Temperature control device, amplification system, detector and detection system
By switching between open and clamped states using the temperature control unit of the temperature control device, the problem of long temperature change time in nucleic acid amplification of microfluidic chips is solved, achieving rapid temperature control and efficient amplification.
Patent Information
- Application Number
- CN202411693912.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-25
- Publication Date
- 2025-11-04
AI Technical Summary
In existing technologies, the temperature control device of microfluidic chips takes a long time to change the temperature during nucleic acid amplification, resulting in low amplification efficiency.
A temperature control device is adopted, which uses a temperature control unit configured to be in an open state and a clamping state. The temperature control drive unit controls the temperature control unit to switch between the two states, thereby realizing rapid temperature control of the amplification chamber.
This improved temperature control efficiency, thereby increasing the efficiency of nucleic acid amplification and shortening the amplification time.
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Figure CN120888397A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of microfluidic detection technology, and in particular to a temperature control device, an amplification system, a detector, and a detection system. Background Technology
[0002] Microfluidic chips integrate multiple experimental steps and are generally equipped with tiny channels and chambers arranged in a certain pattern. Different reagents are released in a certain order and flow into designated chambers through different channels to complete designated biochemical reactions, thereby achieving the purpose of sample preparation and detection.
[0003] When using microfluidic chips for nucleic acid amplification (and related detection), a temperature control device is used to regulate the temperature changes in the amplification chamber to adapt to the temperature variations required for amplification. In related technologies, the temperature of the amplification chamber is typically controlled by continuously changing the temperature of the temperature control module. However, the process of raising and lowering the temperature is time-consuming and results in low amplification efficiency.
[0004] The detector is used to automatically control microfluidic chips in order to control the preparation and detection of target substances such as nucleic acids. Summary of the Invention
[0005] This application provides a temperature control device, an amplification system, a detector, and a detection system, aimed at improving nucleic acid amplification efficiency.
[0006] The first aspect of this application provides a temperature control device for controlling the temperature of the amplification cavity of the amplification element of a microfluidic chip, comprising:
[0007] A temperature control unit, comprising two or more temperature control units configured to control the amplification chamber to have different temperatures, each temperature control unit including two temperature control modules disposed opposite to each other, the temperature control unit having an open state and a clamping state; in the open state, the two temperature control modules are spaced apart to allow the amplification element to enter the gap between the two temperature control modules; in the clamping state, the two temperature control modules are close together to clamp the amplification element within the gap between the two temperature control modules; and
[0008] A temperature control drive unit is connected to the temperature control unit to control the temperature control unit to switch between the open state and the clamping state.
[0009] In some embodiments of the temperature control device,
[0010] The temperature control drive unit is configured to drive the two temperature control modules of the temperature control unit to move synchronously in opposite directions; and / or
[0011] The temperature control drive unit is configured to control the two or more temperature control units to switch synchronously between the open state and the clamping state.
[0012] In some embodiments of the temperature control device, the temperature control unit includes:
[0013] A heat-conducting block includes a heat-exchange surface, the heat-exchange surface being used to fit against the amplification element in the clamped state to control the temperature of the amplification cavity of the amplification element;
[0014] A heat insulation pad is disposed on the side of the heat-conducting block away from the heat exchange surface; and
[0015] A heating element is disposed between the heat-conducting block and the heat-insulating pad.
[0016] In some embodiments of the temperature control device, the temperature control drive unit includes:
[0017] A separation drive mechanism is configured to apply a first force to the two temperature control modules to move them apart, thereby controlling the temperature control units to switch from the clamped state to the open state and to release the first force; and
[0018] The reset drive mechanism is configured to apply a second force to the two temperature control modules to bring them closer together, thereby controlling the temperature control unit to switch from the open state to the clamping state when the separation drive mechanism releases the first force.
[0019] In some embodiments of the temperature control device, the separation drive mechanism includes:
[0020] Temperature zone fixing plate, wherein the two temperature control modules of the temperature control unit are respectively disposed on two temperature zone fixing plates that are relatively spaced apart;
[0021] Temperature-controlled drive motor; and
[0022] A cam is driven and connected to the temperature control drive motor to rotate under the drive of the temperature control drive motor. The cam is drivably engaged with the two temperature zone fixing plates. The cam drives the two temperature zone fixing plates and the two temperature control modules on them to move closer or further away from each other to apply the first force to the two temperature control modules and release the first force.
[0023] In some embodiments of the temperature control device, the separation drive mechanism further includes:
[0024] Bearings are mounted on the temperature zone fixing plate; and
[0025] A pin is supported on the bearing, and the cam abuts against the pin to drive the two temperature zone fixing plates and the two temperature control modules on them to move closer or further apart.
[0026] In some embodiments of the temperature control device, the separation drive mechanism further includes:
[0027] Linear bearing, mounted on the temperature zone fixing plate; and
[0028] The movable shaft, supported on the linear bearing, is configured to guide the two temperature zone fixing plates and the two temperature control modules on them toward or away from each other.
[0029] In some embodiments of the temperature control device, the temperature control drive unit further includes a position detection device, which is configured to detect whether the temperature control module has reached a preset position required by the temperature control unit in the open state. The separation drive mechanism is coupled to the position detection device and configured to stop operating if the detection result of the position detection device is yes during the process of switching the temperature control unit from the clamped state to the open state.
[0030] In some embodiments of the temperature control device, the reset drive mechanism includes a spring configured to apply a force toward the temperature control module disposed thereon to the temperature zone fixing plate to apply the second force to the temperature control module.
[0031] In some embodiments of the temperature control device, the temperature control device further includes a heat dissipation unit configured to reduce the temperature of the temperature control unit that forms a lower temperature zone among the two or more temperature control units.
[0032] In some embodiments of the temperature control device, the heat dissipation section includes:
[0033] Fan; and
[0034] The air outlet concentration block has a built-in air duct, which has an air inlet and an air outlet. The air inlet is connected to the outlet of the fan, and the air outlet is opposite to the two temperature control modules of the temperature control unit that forms the lower temperature zone.
[0035] In some embodiments of the temperature control device,
[0036] The heat dissipation unit includes two or more fans, and the built-in air duct has two or more air inlets corresponding one-to-one with the two or more fans; and / or
[0037] The built-in air duct has a gradually narrowing flow channel section.
[0038] A second aspect of this application provides an amplification apparatus, comprising:
[0039] The temperature control device described in the first aspect of this application; and
[0040] A holding device includes a holding portion for holding the microfluidic chip, the holding portion being variably positioned so that the amplification portion of the microfluidic chip moves between different temperature control units when two or more temperature control units are in an open state.
[0041] A third aspect of this application provides a detector, including the amplification device of the second aspect of this application.
[0042] A fourth aspect of this application provides a detection system, comprising:
[0043] A microfluidic chip includes an amplification element having an amplification cavity; and
[0044] The testing instrument described in the third aspect of this application.
[0045] According to the temperature control device of this application, two or more temperature control units are configured to control the amplification chamber at different temperatures. Each temperature control unit has an open state and a clamping state. A temperature control drive unit is driven and connected to the temperature control unit, controlling the temperature control unit to switch between the open state and the clamping state. In the open state, the amplification element can enter the gap between the two temperature control modules of the corresponding temperature temperature control unit. In the clamping state, the corresponding temperature temperature control unit can control the temperature of the amplification element clamped between the two temperature control modules to rapidly reach the required temperature, and then allow the amplification element to enter the next required temperature temperature control unit, repeating this process until the nucleic acid amplification process is complete. Since there is no heating or cooling process by the temperature control modules, the amplification element 205 can be directly controlled at a temperature close to the controlled temperature after entering the corresponding temperature control unit, thereby improving temperature control efficiency and thus amplification efficiency.
[0046] The amplification system, detector, and detection system of this application include the temperature control device of this application, and have the advantages of the temperature control device of this application.
