shown in fig. 2, the temperature control apparatus 1 described herein includes a base plate 11, a reservoir chamber 12, a heat insulating layer 13, a manifold block 14, a temperature control plate 15, and a heat conductive plate 16, which are sequentially arranged from bottom to top in a thickness direction H thereof. That is, the liquid storage chamber 12 is disposed on the bottom plate 11, the heat insulating layer 13 is disposed on the liquid storage chamber 12, the bus block 14 is disposed on the heat insulating layer 13, the temperature control plate 15 is disposed on the bus block 14, and the heat conducting plate 16 is disposed on the temperature control plate 15. The adjacent parts of the temperature control device 1 are hermetically connected, i.e. the cooling liquid flowing in the temperature control device 1 will not flow out from between the adjacent parts of the temperature control device 1.

As shown in FIG. 2, a plurality of reaction cups 17 are disposed on the side of the heat conducting plate 16 opposite to the temperature control plate 15, and the reaction cups 17 are used for accommodating reaction consumables of the PCR instrument. During the operation of the PCR apparatus, the temperature of each reaction cup 17 can be adjusted by the temperature control device 1, for example, the temperature of the reaction cup 17 can be increased or decreased by cooling. In order to heat the reaction cup 17, a heat source, such as a heating wire or other type of heat source, may be disposed in the temperature control plate 15. When the heat source is operated, the heat source in the temperature-controlled plate 15 generates heat, thereby heating the reaction cup 17 via the heat-conducting plate 16. In order to cool down the reaction cup 17, a cooling liquid channel may be provided in the temperature control device 1. The coolant flow passage is formed by the respective components of the temperature control device 1, which will be described in detail below with reference to fig. 3A to 8.

In some embodiments, the various parts of the temperature control device 1 may be joined together by welding or adhesive bonding. In other embodiments, the various parts of the temperature control device 1 may be bolted together. In other embodiments, the various parts of the temperature control device 1 may be connected together in other manners, and the embodiments of the present disclosure are not limited thereto.

An exemplary structure of each part of the temperature control device 1 will be described below with reference to fig. 3A to 8.

FIGS. 3A and 3B illustrate a schematic structural view of the base plate 11 according to one embodiment of the present disclosure, wherein FIG. 3A illustrates a first side of the base plate 11, corresponding to the bottom side of the base plate 11 illustrated in FIG. 2, i.e., the side facing away from the reservoir 12; fig. 3B shows a second side of the base plate 11, corresponding to the top side of the base plate 11 shown in fig. 2, i.e., the side facing the reservoir 12.

As shown in fig. 3A, the base plate 11 is provided with a coolant flow inlet 113 on a first side thereof. The coolant flow inlet 113 may be connected to the outlet 23 of the circulation pump 2 via the circulation line 4 shown in fig. 1. With this arrangement, the coolant from the circulation pump 2 can enter the temperature control device 1 via the coolant flow inlet 113. In some embodiments, as shown in FIG. 3A, the coolant flow inlet 113 may be disposed in the middle of the first side of the base plate 11. It should be understood that other locations for the coolant flow inlet 113 to be disposed on the first side of the base plate 11 are possible and embodiments of the present disclosure are not limited in this regard.

In some embodiments, as shown in fig. 3B, a barrier 114 is provided on the second side of the base plate 11 at a location corresponding to the coolant flow inlet 113. For example, in the case where the coolant flow inlet 113 is provided at the middle of the first side of the base plate 11, the barrier 114 is provided at the middle of the second side of the base plate 11. Whereas in case the coolant flow inlet 113 is provided at another location on the first side of the base plate 11, the barriers 114 are provided at corresponding locations on the second side of the base plate 11. By providing the blocking member 114 at a position corresponding to the coolant flow inlet 113, when the coolant flows into the reservoir chamber 12 through the coolant flow inlet 113, the coolant will impinge on the blocking member 114 to change the flow direction, so that the coolant will uniformly fill the reservoir chamber 12 in a flood-like manner. Furthermore, the flow rate of each exit hole can be maintained uniform as the cooling fluid exits from above reservoir 12, as will be further described below in connection with FIG. 4.

