CN218579970U

CN218579970U - Thermal cycling device

Info

Publication number: CN218579970U
Application number: CN202220930153.6U
Authority: CN
Inventors: 邱勇; 阳方义; 陈华贵
Original assignee: Rwd Life Science Co ltd
Current assignee: Rwd Life Science Co ltd
Priority date: 2022-04-21
Filing date: 2022-04-21
Publication date: 2023-03-07
Anticipated expiration: 2032-04-21

Abstract

An embodiment of the utility model provides a thermal cycle device, include: a sample block (1) provided with a blind hole array; n heating and cooling devices (2) arranged below the sample block (1), wherein N is a positive integer greater than or equal to 1; and a heat sink (3) disposed below the N heating and cooling devices (2); an indium-based metal sheet (3000) is arranged between the sample block (1) and the N heating and cooling devices (2), and an indium-based metal sheet (3000) is arranged between the N heating and cooling devices (2) and the heat dissipation groove (3). The embodiment of the utility model provides a between sample piece and heating and cooling device, improve heat conduction efficiency through indium base sheetmetal between heating and cooling device and the radiating groove, improved thermal cycle device's manufacturability, improved thermal cycle device heat conduction efficiency's homogeneity and uniformity, guaranteed the accuracy and the efficiency of PCR experiment.

Description

Heat circulation device

Technical Field

The utility model relates to a carry out chemical reaction or biological reaction's reaction vessel technical field, especially relate to a thermal cycle device.

Background

In exploring optimal reaction temperatures and optimal reaction times for biological or chemical samples, it is often necessary to set and perform a series of temperature cycles on the biological or chemical sample from which an optimal temperature and time combination is selected.

The prior art device for performing the series of temperature cycles is a Polymerase Chain Reaction (PCR) nucleic acid amplification instrument, which can be also called a PCR instrument or a thermal cycling device. The thermal circulation device comprises a sample block on which a blind hole array is uniformly arranged, a plurality of heating and cooling devices are arranged below the sample block, and heat dissipation grooves are arranged below the plurality of heating and cooling devices. And placing the PCR plate or the PCR tube filled with the biological sample into the blind hole of the sample block, and enabling the biological sample to undergo a plurality of temperature cycles in the thermal cycling device by presetting heating temperature, heating time, cooling temperature and cooling time. When the sample block is heated, the plurality of heating and cooling devices are heated to the same or different preset temperatures to heat the corresponding sample block area, and the heat is conducted to the biological sample through the blind holes of the sample block and the PCR plate. When the sample block is cooled, the plurality of heating and cooling devices cool the sample block area corresponding to the sample block, and redundant heat is dissipated through the heat dissipation groove.

In the heating and cooling process, heat conduction efficiency is improved by smearing heat-conducting silicone grease between the sample block and the heating and cooling device and between the heating and cooling device and the heat dissipation groove. However, in the production process, the uniformity and consistency of the heat-conducting silicone grease coating are difficult to guarantee, so that the accuracy and efficiency of the PCR experiment are influenced.

SUMMERY OF THE UTILITY MODEL

An embodiment of the utility model provides a thermal cycle device aims at solving scribbling of heat conduction silicone grease among the prior art and influences the accuracy and the problem of efficiency of PCR experiment.

In a first aspect, a thermal cycler is provided, comprising:

a sample block (1) provided with a blind hole array;

n heating and cooling devices (2) arranged below the sample block (1), wherein N is a positive integer greater than or equal to 1; and

the heat dissipation grooves (3) are arranged below the N heating and cooling devices (2);

wherein, be provided with indium base sheetmetal (3000) between sample piece (1) and N heating and cooling device (2), be provided with indium base sheetmetal (3000) between N heating and cooling device (2) and radiating groove (3).

The embodiment of the utility model provides a improve heat-conduction efficiency through indium base sheetmetal between sample piece and heating and cooling device, between heating and cooling device and the radiating groove, improved thermal cycle device's manufacturability, improved thermal cycle device heat-conduction efficiency's homogeneity and uniformity, guaranteed the accuracy and the efficiency of PCR experiment.

Drawings

The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:

fig. 1 is an exploded view of a thermal cycler according to an embodiment of the present invention;

fig. 2 is a schematic view of a thermal cycle apparatus provided by an embodiment of the present invention;

fig. 3 is another exploded view of a thermal cycler according to an embodiment of the present invention.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar modules or modules having the same or similar functionality throughout. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present invention, and should not be construed as limiting the present invention. On the contrary, the embodiments of the invention include all changes, modifications and equivalents coming within the spirit and terms of the claims appended hereto.

The embodiment of the utility model provides a between sample piece and heating and cooling device, improve heat conduction efficiency through indium base sheetmetal between heating and cooling device and the radiating groove, improved thermal cycle device's manufacturability, improved thermal cycle device heat conduction efficiency's homogeneity and uniformity, guaranteed the accuracy and the efficiency of PCR experiment.

Fig. 1 is an exploded view of a thermal cycler according to an embodiment of the present invention. Fig. 2 is a schematic view of a thermal cycler according to an embodiment of the present invention. As shown in fig. 1 and 2, the thermal cycler includes a sample block 1, N heating and cooling devices 2, and a heat sink 3.