[0047] Other features and advantages of this application will become clear from the following detailed description of exemplary embodiments with reference to the accompanying drawings. Attached Figure Description
[0048] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0049] Figure 1 This is a three-dimensional structural diagram of the detection system in the embodiments of this application.
[0050] Figure 2 This is a three-dimensional structural diagram of the microfluidic chip in the embodiments of this application.
[0051] Figure 3 This is a schematic diagram of the exploded structure of the microfluidic chip in the embodiments of this application.
[0052] Figure 4 This is a schematic diagram of the combined structure of the microfluidic chip body and rotor in the embodiments of this application.
[0053] Figure 5 This is a three-dimensional structural diagram of the detector in the embodiments of this application.
[0054] Figure 6 This is a three-dimensional structural diagram of the detector when the first side plate is omitted in the embodiment of this application.
[0055] Figure 7 This is a three-dimensional structural diagram of the base and holding device in the embodiments of this application.
[0056] Figure 8 This is a schematic diagram of the structure of the holding drive unit of the holding device in the embodiments of this application.
[0057] Figure 9 This is a schematic diagram of the structure of the holding part of the holding device in the embodiments of this application.
[0058] Figure 10 This is a schematic diagram of the combined structure of the holding part of the holding device and the microfluidic chip in the embodiments of this application.
[0059] Figure 11 This is a three-dimensional structural diagram of the temperature control device in the embodiments of this application.
[0060] Figure 12 This is an exploded structural diagram of the holding part of the temperature control device in the embodiments of this application.
[0061] Figure 13 This is a three-dimensional structural diagram of the temperature control unit of the heating part of the temperature control device in the embodiment of this application, showing its two temperature control modules 63 in an open state with their distances from each other.
[0062] Figure 14 This is a three-dimensional structural diagram of the temperature control unit of the heating part of the temperature control device in the embodiment of this application, showing the clamping state in which its two temperature control modules 63 are close to each other.
[0063] Figure 15 This is a schematic diagram of the structure when the temperature control device and the microfluidic chip are used together in the embodiments of this application.
[0064] Figure 16 This is a partial structural diagram of the temperature control device and the microfluidic chip in the embodiments of this application. Explanation of reference numerals in the attached figures:
[0065] 100. Detection system;
[0066] 10. Detector; 102. Extraction device; 103. Liquid flow control device;
[0067] 1. Base; 11. Base plate; 12. First side plate; 13. Second side plate; 14. Mounting position;
[0068] 2. Holding device; 22. Holding drive unit; 220. Holding drive motor fixing plate; 221. Gear; 222. Rack fixing plate; 223. Holding drive motor; 224. Rack; 23. Holding unit; 230. Slider; 230a. Guide rail; 231. Pallet body; 232. Pallet limiting block; 232a. Guide groove; 233. Pallet positioning block; 234. Spring;
[0069] 3. Piercing device; 31. Support; 32. Piercing component; 33. Lifting mechanism; 36. Linkage mechanism;
[0070] 4. Rotary valve device;
[0071] 5. Pump assembly; 51. Drive pump; 52. Connecting nozzle;
[0072] 6. Temperature control device; 61. Support frame; 62. Temperature control drive unit; 620. Temperature zone fixing plate; 621. Temperature control drive motor; 622. Cam; 623. Bearing; 624. Linear bearing; 625. Spring; 626. Photoelectric switch baffle; 627. Photoelectric switch; 628. Pin; 629. Temperature control drive motor fixing plate; 6201. Movable shaft; 63. Temperature control module; 630. Heat-conducting block; 631. Heat insulation pad; 632. Heating element; 64. Heat dissipation unit; 640. Fan; 641. Fixing component; 642. Air outlet concentration block; 642a. Built-in air duct;
[0073] 7. Ultrasonic device; 71. Ultrasonic support; 72. Ultrasonic transducer; 73. Ultrasonic resetting mechanism;
[0074] 8. Magnetic suction device;
[0075] 9. Detection device; 901. Detection optical fiber;
[0076] 20. Microfluidic chip; 201. Body; 201a. Storage cavity; 201b. Mounting slot; 202. Base; 202a. Reaction chamber; 202d. Positioning block; 202e. First seat; 202f. Second seat; 202g. Third seat; 203. Switching valve; 203a. Rotor; 203b. Valve stem; 203c. Valve seat; 203d. Seat; 203e. Gasket; 203f, Valve internal flow channel; 203g, Valve cover; 204, Top cover; 204a, Sample inlet; 204b, Connecting port; 204c, Puncture needle; 204d, Connecting rib; 204f, Rib; 204g, Cover body; 204h, Ring component; 204j, Ventilation channel; 205, Amplification component; 205a, Amplification chamber; 206, Cover plate; 206a, Through hole; 207, Temperature control area;
[0077] X: forward / backward direction; Y: left / right direction; Z: up / down direction. Detailed Implementation
[0078] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit this application or its application or use. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.
[0079] Techniques, methods, and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and equipment should be considered part of the specification.
[0080] In the description of this application, it should be understood that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore should not be construed as limiting the scope of protection of this application.
[0081] In the description of this application, it should be understood that the directional terms "inner" and "outer" refer to the inner and outer sides relative to the outline of each component itself; while the directional terms such as "front," "back," "up," "down," "left," "right," "horizontal," "vertical," "perpendicular," and "top," "bottom," etc., indicate the orientation or positional relationship, which is usually based on Figure 1 , Figure 5 and Figure 6 The directions or positional relationships shown include: the up and down directions are... Figure 1 Figure 5 and Figure 6The coordinate axis Z is used to represent this, which can be called the vertical direction Z, or the second direction Z; at the same time, the relative arrangement direction of the holding device 2 and the temperature control device 6 is taken as the front-back direction. Figure 1 , Figure 5 and Figure 6 The coordinate axis X is used to represent this, which can be called the front-back direction X, or the first direction X. Here, the position of the holding device 2 relative to the temperature control device 6 is front, and the position of the temperature control device 6 relative to the holding device 2 is rear. Furthermore, the direction perpendicular to the first direction X and the second direction Z is defined as the left-right direction. Figure 1 , Figure 5 and Figure 6 The coordinate axis Y is used to represent the left and right directions, or the third direction Y. The left and right directions are defined when facing forward.
[0082] Furthermore, the technical features involved in the different embodiments of this application described below can be combined with each other as long as they do not conflict with each other.
[0083] like Figures 1 to 16 As shown, this application embodiment provides a temperature control device 6 for controlling the temperature of the amplification cavity 205a of the amplification element 205 of the microfluidic chip 20. The temperature control device 6 includes a temperature control unit and a temperature control drive unit 62.
[0084] Two or more temperature control units are configured to control different temperatures in the amplification chamber 205a. Each temperature control unit includes two temperature control modules 63 arranged opposite each other, and has an open state and a clamping state. In the open state, the two temperature control modules 63 are spaced apart to allow the amplification element 205 to enter the gap between the two temperature control modules 63. In the clamping state, the two temperature control modules 63 are brought closer together to clamp the amplification element 205 within the gap between the two temperature control modules 63. A temperature control drive unit 62 is drivenly connected to the temperature control unit to control the switching between the open and clamping states.
[0085] According to the temperature control device 6 of this application, two or more temperature control units are configured to control the amplification chamber 205a to have different temperatures. Each temperature control unit has an open state and a clamping state. A temperature control drive unit 62 is driven and connected to the temperature control unit, controlling the switching between the open and clamping states. In the open state, the amplification piece 205 can enter the gap between two temperature control modules 63 of the corresponding temperature temperature control unit. In the clamping state, the corresponding temperature temperature control unit can control the temperature of the amplification piece 205 clamped within the gap between the two temperature control modules 63 to rapidly reach the required temperature. Then, the amplification piece 205 enters the next required temperature temperature control unit, repeating this process until the nucleic acid amplification process is complete. Since there is no heating or cooling process of the temperature control modules, the amplification piece 205 can be directly controlled at a temperature close to the controlled temperature after entering the corresponding temperature control unit, thereby improving temperature control efficiency and thus amplification efficiency.