In one embodiment, the stop 114 may be a baffle plate bolted to the second side of the base plate 11. In other embodiments, the stop 114 may be another form of stop or otherwise secured to the second side of the base plate 11, and embodiments of the present disclosure are not limited in this respect.

FIG. 4 shows a schematic diagram of a reservoir chamber 12 according to one embodiment of the present disclosure. In order to more clearly show the structure of the reservoir 12, fig. 4 shows the reservoir 12 shown in fig. 2 after being turned upside down. That is, FIG. 4 shows the bottom side of the reservoir 12, while FIG. 2 shows the top side of the reservoir 12. As shown in fig. 4, reservoir 12 includes a top wall 122 and a side wall 121 surrounding top wall 122. One side of the side wall 121 is connected to the top wall 122. The other side of the sidewall 121 has an open end 120, and the open end 120 is for connection to the bottom plate 11. With such an arrangement, the reservoir chamber 12 may form, together with the bottom plate 11, an inner space for receiving the coolant flowing in via the coolant flow inlet 113.

As shown in fig. 4, the top wall 122 of the reservoir chamber 12 is provided with a plurality of first through holes 123 through which the cooling liquid flows out. When the circulation pump 2 is operated, the coolant in the reservoir 12 may uniformly flow out of the reservoir 12 through the first through-hole 123. In some embodiments, as shown in fig. 4, the first through-holes 123 are uniformly arranged in rows and columns on the top wall 122 of the reservoir chamber 12. It should be understood that the first through hole 123 may be disposed on the top wall 122 of the liquid storage chamber 12 in other forms, which may be determined according to the number and the disposition positions of the reaction cups 17 on the heat conducting plate 16, and the embodiment of the present disclosure is not limited thereto.

Fig. 5 shows a schematic structural view of an insulation layer 13 according to one embodiment of the present disclosure. As shown in fig. 5, the thermal insulation layer 13 includes a plurality of second through holes 131 corresponding to the plurality of first through holes 123. Referring to fig. 4 and 5, each of the second through holes 131 is aligned with one of the first through holes 123 of the reservoir chamber 12 so that the cooling liquid flowing out of the first through hole 123 can flow through the second through hole 131. The heat insulating layer 13 can prevent heat of the coolant in the heat state in the manifold block 14 and heat generated by the heat source in the temperature control plate 15 from being transferred to the reservoir 12, so as not to affect the cooling effect of the coolant in the reservoir 12.

Fig. 6A-6C illustrate a schematic structural view of the manifold block 14 according to one embodiment of the present disclosure, wherein fig. 6A illustrates a first side of the manifold block 14, corresponding to the bottom side of the manifold block 14 shown in fig. 2, i.e., the side facing the insulation layer 13; fig. 6B shows a second side of the manifold block 14, corresponding to the top side of the manifold block 14 shown in fig. 2, i.e. the side facing the temperature control plate 15; fig. 6C shows a partial cross-sectional view of the second side of the manifold block 14.

As shown in fig. 6A to 6C, the manifold block 14 includes a plurality of third through holes 143. Each third through hole 143 extends from the first side to the second side of the bus block 14. The third through hole 143 is provided corresponding to the second through hole 131 in the thermal insulation layer 13. Each third through hole 143 is aligned with a respective second through hole 131 on the insulation layer 13 at the first side of the bus bar 14, so that the cooling liquid from the second through hole 131 can flow through the respective third through hole 143.

As shown in fig. 6B and 6C, the manifold block 14 further includes a plurality of liquid return holes 144 provided in pairs with the third through holes 143. Each fluid return bore 144 extends from the second side of the manifold block 14 to the interior of the manifold block 14. Each pair of third through holes 143 and liquid return holes 144 is represented by a dashed box 145. The manifold block 14 also includes a manifold channel 147 disposed inside the manifold block 14 and a coolant flow outlet 146 disposed on the side surface 140 of the manifold block 14. Each return bore 144 communicates with a converging flow passage 147, and the converging flow passage 147 communicates with a coolant flow outlet 146. The coolant flow outlet 146 may be connected to the liquid return port 302 of the heat exchanger 3 via the circulation line 4 shown in fig. 1. With this arrangement, the coolant in the hot state can flow into the confluence passage 147 via the liquid return hole 144 and then flow out of the temperature control device 1 from the coolant flow outlet 146 to be returned to the heat exchanger 3 via the liquid return port 302 of the heat exchanger 3 for the next cooling cycle.