In the embodiment of the utility model provides an in, be provided with the blind hole of even equidistant range on the sample piece 1, form the blind hole array. The blind holes refer to the hole grooves on the sample block 1 for placing the PCR tubes, and the size and the distance of the blind holes are set to be matched with standard or non-standard PCR plates and PCR tubes, so that the PCR plate 1000 containing biological samples can be integrally placed in the blind hole array, and the inner walls of the blind holes are close to the outer walls of the tubes of the PCR plate 1000 as much as possible, thereby being beneficial to heat conduction. The biological sample is a substance to undergo a thermal cycling reaction, and includes, but is not limited to, oligonucleotides as primers, dNTP mixture, taq DNA polymerase, PCR buffer, and the like. The sample block 1 as a whole may be made of a material having good heat conductivity. Preferably, it is an aluminum alloy, aluminum, copper, silver, or the like.

N heating and cooling devices 2 are arranged below the sample block 1, and N is a positive integer greater than or equal to 1. As shown in fig. 1, N is six, but is not limited thereto. The heating and cooling device 2 includes, but is not limited to, TEC (semiconductor Cooler), heater wire, heater rod, air conduction device or liquid conduction device, etc. In an embodiment of the present invention, the six TECs independently heat and/or cool the bottoms of the blind holes located in six different regions of the sample block 1 to a target temperature, each region comprising one or more blind holes, respectively. In this case, the sample block 1 is divided into different regions in the shape of the TEC. The blind hole corresponding to each TEC is a heating and/or cooling area thereof. By the mode, different heating temperatures, different heating times and different heating rates can be set for different areas of the sample block 1, the volume of the biological sample in the PCR tube can be changed according to the division of the different areas of the sample block 1, the primers in the PCR tube can be changed, and the optimal conditions for carrying out experiments can be explored.

The heat dissipation groove 3 is disposed below the N heating and cooling devices 2, and is used to dissipate excess heat. The heat sink 3 is provided near one side of the N heating and cooling devices 2, and a PCB board 2000 may be disposed around the N heating and cooling devices 2 as a driving circuit of the N heating and cooling devices 2 and a driving circuit of a heat sensitive sensor (not shown). One side of the heat dissipation groove 3, which is far away from the N heating and cooling devices 2, is provided with a plurality of heat dissipation fins, so that the contact area of the heat dissipation groove 3 and air is increased, and the heat dissipation efficiency is improved. The cross section of the heat dissipation fin is rectangular or triangular, which is not limited herein.

An indium-based metal sheet 3000 is disposed between the sample block 1 and the N heating and cooling devices 2, and an indium-based metal sheet 3000 is disposed between the N heating and cooling devices 2 and the heat sink 3 to improve heat conduction efficiency. Indium-based metal sheets are often used for heat dissipation of semiconductor chips, are also widely used as gaskets or lining layers in high-altitude instruments and aerospace equipment, and are good heat-conducting materials. In addition, indium-based metal sheets are also commonly used as ultrasonic linear retardation contactors and the like.

During installation, the indium-based metal sheet 3000 is flatly placed between the sample block 1 and the heating and cooling device 2 and between the heating and cooling device 2 and the heat dissipation groove 3, each indium-based metal sheet 3000 is fastened and pressed through a screw, the installation process is simple, and the installation consistency of each time between the indium-based metal sheets are guaranteed.

As an embodiment of the present invention, N smaller indium-based metal pieces 3000 are disposed between the sample block 1 and the N heating and cooling devices 2, and N smaller indium-based metal pieces 3000 are disposed between the N heating and cooling devices 2 and the heat sink 3, corresponding to the N heating and cooling devices 2. As another embodiment of the present invention, a larger indium-based metal sheet 3000 is disposed between the sample block 1 and the N heating and cooling devices 2, and a larger indium-based metal sheet 3000 is disposed between the N heating and cooling devices 2 and the heat dissipating grooves 3.

Fig. 3 is another exploded view of a thermal cycler according to an embodiment of the present invention. As shown in fig. 3, the thermal cycler includes a sample block 1, N TECs, a heat sink 3, a spacer 4, a holding-down member 5, and an indium-based metal plate 3000.

A single indium-based metal sheet 3000 is flatly placed on the plane of the upper part of the heat sink 3, and the lower surface of the indium-based metal sheet 3000 contacts the upper surface of the heat sink 3. In other embodiments, the N smaller pieces of indium-based metal 3000 may be placed flat on the upper surface of the heat sink 3. The N TECs are placed on the indium-based metal plate 3000, respectively, and the lower surfaces of the TECs are in contact with the upper surface of the indium-based metal plate 3000. The isolating piece 4 is filled between the N TECs, and the isolating piece 4 is a high-temperature-resistant heat-insulating material, so that the TECs are mutually thermally isolated. The N smaller indium-based metal sheets 3000 are respectively and correspondingly placed on the N TECs, and the lower surfaces of the N indium-based metal sheets 3000 are in contact with the upper surfaces of the TECs. The sample block 1 is placed on the N indium-based metal sheets 3000, and the bottom of each blind hole is in contact with the upper surface of the indium-based metal sheet 3000. The pressing piece 5 presses the edge position of the sample block 1, the pressing piece 5 is connected to the heat dissipation groove 3 through screws, the sample block 1 and the N TECs are pressed tightly, and the sample block 1, the TECs and the indium-based metal sheet 3000 are further pressed tightly on the heat dissipation groove 3.