[0086] like Figures 11 to 14 As shown, in some embodiments of the temperature control device 6, the temperature control drive unit 62 is configured to drive two temperature control modules 63 of the temperature control unit to move synchronously in opposite directions; and / or the temperature control drive unit 62 is configured to control two or more temperature control units to switch synchronously between an open state and a clamping state.
[0087] The temperature control drive unit 62 is configured to drive the two temperature control modules 63 of the temperature control unit to move synchronously in opposite directions. This facilitates rapid and accurate switching of the temperature control unit's state and also reduces the number of drive components, simplifying the structure of the temperature control drive unit. The temperature control drive unit 62 is also configured to control the synchronous switching of two or more temperature control units between open and clamped states. This helps avoid waiting or interference when the expansion component 205 moves between different temperature control units, further reducing the number of drive components and simplifying the structure of the temperature control drive unit.
[0088] For example, in Figures 11 to 16 In the temperature control device 6 shown, its temperature control drive unit 62 drives the two temperature control modules 63 of each of the two temperature control units to move synchronously in opposite directions, and at the same time controls the two temperature control units to switch synchronously between the open state and the clamping state.
[0089] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the temperature control unit includes a heat-conducting block 630, a heat-insulating pad 631, and a heating element 632. The heat-conducting block 630 includes a heat exchange surface for contacting the amplification element 205 in a clamped state to control the temperature of the amplification chamber 205a of the amplification element 205. The heat-insulating pad 631 is disposed on the side of the heat-conducting block 630 away from the heat exchange surface. The heating element 632 is disposed between the heat-conducting block 630 and the heat-insulating pad 631.
[0090] The heat-conducting block 630 facilitates uniform heating of the amplification chamber 205a. The heat-insulating pad 631 allows more heat generated by the heating element 632 to be transferred to the amplification element 205 through the heat-conducting block 630, thereby saving energy.
[0091] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the temperature control drive unit 62 includes a separation drive mechanism and a reset drive mechanism. The separation drive mechanism is configured to apply a first force to the two temperature control modules 63 to move them away from each other in order to control the temperature control unit to switch from a clamped state to an open state and to release the first force. The reset drive mechanism is configured to apply a second force to the two temperature control modules 63 to move them closer to each other in order to control the temperature control unit to switch from an open state to a clamped state when the separation drive mechanism releases the first force.
[0092] By combining the separation drive mechanism and the reset drive mechanism, the state switching of the temperature control unit can be carried out smoothly, and it is also beneficial to provide a stable clamping force to the expansion component 205 without control in the clamping state.
[0093] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the separation drive mechanism includes a temperature zone fixing plate 620, a motor 621, and a cam 622. Two temperature control modules 63 of the temperature control unit are respectively disposed on two temperature zone fixing plates 620 spaced apart from each other. The cam 622 is drivenly connected to the motor 621 to rotate under the drive of the motor 621. The cam 622 is drivably engaged with the two temperature zone fixing plates 620. The cam 622 drives the two temperature zone fixing plates 620 and the two temperature control modules 63 on them to move closer or further apart to apply a first force to and release a first force to the two temperature control modules 63.
[0094] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the separation drive mechanism further includes a bearing 623 and a pin 628. The bearing 623 is disposed on the temperature zone fixing plate 620. The pin 628 is supported on the bearing 623. The cam 622 abuts against the pin 628 to drive the two temperature zone fixing plates 620 and the two temperature control modules 63 on them to move closer or further apart.
[0095] Pin 628 drives the two temperature zone fixing plates 620 and the two temperature control modules 63 on them to move closer or further apart, making the cam 622 drive the temperature zone fixing plates 620 and the two temperature control modules 63 on them more smoothly, which helps to prevent jamming in the transmission path.
[0096] like Figures 11 to 16As shown, in some embodiments of the temperature control device 6, the separation drive mechanism further includes a linear bearing 624 and a movable shaft 6201. The linear bearing 624 is disposed on the temperature zone fixing plate 620. The movable shaft 6201 is supported on the linear bearing 624 and is configured to guide the two temperature zone fixing plates 620 and the two temperature control modules 63 on them to move closer or further apart.
[0097] The linear bearing 624 and the movable shaft 6201 are provided to guide the movement of the temperature zone fixing plate 620 and to facilitate the smooth movement of the temperature zone fixing plate 620.
[0098] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the temperature control drive unit 62 further includes a position detection device. The position detection device is configured to detect whether the temperature control module 63 has reached the preset position required for the temperature control unit to be in the open state. The separation drive mechanism is coupled to the position detection device and configured to stop operating if the detection result of the position detection device is yes during the process of switching the temperature control unit from the clamped state to the open state.
[0099] The position detection device facilitates control of the position of the temperature control device 63 when it is in the open state. Figures 11 to 16 In the illustrated embodiment, the position detection device includes, for example, a photoelectric switch baffle 626 and a photoelectric switch 627.
[0100] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the reset drive mechanism includes a spring 625, which is configured to apply a force to the temperature zone fixing plate 620 toward the side of the temperature control module 63 disposed thereon to apply a second force to the temperature control module 63.
[0101] A second force is applied to the temperature control module 63 by spring 625. By selecting the operating parameters of the spring, a suitable clamping force can be obtained for the expansion component 205 in the clamping state of the temperature control unit. This reset drive mechanism has a simple structure and is easy to implement.
[0102] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the temperature control device 6 further includes a heat dissipation section 64, which is configured to reduce the temperature of the temperature control unit that forms a lower temperature zone among two or more temperature control units.
[0103] The heat dissipation section 64 helps maintain the lower temperature zone at its appropriate temperature.
[0104] like Figures 11 to 16As shown, in some embodiments of the temperature control device 6, the heat dissipation unit 64 includes a fan 640 and an air outlet concentration block 642. The air outlet concentration block 642 has a built-in air duct 642a, which has an air inlet and an air outlet. The air inlet is connected to the outlet of the fan 640, and the air outlet is opposite to the two temperature control modules 63 of the temperature control unit that form a lower temperature zone.
[0105] The air outlet concentration block 642 is set up to make it easier to direct the air outlet of the fan 640 to the part that needs temperature control, thereby making the lower temperature area reach its appropriate temperature more quickly.
[0106] like Figures 11 to 16 As shown, in some embodiments of the temperature control device 6, the heat dissipation unit 64 includes two or more fans 640, the built-in air duct 642a has two or more air inlets corresponding one-to-one with the two or more fans 640; and / or the built-in air duct 642a has a tapered flow channel section.
[0107] Equipped with two or more fans 640 and corresponding built-in air ducts 642a, it is beneficial to provide suitable airflow for regulating the temperature of lower temperature zones. The built-in air duct 642a has a tapered flow section, which helps to increase the air velocity at the outlet, thereby facilitating faster temperature regulation of lower temperature zones.
[0108] like Figures 1 to 16 As shown, this application embodiment also provides an amplification device, including a temperature control device 6 and a holding device 2 according to this application embodiment. The holding device 2 includes a holding portion 23 for holding a microfluidic chip 20. The holding portion 23 is variably positioned so that the amplification portion 205 of the microfluidic chip 20 can move between different temperature control units when two or more temperature control units are in the open state.
[0109] By cooperating with the holding device 2, the amplification unit 205 can automatically switch between the temperature control unit 6 and the temperature control unit, thereby further improving the amplification efficiency.
[0110] like Figures 1 to 16 As shown in the figure, this application embodiment also provides a detector 10, which includes the amplification device of this application embodiment.