In one embodiment, as shown in fig. 6C, the bus duct 147 includes a first duct 1471 extending in a first direction and a second duct 1472 extending in a second direction. The first passage 1471 communicates with the second passage 1472 and is connected to the coolant flow outlet 146. The first direction and the second direction may be orthogonal or oblique to each other. In other embodiments, the bus passage 147 may have other arrangements, as embodiments of the present disclosure are not limited in this respect.

In one embodiment, as shown in fig. 6A to 6C, a plurality of coolant flow outlets 146, for example, six, may be provided on the side surface 140 of the junction block 14, and each coolant flow outlet 146 may be connected to the liquid return port 302 of the heat exchanger 3 via the circulation line 4 shown in fig. 1. In other embodiments, more or fewer coolant flow outlets 146 may be provided on the side surface 140 of the manifold block 14, as embodiments of the present disclosure are not limited in this regard.

Fig. 7A and 7B show schematic structural views of a temperature control plate 15 according to one embodiment of the present disclosure, wherein fig. 7A shows a first side of the temperature control plate 15, corresponding to the bottom side of the temperature control plate 15 shown in fig. 2, i.e. the side facing the manifold block 14; fig. 7B shows a second side of the temperature-control plate 15, corresponding to the top side of the temperature-control plate 15 shown in fig. 2, i.e. the side facing the heat-conducting plate 16. As shown in FIG. 7A, a plurality of spiral channels 153, which may also be referred to as spiral channels, are disposed on the first side of the temperature control plate 15. Fig. 7C shows an exemplary structure of the spiral flow passage 153. As shown in fig. 7C, each spiral channel 153 includes a channel inlet 1531 and a channel outlet 1532. The flow channel inlet 1531 of each spiral flow channel 153 corresponds to the third through hole 143 of the pair of third through holes 143 and the liquid return hole 144. The flow channel outlet 1532 of each spiral flow channel 153 corresponds to the liquid return hole 144 of the pair of third through holes 143 and the liquid return hole 144.

Referring to fig. 6A to 7C, the third through hole 143 of the pair of third through holes 143 and the third through hole 143 of the liquid return hole 144 of the manifold block 14 are connected to the flow channel inlet 1531 of the corresponding spiral flow channel 153, and the liquid return hole 144 of the pair of third through holes 143 and the liquid return hole 144 of the manifold block 14 is connected to the flow channel outlet 1532 of the corresponding spiral flow channel 153.

In some embodiments, as shown in FIG. 7C, the channel inlet 1531 is located in the middle of the spiral channel 153 and the channel outlet 1532 is located at the periphery of the spiral channel 153. In other embodiments, flow channel outlet 1532 can be located in the middle of spiral flow channel 153, and flow channel inlet 1531 can be located at the periphery of spiral flow channel 153.

In some embodiments, as shown in fig. 7B, the second side of the temperature control plate 15 is planar. In other embodiments, the second side of the temperature control plate 15 may have other structural forms, and the embodiments of the disclosure are not limited thereto.

As described above, in order to heat and raise the temperature of the reaction cup 17, a heat source, such as a heating wire or other type of heat source, may be disposed in the temperature control plate 15. The heat source in the temperature control plate 15 may be arranged on the second side of the temperature control plate 15 or inside the temperature control plate 15. When the heat source is operated, the heat source will generate heat, thereby heating the reaction cup 17 via the heat conducting plate 16.

Fig. 8 shows a schematic structural view of the heat-conducting plate 16 according to one embodiment of the present disclosure. As shown in fig. 8, the heat-conducting plate 16 has a first side and a second side opposite to each other. The first side of the thermally conductive plate 16 corresponds to the bottom side of the thermally conductive plate 16 shown in fig. 2. The second side of the thermally conductive plate 16 corresponds to the top side of the thermally conductive plate 16 shown in fig. 2. The reaction cup 17 is disposed on the second side of the heat conductive plate 16. The first side of the heat conducting plate 16 is used for contacting the temperature control plate 15, so as to transfer the heat generated by the temperature control plate 15 to the reaction cup 17 when the reaction cup 17 is heated and the heat of the reaction cup 17 is transferred to the cooling liquid in the temperature control plate 15 when the reaction cup 17 is cooled and cooled.