The thermal cycler can be used in a variety of embodiments for controlling the temperature of the bottom of blind holes in different areas of the block 1. As an embodiment of the utility model, the PCR pipe that holds in all blind holes of sample block 1 reacts according to the same temperature, and N TEC heats or refrigerates according to same temperature instruction to the temperature that reaches all blind holes is unanimous. As another embodiment of the utility model, the PCR pipe that holds in the blind hole of 1 different regions of sample piece reacts according to the temperature of difference, realizes that the temperature of the blind hole of 1 different regions of sample piece is gradient change at same thermal cycle in-process. As another embodiment of the present invention, some blind holes are selected from different regions of the sample block 1 to accommodate PCR tubes and react at different temperatures. The larger the distance between the selected blind holes is, the better the distance between the selected blind holes is, the adjacent blind holes can be subjected to temperature compensation (heating or cooling) by adopting the TEC, and the purpose of reducing the thermal influence between the selected adjacent blind holes 11 is achieved.

The heat circulation device also comprises a heating and cooling control system, a central control system and a heat dissipation control system. In the embodiment of the present invention, different high-sensitivity thermal sensors (not shown in the figure) are respectively connected to different regions of the sample block 1.

During heating, the central control system sends out a sample block heating command, and the command is transmitted to the heating and cooling control system through the central and heating and cooling control loops. And after the heating and cooling control system is processed, the heating and cooling control system acts on the N TECs through the TEC control loop, the upper surfaces of the TECs start to heat, and the lower surfaces of the TECs start to refrigerate correspondingly. The temperature sensor transmits the detected temperature back to the heating and cooling control system through the TEC control loop, the heating and cooling control system judges whether the target temperature is reached, and then the TEC is controlled by the TEC control loop to continue heating or stop heating. To continue heating, the TEC continuously conducts heat to the sample block 1, thereby continuously providing heat to the PCR plate or the biological sample within the PCR tube. This process requires several cycles.

When cooling is carried out, the central control system sends out a sample block cooling instruction, and the instruction is transmitted to the heating and cooling control system through the central and heating and cooling control loop and is transmitted to the heat dissipation control system through the central and heat dissipation control loop. The heating and cooling control system is processed and then acts on the N TECs through the TEC control loop, the upper surfaces of the TECs start to refrigerate, and the lower surfaces of the TECs correspondingly start to transfer heat to the heat dissipation grooves 3. The temperature sensor transmits the detected temperature back to the heating and cooling control system through the TEC control loop, the heating and cooling control system judges whether the target temperature is reached, and then the TEC is controlled to continue cooling or stop cooling through the TEC control loop. To continue cooling, the TEC continuously extracts heat from the sample block 1, thereby continuously cooling the biological sample in the PCR plate or PCR tube. The heat dissipation control system is processed and then acts on the heat dissipation groove 3 through the heat dissipation control loop, and heat is transferred to the outside of the heat circulation device. This process requires several cycles.

The heating and cooling control system, the central control system and the heat dissipation control system may be integrated into one control system, which is not limited herein.

Although embodiments of the present invention have been shown and described, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art without departing from the scope of the present invention.

Claims

1. A thermal cycler, comprising:

a sample block (1) provided with a blind hole array;

a heat sink (3) disposed below the N heating and cooling devices (2);

wherein, be provided with indium base sheetmetal (3000) between sample piece (1) with N heating and cooling device (2), be provided with indium base sheetmetal (3000) between N heating and cooling device (2) with radiating groove (3).

2. The thermal cycler apparatus of claim 1, wherein the indium-based metal sheet (3000) is compressed by a screw.

3. The thermal cycler apparatus of claim 1, wherein N indium-based metal sheets (3000) are disposed between the sample block (1) and the N heating and cooling devices (2).

4. The thermal cycler apparatus of claim 1, wherein a piece of indium-based metal sheet (3000) is disposed between the sample block (1) and the N heating and cooling devices (2).

5. The thermal cycler apparatus of claim 1, wherein N indium-based metal sheets (3000) are disposed between the N heating and cooling devices (2) and the heat sink (3).

6. The thermal cycler apparatus of claim 1, wherein a piece of indium-based metal (3000) is disposed between the N heating and cooling devices (2) and the heat sink (3).

7. The thermal cycler apparatus of claim 1, further comprising a spacer (4) filled between the N heating and cooling apparatuses (2).

8. The thermal cycler apparatus of claim 1, further comprising a hold down (5), the hold down (5) holding the sample block (1) down on the N heating and cooling devices (2).

9. A heat cycle device according to claim 1, characterized in that the heating and cooling device (2) is a semiconductor Cooler (TEC).