[0111] like Figures 1 to 16 As shown, this application also provides a detection system 100, including a microfluidic chip 20 and a detector 10 according to an embodiment of this application. The microfluidic chip 20 includes an amplification element 205, which has an amplification cavity 205a.
[0112] The amplification system, detector, and detection system of this application include the temperature control device of this application, and have the advantages of the temperature control device of this application.
[0113] The following combination Figures 1 to 16Further explanation of the detection system 100, its microfluidic chip 20, and the detector 10 of the embodiments of this application, as well as the amplification device, temperature control device 6, and holding device 2 of the detector 10.
[0114] Figures 1 to 6 The detection system 100 of this application, its microfluidic chip 20, and the detector 10 are illustrated by way of example.
[0115] Reference Figures 1 to 6 In this application, the detection system 100 includes a microfluidic chip 20 and a detector 10. The detector 10 is used to clamp, fix, and manipulate the microfluidic chip 20 to achieve automatic control of the microfluidic detection process.
[0116] To make it easier to understand, let's first combine... Figures 2 to 4 The structure of the microfluidic chip 20 is described below. Although the microfluidic chip 20 of this application can be used to implement various detection processes similar to nucleic acid detection, the following description will primarily focus on its use in nucleic acid detection to simplify the explanation. The nucleic acid detection process generally includes nucleic acid extraction, nucleic acid amplification, and nucleic acid detection. Specifically, nucleic acid is first extracted from a sample containing cells (e.g., whole blood or serum) through steps such as lysis and purification. Then, the extracted nucleic acid is amplified, and the target nucleic acid is detected during the amplification process.
[0117] See Figures 2 to 4 In some embodiments, the microfluidic chip 20 includes a body 201, a top cover 204, a cover plate 206, a base 202, an amplification component 205, and a switching valve 203.
[0118] Body 201 is used to store fluids required for various nucleic acid detection experiments, such as samples and lysis buffers. See also Figure 4 The main body 201 is provided with a storage cavity 201a for storing the required fluid. Specifically, as shown in the figure... Figure 4 As shown, in some embodiments, the body 201 is provided with multiple storage cavities 201a, which are arranged side by side for storing different fluids. For example, some storage cavities 201a are used to store samples such as whole blood; these storage cavities 201a can be called sample cavities. Other storage cavities 201a are used to store reagents (e.g., various reaction reagents required for preparing nucleic acids from samples, as well as auxiliary reagents such as magnetic beads, washing solutions, and elution solutions); these storage cavities 201a can be called reagent cavities. More specifically, as... Figure 4 As shown, in some embodiments, the body 201 is cylindrical, and all storage cavities 201a are arranged at intervals on the same circumference of the body 201.
[0119] A sealing membrane (not shown in the figure) is provided at the end of the storage cavity 201a to seal the end opening of the storage cavity 201a, thereby sealing the fluid in the storage cavity 201a and effectively preventing accidental leakage or spillage. This facilitates the transportation of the microfluidic chip 20 and allows for control over the flow of fluid only when needed, improving controllability and safety. Specifically, as shown... Figure 4 As shown, in some embodiments, the storage cavity 201a is provided with a sealing membrane at only one end, and the other end is directly sealed by the end wall of the body 201. In this case, the storage cavity 201a is a groove with a bottom.
[0120] When the sealing membrane is punctured, the storage cavity 201a is connected to the outside atmosphere, and the fluid inside the storage cavity 201a can flow out to the outside of the storage cavity 201a.
[0121] The sealing film is punctured by a puncture needle 204c. In some embodiments, the puncture needle 204c is disposed on the top cover 204.
[0122] The top cover 204 provides a mounting base for the puncture needle 204c. For example... Figure 2 and Figure 3 As shown, a top cover 204 is placed over the end of the main body 201, and a piercing needle 204c is provided on its wall facing the main body 201. Each piercing needle 204c corresponds to a storage cavity 201a and is connected to the top cover 204 via a connecting rib 204d. Initially, there is a gap between the piercing needle 204c and the sealing membrane, and they do not contact each other. However, when the connecting rib 204d is broken, the piercing needle 204c detaches from the top cover 204 and moves towards the storage cavity 201a, piercing the sealing membrane on the storage cavity 201a, thus opening the storage cavity 201a to the atmosphere.
[0123] Specifically, such as Figures 2 to 4 As shown, in some embodiments, the top cover 204 includes a cover body 204g and an annular member 204h.
[0124] The cover 204g is positioned on top of the main body 201 and snaps into it, thus securing the cover 204g to the main body 201. The cover 204g has a sample inlet 204a, which communicates with one of the multiple storage chambers 201a (i.e., the sample chamber) to add the sample to be tested into the corresponding storage chamber 201a. Furthermore, the cover 204g has a connecting port 204b. The connecting port 204b communicates with a connecting nozzle 52 for connection to the drive pump 51, allowing the drive pump 51 to drive fluid to flow between different chambers of the microfluidic chip 20, thereby achieving fluid transfer.
[0125] The outer edge of the annular member 204h is connected to the top wall of the cover 204g via multiple connecting ribs 204d. Meanwhile, the inner edge of the annular member 204h is connected to a stop member (not shown) via multiple ribs 204f. The stop member is roughly annular and extends from the annular member 204h toward the body 201.
[0126] A piercing needle 204c is provided on the surface of the annular member 204h facing the body 201. The piercing needle 204c is located radially between the outer edge of the annular member 204h and the stop member, and includes a first needle segment (not shown in the figure) and a second needle segment (not shown in the figure). The radial dimension of the second needle segment is larger than that of the first needle segment. The first needle segment is connected to the annular member 204h through the second needle segment, and its bottom end is constructed to be sharp so as to pierce the sealing membrane. A venting channel 204j is provided inside the piercing needle 204c, penetrating the first needle segment and extending into the interior of the second needle segment, and a vent hole (not shown in the figure) communicating with the venting channel 204j is provided on the side wall of the second needle segment, so that the piercing needle 204c can communicate the storage cavity 201a with the outside atmosphere after piercing the sealing membrane.
[0127] The connecting ribs 204d and ribs 204f can be crushed to separate the annular part 204h from the cover 204 and the stop from the annular part 204, so that the piercing needle 204c can pierce the sealing film before extraction begins and cooperate with the cover 206 to reseal the storage cavity 201a after extraction.
[0128] A cover plate 206 is disposed between the top wall of the main body 201 and the top cover 204, and has a through hole 206a that allows the piercing needle 204c to pass through. The diameter of the through hole 206a is larger than the outer diameter of the first needle segment and slightly smaller than the outer diameter of the second needle segment. When the second needle segment is inserted into the through hole 206a under external force, the second needle segment and the through hole 206a are press-fitted. In this case, the vent hole on the second needle segment is blocked by the cover plate 206, which can realize the resealing of the storage cavity 201a to prevent waste liquid leakage and pollution.
[0129] When using the microfluidic chip 20, pressure is applied to the annular part 204h on the top cover 204, causing the connecting rib 204d to break. The annular part 204h drives each piercing needle 204c to detach from the cover 204g and press against the sealing film on the storage cavity 201a, causing the piercing needle 204c to pierce the sealing film. After the piercing needle 204c pierces the sealing film, the stop member abuts against the body 201 to prevent the piercing needle 204c from moving down too far. The gas in the storage cavity 201a is connected to the atmosphere through the piercing needle 204c. After the extraction step is completed, pressure is continued to be applied to the annular part 204h. Since the stop is blocked by the body 201 and cannot continue to move downward, when the pressure reaches a certain level, the downward pressure will break the rib 204f connecting the annular part 204h and the stop, causing the annular part 204h to separate from the stop. At this time, the stop no longer hinders the downward movement of the puncture needle 204c. Therefore, the annular part 204h and each puncture needle 204c can be further pressed against the sealing film under the action of external force until the second needle segment is interference-fitted with the through hole on the cover plate 206. The cover plate 206 blocks the vent hole on the second needle segment, realizing the resealing of the storage cavity 201a.