In some embodiments, as shown in fig. 8, one or more temperature sensors 163 are disposed on a first side of the thermally conductive plate 16. With the temperature sensor 163, the temperature of the heat-conducting plate 16 can be monitored in real time.

In some embodiments, the thermally conductive plate 16 is integrally formed from a single thermally conductive material, such as a metallic material. In other embodiments, the heat-conducting plate 16 may be made of layers of different heat-conducting materials, which are not limited by the embodiments of the present disclosure.

In some embodiments, referring to fig. 2, 7A and 8, each reaction cup 17 is disposed corresponding to one spiral flow channel 153 of the plurality of spiral flow channels 153 in the thickness direction H of the temperature control device 1. In other words, one spiral flow channel 153 is provided for each reaction cup 17 to cool the reaction cup 17.

In some embodiments, the center of each reaction cup 17 is aligned with the center of the corresponding spiral flow channel 153 in the thickness direction H of the temperature control device 1. In other embodiments, the center of each reaction cup 17 and the center of the corresponding spiral flow channel 153 may be offset from each other in the thickness direction H, and the embodiments of the present disclosure are not limited thereto.

An exemplary operation flow of the temperature control device 1 will be described below with reference to fig. 1 to 8.

When the reaction cup 17 needs to be heated and heated, the heat source in the temperature control plate 15 generates heat and transfers the heat to the reaction cup 17 through the heat conduction plate 16. In this process, the circulation pump 2 and the heat exchanger 3 are not operated, so that the coolant in the temperature control device 1 is in a stationary state. When the temperature sensor 163 detects that the temperature of the heat conductive plate 16 rises to a predetermined temperature value, the heat source in the temperature control plate 15 may stop heating.

When the reaction cup 17 needs to be cooled, the circulating pump 2 and the heat exchanger 3 start to work, and the cooling liquid is driven to flow in the liquid cooling and temperature control system 100. The cooling liquid after heat dissipation and temperature reduction by the heat exchanger 3 is driven by the circulating pump 2 to flow in a single direction in the circulating pipeline 4, and enters the liquid storage cavity 12 through the cooling liquid inlet 113. After the cooling fluid enters reservoir 12, barrier member 114 changes the direction of flow of the cooling fluid, causing the cooling fluid to smoothly fill the entire interior space within reservoir 12 without splashing. Subsequently, the cooling fluid may flow out of the reservoir 12 via the first through-holes 123 of the reservoir 12, wherein the flow rate of the cooling fluid in each of the first through-holes 123 may be substantially uniform. Subsequently, the coolant is injected into the spiral flow channel 153 on the first side of the temperature control plate 15 through the second through-holes 131 in the thermal insulation layer 13 and the third through-holes 143 in the manifold block 14. At this time, the heat conductive plate 16 may transfer the heat of the reaction cup 17 to the coolant in the spiral flow passage 153, so that the coolant becomes in a hot state. Subsequently, the coolant that has been changed to the hot state flows from the spiral flow passage 153 into the liquid return hole 144 in the junction block 14, is injected into the junction channel 147 inside the junction block 14, and then flows out of the temperature control device 1 via the coolant flow outlet 146. The coolant flowing out of the coolant outlet 146 is returned to the heat exchanger 3 via the circulation line 4 to be cooled, and thus the next cooling cycle is performed.

The cooling liquid circulates through the liquid-cooled temperature control system 100, which lowers the temperature of the heat conducting plate 16, thereby lowering the temperature of the reaction cup 17. By controlling the flow rate of the coolant using the circulation pump 2, the temperature decrease rate of the reaction cup 17 can be controlled. The temperature signal monitored by the temperature sensor 163 can be fed back to the control system to control the flow rate of the cooling liquid, so that the steady-state temperature of the reaction cup 17 can be flexibly adjusted.

In some embodiments, the flow rate of the cooling liquid in each first through hole 123 can be adjusted, so that the cooling rate in each spiral flow channel 153 can be independently controlled, thereby improving the temperature uniformity of the whole heat conducting plate 16, or the temperature of the reaction cup 17 is in a set gradient distribution.