[0130] In summary, the piercing needle 204c on the top cover 204 is used to pierce the sealing membrane on the storage chamber 201a, allowing the storage chamber 201a to communicate with the atmosphere, thus providing conditions for fluid flow within the storage chamber 201a. The stop on the top cover 204 is used to cooperate with the body 201, keeping the piercing needle 204c in the pierced position before the extraction step ends, connecting the storage chamber 201a to the atmosphere without excessive downward movement, and is also used to cooperate with the piercing element 32 of the piercing device 3 after extraction to break the rib 204f. The cover plate 206 is used to cooperate with the piercing needle 204c to seal the storage chamber 201a after the extraction step to prevent waste liquid leakage.
[0131] The base 202 is located on the side of the main body 201 away from the top cover 204, and is used to receive fluid flowing out of the storage cavity 201a to complete the extraction of target substances such as nucleic acids. Figure 3 As shown, a reaction chamber 202a is provided on the base 202. The reaction chamber 202a is the site for extracting and preparing the target analyte. The sample and reagents enter the reaction chamber 202 in sequence, react, and the target analyte is obtained. The reaction chamber 202a is located at the bottom of the base 202 and protrudes downward, forming a spherical crown shape. This arrangement allows the reaction chamber 202a to be coupled with the ultrasonic device 7 and magnetic suction device 8 of the detector 10, which will be mentioned below.
[0132] In addition, such as Figure 3 As shown, a positioning block 202d is provided on the base 202. The positioning block 202d is used to cooperate with the holding device 2 of the detector 10 to realize the installation and fixation of the microfluidic chip 20 on the detector 10.
[0133] The base 202 can be a one-piece structure or a separate structure. See also Figure 3 In some embodiments, the base 202 adopts a split structure, comprising a first base 202e, a second base 202f, and a third base 202g. The first base 202e is connected to the main body 201, while the second base 202f and the third base 202g are spaced apart and disposed on the side of the first base 202e away from the main body 201, and are detachably connected to the main body 201 by means of engagement or other methods. The aforementioned reaction chamber 202a is disposed on the first base 202e and protrudes relative to the second base 202f and the third base 202g on the side away from the main body 201. Simultaneously, the aforementioned positioning block 202d is disposed on the second base 202f and the third base 202g, and is located on the outer peripheral surface of the second base 202f and the third base 202g. The positioning blocks 202d on the second seat 202f and the third seat 202g are positioned opposite each other to achieve a more stable installation of the microfluidic chip 20 on the holding device 2.
[0134] The amplification element 205 is connected to one side of the main body 201 and extends outward to provide a site for the amplification of the target analyte, thus meeting the detection needs of target analytes such as nucleic acids that require amplification before detection. Figure 2 and Figure 3 As shown, in some embodiments, the amplification element 205 is pluggably connected to the side of the body 201 and has an amplification chamber 205a inside. The amplification chamber 205a is the site where the amplification reaction occurs. The target substances such as nucleic acids prepared in the reaction chamber 202a are sent to the amplification chamber 205a and amplified therein for detection.
[0135] like Figure 2 and Figure 3 As shown, in some embodiments, the amplification element 205 is in the form of a thin sheet, so that the amplification element 205 can fully contact and exchange heat with the temperature control device 6 of the detector 10 mentioned below, thereby achieving a rapid heating and cooling process.
[0136] The switching valve 203 is disposed on the body 201 and is used to control the on / off relationship between the chambers of the microfluidic chip 20 (e.g., storage chamber 201a, reaction chamber 202a and amplification chamber 205a) so as to control the fluid in the microfluidic chip 20 to flow in the required order, thereby successfully completing the extraction and amplification steps.
[0137] like Figures 2 to 4 As shown, in some embodiments, the body 201 has a mounting groove 201b at its center, the switching valve 203 is disposed in the mounting groove 201b, and includes a rotor 203a and a valve cover 203g.
[0138] The valve cover 203g is connected to the circumferential sidewall of the mounting groove 201b. The rotor 203a is rotatably disposed within the mounting groove 201b and includes a valve seat 203c and a valve stem 203b. The valve seat 203c includes a seat body 203d and a gasket 203e. The bottom shape of the gasket 203e is the same as that of the seat body 203d, both being circular. The seat body 203d and the gasket 203e are fixedly disposed together. The combined structure of the seat body 203d and the gasket 203e includes an internal valve flow channel 203f. The radial dimension of the valve stem 203b is smaller than that of the seat 203d, and one end of it is fixedly connected to the seat 203d, while the other end extends through the valve cover 203g, the cover plate 206 and the top cover 204 for connection with the rotary valve device 4 of the detector 10 mentioned below, so that it can rotate under the drive of the rotary valve device 4, thereby connecting the flow channel 203f inside the valve with different chambers of the microfluidic chip 20 to realize the switching of the valve position of the switching valve 203.
[0139] Rotating valve device 4 rotates valve stem 203b, which in turn rotates seat 203d and gasket 203e, causing the internal flow channel 203f to change position and switch between connecting reaction chamber 202a and different chambers, thus completing the liquid flow transfer during the detection process. For example, when internal flow channel 203f connects reaction chamber 202a to different storage chambers 201a, the sample and reagents in storage chamber 201a can flow into reaction chamber 202a sequentially under external force, realizing the extraction process. As another example, when internal flow channel 203f connects reaction chamber 202a to amplification chamber 205a, the target analyte prepared in reaction chamber 202a can flow into amplification chamber 205a under external force for amplification.
[0140] Among them, by Figure 3 and Figure 4 It is known that in some embodiments, the outer surface of the valve stem 203b is a polygonal surface (e.g., a hexagonal surface), which makes it easier to achieve a non-rotatable connection between the valve stem 203b and the rotary valve component of the rotary valve device 4, thereby facilitating the rotary valve device 4 to reliably drive the valve stem 203b to rotate.
[0141] Based on the above description of the structure of the microfluidic chip 20, the structure of the detector 10 will be described next.
[0142] Figures 5 to 6 The structure of the detector 10 is shown as an example.
[0143] See Figures 5 to 6 In order to achieve fully automated control of the microfluidic detection process based on the microfluidic chip 20, in some embodiments, the detector 10 includes a base 1, a holding device 2, a piercing device 3, a rotary valve device 4, a pump assembly 5, a temperature control device 6, an ultrasonic device 7, a magnetic suction device 8, and a detection device 9.
[0144] The base 1 provides an installation foundation for other modules of the detector 10, such as the holding device 2, the piercing device 3, the rotary valve device 4, the pump assembly 5, the temperature control device 6, the ultrasonic device 7, the magnetic suction device 8, and the detection device 9.
[0145] The holding device 2 is used to hold the microfluidic chip 20 so as to realize the installation and fixation of the microfluidic chip 20 on the detector 10, and facilitate other modules of the detector 10 to control the microfluidic chip 20.
[0146] The puncture device 3 is used to control the puncture of the sealing film on the storage chamber 201a of the microfluidic chip 20, thereby providing conditions for the flow of fluid in the microfluidic chip 20. In some embodiments, the puncture device 3 includes a puncture member 32, which is movably disposed vertically. During vertical movement, the puncture needle 204c is driven to move relative to the storage chamber 201a of the microfluidic chip 20 mounted on the holding device 2, puncturing the sealing film on the storage chamber 201a. Furthermore, in the microfluidic chip 20... Figures 2 to 4 As shown, when the cover plate 206 is also present, after the piercing needle 204c punctures the sealing film, the piercing member 32 further drives the piercing needle 204c to move towards the holding device 2, so that the piercing needle 204c and the cover plate 206 of the microfluidic chip 20 together seal the storage cavity 201a, thereby achieving the resealing of the storage cavity 201a to prevent leakage of waste liquid in the storage cavity 201a. The position of the piercing member 32 when the piercing needle 204c punctures the sealing film on the storage cavity 201a is called the piercing position; and the position of the piercing member 32 when the piercing needle 204c and the cover plate 206 of the microfluidic chip 20 reseale the storage cavity 201a together is called the sealing position.
[0147] The rotary valve device 4 is used to drive the rotor 203a of the switching valve 203 of the microfluidic chip 20 to rotate, thereby switching the valve position of the switching valve 203 and enabling the fluid in the microfluidic chip 20 to flow sequentially. In some embodiments, the rotary valve device 4 includes a rotary valve element and a rotary valve drive mechanism. The rotary valve element is movably arranged vertically to be detachably connected to the rotor 203a of the switching valve 203. The rotary valve drive mechanism is drivenly connected to the rotary valve element to drive the rotor 203a to rotate when the rotary valve element is connected to the rotor 203a, thereby achieving automatic switching of the valve position of the switching valve 203.
[0148] Pump assembly 5 is used to communicate with the communication port 204b of microfluidic chip 20 and drive fluid flow within microfluidic chip 20. In some embodiments, pump assembly 5 includes a communication nozzle 52 and a drive pump 51. The communication nozzle 52 is movably disposed to be detachably connected to the communication port 204b of microfluidic chip 20. The drive pump 51 communicates with the communication nozzle 52 to drive fluid flow within microfluidic chip 20 when the communication nozzle 52 is connected to the communication port 204b.
[0149] like Figures 11 to 16 As shown, the temperature control device 6 is used to control the temperature of the portion 207 of the amplification component 205 of the microfluidic chip 20 to meet the temperature requirements during the microfluidic detection process. In some embodiments, the temperature control device 6 includes a temperature control unit, which includes two temperature control modules 63 that are opposite to each other and movable relative to each other. When the amplification component 205 of the microfluidic chip 20 is inserted, the two temperature control modules 63 clamp the amplification component 205 and control the temperature of the portion 207 of the amplification component 205 to be controlled. The portion 207 to be controlled includes an amplification cavity 205a. During the operation of the detector 10 on the microfluidic chip 20, the amplification component 205 of the microfluidic chip 20 is inserted between the two temperature control modules 63, so that the portion 207 to be controlled comes into contact with the heat exchange surfaces of the heat-conducting blocks 630 of the two temperature control modules 63, so that when amplification is required, the two temperature control modules 63 can be used to heat or cool the amplification cavity 205a to provide suitable temperature conditions for the amplification process.
[0150] In the temperature control device 6, the number of temperature control units can be two or more. For example, in some embodiments, the temperature control device 6 includes at least two temperature control units, and these at least two temperature control units are arranged side by side along the vertical direction. In this case, each temperature control unit can form a temperature zone. Therefore, by arranging at least two temperature control units side by side along the vertical direction, at least two temperature zones can be formed. This facilitates temperature control of the part to be controlled 207 within different temperature ranges, so as to complete the amplification process more efficiently and achieve better amplification results.
[0151] In the case where the temperature control device 6 includes at least two temperature control units arranged side by side along the vertical direction, in order to facilitate the switching of the microfluidic chip 20 between different temperature control units, in some embodiments, the holding device 2 includes a holding part 23 configured to be movable vertically and a holding drive part 22 that drives the holding part 23 to move vertically. In this way, during the temperature control process, the holding drive part 22 of the holding device 2 can be controlled to drive the holding part 23 to move vertically back and forth, and the holding part 23 drives the microfluidic chip 20 to move vertically back and forth, continuously switching between different temperature zones corresponding to different temperature control units.
[0152] The ultrasonic device 7 is used to apply ultrasonic excitation to the reaction chamber 202a of the microfluidic chip 20 to assist the extraction process. See also Figure 5 and Figure 6In some embodiments, the ultrasonic device 7 includes an ultrasonic transducer 72, which is movably disposed between a contact position and a clearance position. In the contact position, the ultrasonic transducer 72 contacts the outer wall of the reaction chamber 202a of the microfluidic chip 20, transmitting vibrations to the reaction chamber 202a; in the clearance position, the ultrasonic transducer 72 is separated from the outer wall of the reaction chamber 202a of the microfluidic chip 20. The ultrasonic transducer 72 typically applies vibrations to the reaction chamber 202a during cell lysis and nucleic acid washing to achieve ultrasonic lysis, promote cell separation, and promote mixing of reagents and magnetic beads, thus making the extraction process smoother and more efficient.
[0153] The magnetic adsorption device 8 is used to adsorb magnetic materials (such as magnetic beads) in the reaction chamber 202a of the microfluidic chip 20 to assist the extraction process.
[0154] The extraction process for the target analyte is generally divided into two stages: sample lysis and target analyte purification. Both processes are usually completed within reaction chamber 202a.
[0155] Sample lysis refers to the destruction of the sample's peripheral structure (such as the cell membrane) through some external effect, releasing target substances such as nucleic acids. The aforementioned release of reagents from storage chamber 201a into reaction chamber 202a in a predetermined order is a chemical lysis method, which achieves sample lysis through the reaction between chemical reagents. To improve lysis efficiency and effectiveness, in some embodiments, the detector 10 also includes an ultrasonic device 7 to achieve sample lysis using ultrasound. During operation, the ultrasonic transducer 72 of the ultrasonic device 7 contacts the outer wall of reaction chamber 202a, applying vibration to the reaction chamber 202a to cause cell lysis and release nucleic acids. Thus, with the cooperation of the rotary valve device 4 and the ultrasonic device 7, sample lysis can be achieved through a combination of ultrasound and chemical lysis, resulting in higher efficiency, better effects, and more efficient lysis to obtain more nucleic acids, thereby improving the success rate of nucleic acid detection.
[0156] After lysis, the target analyte often retains other components that inhibit amplification, such as proteins, polysaccharides, lipid macromolecules, and salts. Therefore, target analyte purification is necessary. Washing with a solution or similar medium separates the target analyte from other inhibitors, ultimately yielding a high-purity analyte. The washing process may need to be repeated several times, all within the reaction chamber 202a. During nucleic acid washing, the ultrasonic transducer 72 of the ultrasonic device 7 transmits ultrasonic vibrations to the reaction chamber 202a, which also mixes the reagents and magnetic beads, allowing for better adsorption of nucleic acids by the magnetic beads and more thorough removal of impurities.
[0157] After each washing, the waste liquid can be discharged, leaving the purified target substance in the reaction chamber 202a.
[0158] To prevent the target material obtained from lysis from being discharged with the waste liquid during the wastewater treatment process, in some embodiments, the storage chamber 201a stores magnetic materials such as magnetic beads, and during the extraction process, these magnetic materials are released into the reaction chamber 202a in a predetermined order. Magnetic beads are micron-sized particles with superparamagnetic properties. Under certain conditions, magnetic beads have a reversible adsorption capacity for target materials (including DNA and RNA); while other impurities such as proteins are not adsorbed by the magnetic beads and remain in the solution. Furthermore, releasing the eluent from the storage chamber 201a into the reaction chamber 202a to elute the magnetic beads and target material also allows the target material to detach from the magnetic beads, achieving separation of the target material and the magnetic beads, so that the purified target material can be transferred to the amplification chamber 205a for amplification without the magnetic beads.
[0159] In this case, to prevent the magnetic beads from being discharged from the reaction chamber 202a along with the liquid, in some embodiments, the detector 10 also includes a magnetic adsorption device 8 disposed on the base 1, which is used to separate the magnetic material and the liquid by adsorbing magnetic materials such as magnetic beads. This allows the magnetic adsorption device 8 to gather magnetic beads adsorbed with the target material during the sample lysis and target washing process, so as to separate the target material from the waste liquid and smoothly realize the target material lysis and purification process; on the other hand, during the target material elution and the transfer of the target material from the reaction chamber 202a to the amplification chamber 205a, the magnetic adsorption device 8 can also adsorb the magnetic beads that have detached from the target material, so as to separate the target material from the magnetic beads and smoothly realize the target material elution and the transfer of the target material from the reaction chamber 202a to the amplification chamber 205a.