In an embodiment according to the present disclosure, the cooling liquid may be uniformly distributed through the plurality of first through holes 123 on the reservoir chamber 12 after entering the reservoir chamber 12 via the cooling liquid inlet 113; subsequently, the cooling liquid flows into the respective spiral flow passages 153 through the respective second and third through

holes

131 and 143, and swirls in the spiral flow passages 153 to absorb heat; the coolant then enters the manifold channel 147 via the respective return holes 144, and then exits the manifold block 14 via the coolant flow outlet 146. Such coolant distribution and flow paths can improve the temperature distribution uniformity of the heat conducting plate 16, so that each reaction cup 17 is heated uniformly in the cooling process, thereby facilitating the realization of gene amplification.

Fig. 9 shows a graph of the maximum temperature, the minimum temperature, and the average temperature of each reaction cup 17 during the temperature reduction process of the temperature control device 1 according to one embodiment of the present disclosure, and fig. 10 shows a graph of the maximum temperature difference between each reaction cup 17 during the temperature reduction process of the temperature control device 1 according to one embodiment of the present disclosure. FIGS. 9 and 10 show the temperature change of each cuvette 17 within 15 seconds after the temperature of the cuvette has been lowered to 95 ℃ and the coolant starts to flow. As shown in fig. 9 and 10, the maximum temperature difference between the respective reaction cups 17 during the cooling process is about 12.8 ℃, and the temperature difference increases and then decreases with time, with fluctuation in the middle. Therefore, in the temperature reduction process of the temperature control device 1, the temperature difference among the reaction cups 17 is very small, and the temperature distribution uniformity is good.

In some embodiments, instead of providing the spiral flow channels 153 on the temperature control plate 15, a plurality of spiral flow channels 153 may be provided on the side of the heat conductive plate 16 facing the temperature control plate 15, and additional through holes communicating the plurality of spiral flow channels 153 with the respective third through holes 143 and the liquid return holes 144 are provided on the temperature control plate 15. With this arrangement, the coolant from the third through-hole 143 in the junction block 14 can flow into the spiral flow passage 153 in the heat conductive plate 16 via the additional through-hole in the temperature control plate 15. At this time, the heat conductive plate 16 may transfer the heat of the reaction cup 17 to the coolant in the spiral flow passage 153, so that the coolant becomes in a hot state. Subsequently, the coolant that has been changed to the hot state flows from the spiral flow channel 153 into the liquid return hole 144 in the junction block 14 via the additional through hole, is injected into the junction channel 147 inside the junction block 14, and then flows out of the temperature control device 1 via the coolant flow outlet 146.

The liquid-cooled temperature control system 100 according to the embodiment of the present disclosure may be applied to various PCR instruments in order to control the temperature of reaction consumables when performing gene amplification. It should be understood that the liquid-cooled temperature control system 100 according to the embodiments of the present disclosure may also be applied to temperature control of other biochemical reactions, and the embodiments of the present disclosure are not limited thereto.

Having described embodiments of the present disclosure, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen in order to best explain the principles of the embodiments, the practical application, or improvements made to the technology in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A temperature control device (1) for a PCR instrument, the temperature control device (1) comprising:

a base plate (11) provided with a coolant flow inlet (113);

a reservoir chamber (12) disposed above the bottom plate (11) for receiving the cooling liquid flowing in through the cooling liquid inlet (113), wherein a plurality of first through holes (123) for the cooling liquid to flow out are disposed on a top wall (122) of the reservoir chamber (12);

a thermal insulation layer (13) disposed on the top wall (122) of the reservoir chamber (12) and including a plurality of second through holes (131) corresponding to the plurality of first through holes (123);

a manifold block (14) disposed over the insulation layer (13) and having a first side facing the insulation layer (13), a second side opposite the first side, and a side surface (140) between the first side and the second side, the manifold block (14) including a plurality of third through holes (143) corresponding to the plurality of second through holes (131), a plurality of liquid return holes (144) disposed in pairs with the plurality of third through holes (143), a manifold channel (147) disposed inside the manifold block (14), and a coolant flow outlet (146) disposed on the side surface (140) of the manifold block (14), each third through hole (143) extending from the first side to the second side, each liquid return hole (144) extending from the second side to inside the manifold block (14) and communicating with the manifold channel (147), the converging channel (147) communicates with the coolant flow outlet (146);