[0160] The detection device 9 is used to detect the target analyte amplified in the amplification chamber 205a of the microfluidic chip 20. In some embodiments, the detection device 9 is a fluorescence detection device, which emits excitation light into the amplification chamber 205a through an optical fiber (not shown) to excite fluorescence, and recovers the excited fluorescence through the optical fiber so as to determine the presence and quantity of the target analyte based on the different intensities of the fluorescence generated in the amplification chamber 205a.
[0161] As can be seen, based on the cooperation of the holding device 2, the piercing device 3, the rotary valve device 4, the pump assembly 5, the temperature control device 6, the ultrasonic device 7, the magnetic suction device 8, and the detection device 9, the detector 10 can complete the extraction, amplification, and detection of target substances such as nucleic acids, and realize fully automatic control of the entire microfluidic detection process.
[0162] Of course, the detector 10 may also include only some of the holding device 2, puncture device 3, rotary valve device 4, pump assembly 5, temperature control device 6, ultrasonic device 7, magnetic suction device 8 and detection device 9 to achieve automatic control of part of the microfluidic detection process.
[0163] Figures 1 to 6The structure of the detector 10 in an embodiment of this application is illustrated by way of example. Figures 5 to 6 As shown, in this embodiment, the detector 10 includes a base 1, a holding device 2, a piercing device 3, a lifting mechanism 33, a linkage mechanism 36, a rotary valve device 4, a pump assembly 5, a temperature control device 6, an ultrasonic device 7, a magnetic suction device 8, and a detection device 9. The holding device 2, piercing device 3, lifting mechanism 33, linkage mechanism 36, rotary valve device 4, pump assembly 5, temperature control device 6, ultrasonic device 7, magnetic suction device 8, and detection device 9 are all mounted on the base 1. Furthermore, the connecting device 5a of the rotary valve device 4 and the pump assembly 5 is integrated into the piercing device 3, forming a fluid flow control device 103. Simultaneously, the fluid flow control device 103 and the lifting mechanism 33 together form an extraction device 102.
[0164] The base 1 is used to mount the holding device 2. The holding device 2 is used to mount the microfluidic chip 20.
[0165] The extraction device 102 is mounted on the base 1 and includes a fluid flow control device 103 and a lifting mechanism 33. The fluid flow control device 103 can move up and down between a highest point and a lowest point and includes at least one of a piercing element 32, a rotary valve, and a connecting nozzle 52. The piercing element 32 is used to drive the piercing needle 204c to approach the storage cavity 201a of the microfluidic chip 20 mounted on the holding device 2, piercing the sealing film on the storage cavity 201a. The rotary valve is used to connect to the rotor 203a of the switching valve 203 of the microfluidic chip 20, so as to drive the rotor 203a to rotate and realize the switching of the valve position of the switching valve 203. The connecting nozzle 52 is used to connect to the connecting port 204b of the microfluidic chip 20, so as to connect the connecting port 204b to the drive pump 51. The lifting mechanism 33 is driven to connect with the fluid control device 103 to drive the fluid control device 103 to move up and down relative to the base 1, so that the fluid control device 103 moves away from or closer to the microfluidic chip 20.
[0166] An ultrasonic device 7 is mounted on a base 1 and includes an ultrasonic transducer 72. The ultrasonic transducer 72 is located below the fluid flow control device 103 and can move vertically between a contact position and a clearance position below the contact position. In the contact position, the ultrasonic transducer 72 contacts the outer wall of the reaction chamber 202a of the microfluidic chip 20, transmitting vibrations to the reaction chamber 202a. In the clearance position, the ultrasonic transducer 72 is moved away from the reaction chamber 202a of the microfluidic chip 20.
[0167] The linkage mechanism 36 drives the extraction device 102 and the ultrasonic device 7, and converts the movement of the liquid flow control device 103 in the vertical direction Z into the movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position.
[0168] In the above scheme, since the linkage mechanism 36 links the extraction device 102 and the ultrasonic device 7, the movement of the fluid flow control device 103, including at least one of the piercing member 32, the rotary valve member, and the connecting nozzle 52, along the vertical direction Z under the drive of the lifting mechanism 33 is converted into the movement of the ultrasonic transducer 72 along the vertical direction Z between the contact position and the avoidance position. Therefore, at least one of the piercing member 32, the rotary valve member, and the connecting nozzle 52 and the ultrasonic device 7 are no longer independent of each other, but are linked together. This is beneficial to simplify the structure of the detector 10, reduce the volume of the detector 10, simplify the control process of the detector 10, realize further miniaturization and weight reduction of the detector 10, improve the ease of use of the detector 10, improve the working efficiency of the detector 10, and thus improve the performance of the detector 10.
[0169] In this design, the linkage mechanism 36 drives the extraction device 102 and the ultrasonic device 7, allowing the ultrasonic transducer 72 of the ultrasonic device 7 to move together with the fluid control device 103 of the extraction device 102, which includes at least one of the piercing element 32, the rotary valve element, and the connecting nozzle 52, under the drive of the lifting mechanism 33. This eliminates the need for a separate drive mechanism for the ultrasonic transducer 72. In other words, the ultrasonic drive mechanism in the related technology can be omitted, and the detector 10 no longer needs to include an ultrasonic drive mechanism. Therefore, this simplifies the structure of the detector 10, reduces its size and weight, further miniaturizes and lightens its weight, and improves its ease of use. In particular, since the fluid flow control device 103 and the ultrasonic device 7 are arranged vertically, the linkage mechanism 36 that enables their linkage occupies more vertical space and less horizontal space. Therefore, it is beneficial to reduce the floor area of the detector 10, which is of great significance for further miniaturization of the detector 10 and improving its ease of use. Moreover, the power for the fluid flow control device 103 and the ultrasonic device 7 to move in the vertical Z direction is provided by the lifting mechanism 33. The linkage mechanism 36 does not need to be equipped with a motor or other power mechanism. Compared with the ultrasonic drive mechanism in related technologies, it has a smaller floor area and lighter weight, which is also beneficial to further reduce the size and weight of the detector 10.
[0170] Meanwhile, since the linkage mechanism 36 enables linkage between at least one of the piercing element 32, the rotating valve element and the connecting nozzle 52 and the ultrasonic transducer 72 of the ultrasonic device 7, the ultrasonic transducer 72 can move along with at least one of the piercing element 32, the rotating valve element and the connecting nozzle 52 without separate control or additional time. Therefore, it also helps to simplify the control process, shorten the operation time and improve the working efficiency of the detector 10.
[0171] It can be seen that by setting up the linkage mechanism 36 to drive the extraction device 102 and the ultrasonic device 7, the movement of the liquid flow control device 103 in the vertical direction Z is converted into the movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position. This simplifies the structure of the detector 10, reduces the volume of the detector 10, simplifies the control process of the detector 10, further miniaturizes and lightens the detector 10, improves the ease of use of the detector 10, increases the working efficiency of the detector 10, and thus improves the performance of the detector 10.
[0172] In the above scheme, the linkage mechanism 36 realizes the linkage between the ultrasonic device 7 and at least one of the fluid flow control devices 103, including the piercing element 32, the rotary valve, and the connecting nozzle 52, rather than the linkage between the ultrasonic device 7 and other modules such as the temperature control device 6, the magnetic suction device 8, or the holding device 2. This has the advantage of simplifying the structure of the detector 10 and improving its working efficiency. This is because, compared to other modules of the detector 10 such as the temperature control device 6, the magnetic suction device 8, or the holding device 2, the movement state of the fluid flow control device 103, including at least one of the piercing element 32, the rotary valve, and the connecting nozzle 52, is more matched to the movement state of the ultrasonic device 7, less prone to conflict, and facilitates effective connection between different links. It also simplifies the structure of the linkage mechanism 36 that realizes the linkage between the two.