a temperature control plate (15) disposed above the junction block (14) and configured to provide a heat source; and

and the heat conduction plate (16) is arranged on the temperature control plate (15), a plurality of spiral flow channels (153) are arranged on the temperature control plate (15) or the heat conduction plate (16), a flow channel inlet (1531) of each spiral flow channel (153) corresponds to the third through hole (143) in the pair of third through holes (143) and the liquid return hole (144), and a flow channel outlet (1532) of each spiral flow channel (153) corresponds to the liquid return hole (144) in the pair of third through holes (143) and the liquid return hole (144).

2. The temperature control device (1) according to claim 1, characterized in that the plurality of spiral flow channels (153) are arranged on a side of the temperature control plate (15) facing the manifold block (14) and a side of the temperature control plate (15) facing away from the manifold block (14) is planar.

3. The temperature control device (1) according to claim 1, wherein the plurality of spiral flow channels (153) are provided on a side of the heat conductive plate (16) facing the temperature control plate (15), and additional through holes communicating the plurality of spiral flow channels (153) with the respective third through holes (143) and the liquid return hole (144) are provided on the temperature control plate (15).

4. Temperature control device (1) according to claim 1, characterized in that a plurality of reaction cups (17) is arranged on the side of the thermally conductive plate (16) opposite to the temperature control plate (15).

5. The temperature control device (1) according to claim 4, wherein each reaction cup (17) is provided in correspondence with one spiral flow channel (153) of the plurality of spiral flow channels (153) in a thickness direction (H) of the temperature control device (1).

6. Temperature control device (1) according to claim 5, characterized in that the center of each reaction cup (17) is aligned with the center of the corresponding spiral flow channel (153) in the thickness direction (H).

7. Temperature control device (1) according to claim 1, characterized in that a blocking member (114) is provided on a side of the base plate (11) facing the reservoir chamber (12) at a position corresponding to the coolant flow inlet (113).

8. Temperature control device (1) according to claim 1, characterized in that the plurality of first through holes (123) are arranged in rows and columns on the top wall (122) of the reservoir chamber (12).

9. The temperature control device (1) according to claim 1, wherein the confluence passage (147) includes a first passage (1471) extending in a first direction and a second passage (1472) extending in a second direction, the first passage (1471) communicating with the second passage (1472), the first direction and the second direction being orthogonal or oblique to each other.

10. Temperature control device (1) according to claim 1, characterized in that at least one temperature sensor (163) is arranged on a side of the thermally conductive plate (16) facing the temperature control plate (15).

11. Temperature control device (1) according to claim 1, characterized in that the heat-conducting plate (16) is integrally formed from a single heat-conducting material or is bonded from layers of different heat-conducting materials.

12. A liquid cooled temperature control system (100) for a PCR instrument, the liquid cooled temperature control system (100) comprising:

the temperature control device (1) according to any one of claims 1 to 11;

a heat exchanger (3), the heat exchanger (3) comprising a liquid supply port (301) and a liquid return port (302), the liquid return port (302) being connected to the coolant flow outlet (146) on the temperature control device (1); and

circulating pump (2), including inlet (22) and liquid outlet (23), inlet (22) are connected to liquid supply mouth (301) of heat exchanger (3), liquid outlet (23) are connected to on temperature control device (1) coolant liquid inlet (113).

13. The liquid cooled temperature control system (100) of claim 12, wherein the heat exchanger (3) comprises:

a bracket (31);

a plurality of fins (32) arranged side by side on the bracket (31) and forming airflow passages (34) between adjacent fins (32);

a heat radiation pipe (33) provided on the plurality of heat radiation fins (32) and communicated with the liquid supply port (301) and the liquid return port (302); and

a fan (35) disposed adjacent to the heat sink (32) for flowing the gas in the gas flow passage (34).

14. The liquid-cooled temperature control system (100) of claim 12, wherein the circulation pump (2) further comprises a coolant inlet port (21) for adding coolant.

15. A PCR instrument comprising a liquid cooled temperature control system (100) according to any of claims 12 to 14.