[0173] Specifically, during operation, the fluid flow control device 103, including at least one of the piercing element 32, the rotary valve, and the connecting nozzle 52, moves along the vertical direction Z. The ultrasonic transducer 72 of the ultrasonic device 7 also moves along the vertical direction Z. Furthermore, in a single operational phase (e.g., before extraction or amplification), both the fluid flow control device 103 and the ultrasonic transducer 72 only require unidirectional movement, without reciprocating motion. Therefore, their movements are consistent and their directions are aligned. Moreover, as mentioned earlier, the ultrasonic transducer 72 typically needs to be in contact during the extraction process, which occurs after the piercing element 32 pierces the sealing film of the microfluidic chip 20, the rotary valve connects to the rotor 203a of the microfluidic chip 20, and the connecting nozzle 52 connects to the connecting port 204b of the microfluidic chip 20. This means... This means that there is a coordinated relationship between the action of the ultrasonic transducer 72 and the actions of the piercing element 32, the rotary valve element and the connecting nozzle 52, and the timing is relatively well matched. All of this indicates that the motion state of the ultrasonic device 7 and the liquid flow control device 103 is well matched. Therefore, linking the two together will not easily cause action conflicts, and it is more convenient to effectively connect different links such as ultrasonic mixing and piercing, rotary valve and driving liquid flow. Therefore, it is beneficial to improve work efficiency. Moreover, in this case, the motion of the linkage mechanism 36 before and after the conversion is a movement along the vertical direction Z. The motion mode before and after the conversion is consistent. The linkage mechanism 36 does not need to make too many changes in the motion mode. For example, it can do little or no conversion between rotation and movement. Therefore, the structure of the linkage mechanism 36 is relatively simple, which is beneficial to simplify the structure of the detector 10.
[0174] Compared to the fluid flow control device 103, other modules such as the temperature control device 6, magnetic suction device 8, or holding device 2 either do not move vertically in the Z direction, or although they do move vertically in the Z direction, the timing or method of movement is mismatched. For example, in some embodiments, the temperature control device 6 and magnetic suction device 8 do not move vertically. Furthermore, in some embodiments, although the holding part 23 of the holding device 2 moves vertically, this movement is to enable the microfluidic chip 20 to switch between different temperature zones of the temperature control device 6. This movement occurs during the amplification process after the extraction process, and the movement is not a single... Instead of moving in the same direction, it moves up and down repeatedly, which is inconsistent with the timing and mode of movement of the ultrasonic transducer 72. This means that the matching degree between the temperature control device 6, the magnetic suction device 8 or the holding device 2 and other modules with the ultrasonic device 7 is low. Therefore, linking the temperature control device 6, the magnetic suction device 8 or the holding device 2 and other modules with the ultrasonic device 7 may easily cause action conflicts, or may require the linkage mechanism 36 to have a very complex structure, which may reduce the efficiency of the detector 10, increase the structural complexity of the detector 10, and result in the detector 10 being larger, heavier, and more expensive.
[0175] As can be seen, the linkage mechanism 36 utilizes the characteristic that the motion state between the fluid flow control device 103 of the extraction device 102, including the piercing member 32, the rotary valve member, and the connecting nozzle 52, and the ultrasonic transducer 72 of the ultrasonic device 7 is well matched, to link the extraction device 102 and the ultrasonic device 7. The movement of the fluid flow control device 103 along the vertical direction Z is converted into the movement of the ultrasonic transducer 72 of the ultrasonic device 7 along the vertical direction Z between the contact position and the avoidance position. This allows the detector 10 to achieve a more convenient and efficient microfluidic chip control process based on a simpler structure, smaller size, and lighter weight, effectively improving the performance of the detector 10.
[0176] In this application, the linkage mechanism 36 can convert the movement of the fluid flow control device 103 in the vertical direction Z into the movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position in various ways. For example, the unidirectional movement of the fluid flow control device 103 in the vertical direction Z (i.e., upward or downward movement) can be converted into the movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position. Alternatively, the bidirectional movement of the fluid flow control device 103 in the vertical direction Z (i.e., upward and downward movement) can be converted into the movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position. As another example, the movement of the fluid flow control device 103 in the vertical direction Z can be converted into the same-direction and / or opposite-direction movement of the ultrasonic transducer 72 in the vertical direction Z between the contact position and the avoidance position.
[0177] As a first example, in some embodiments, the linkage mechanism 36 converts the movement of the fluid flow control device 103 in the vertical direction Z into the same vertical direction Z movement of the ultrasonic transducer 72 between the contact position and the avoidance position. For example, in some embodiments, the linkage mechanism 36 converts the downward movement of the fluid flow control device 103 into the downward movement of the ultrasonic transducer 72, causing the ultrasonic transducer 72 to descend from the contact position to the avoidance position. In this way, before the fluid flow control device 103 moves downward and completes at least one of the actions such as puncture, switching valve connection, and communication port connection, the ultrasonic transducer 72 can be lowered to the avoidance position to provide space for placing the microfluidic chip 20 on the holding device 2, thus facilitating the smooth loading of the microfluidic chip 20.
[0178] In some embodiments, the linkage mechanism 36 converts the movement of the fluid flow control device 103 along the vertical direction Z into the reverse movement of the ultrasonic transducer 72 along the vertical direction Z between the contact position and the avoidance position. In this case, the linkage mechanism 36 performs reverse linkage between the fluid flow control device 103 and the ultrasonic transducer 72, converting the upward movement of the fluid flow control device 103 into the downward movement of the ultrasonic transducer 72 from the contact position to the avoidance position, and / or converting the downward movement of the fluid flow control device 103 into the upward movement of the ultrasonic transducer 72 from the avoidance position to the contact position. This is more conducive to providing sufficient space for the operation of other modules (e.g., the lifting and lowering of the holding part 23 of the holding device 2) and / or other operations (e.g., the placement of the microfluidic chip 20 on the holding part 23 of the holding device 2), making the entire detection process smoother.
[0179] For example, in some embodiments, during the downward movement of the fluid flow control device 103, the linkage mechanism 36 converts the downward movement of the fluid flow control device 103 into the upward movement of the ultrasonic transducer 72, so that the ultrasonic transducer 72 moves upward from the avoidance position to the contact position.
[0180] Based on the above scheme, the ultrasonic transducer 72 and the fluid control device 103 can be initially positioned in a clearance position and at their highest point, respectively. That is, the ultrasonic transducer 72 is in a clearance position before each detection begins, and the fluid control device 103 is at its highest point before each detection begins. At the start of each detection, the microfluidic chip 20 is first placed on the holding part 23 of the holding device 2, completing the chip loading. Since the ultrasonic transducer 72 is in a clearance position and the fluid control device 103 is at its highest point, both are away from the holding part 23 from the top and bottom. Therefore, there is sufficient space on both sides of the holding part 23, allowing the microfluidic chip 20 to be easily inserted, and the loading operation can be successfully achieved. After the chip loading is completed, the lifting mechanism 33 can be controlled to drive the fluid control device 103 downwards from its highest point, completing at least one of the actions such as puncturing, valve turning, and connecting the communication port 204b. During this process, under the action of the linkage mechanism 36... As the flow control device 103 descends, the ultrasonic transducer 72 moves upward from the avoidance position to the contact position. This ensures that the ultrasonic transducer 72 reaches the contact position when the flow control device 103 completes at least one of the puncture, valve turning, and connection port 204b, so that vibration can be applied to the reaction chamber 202a during the extraction process. In addition, if the detector 10 includes the aforementioned holding part 23 that drives the microfluidic chip 20 to switch between different temperature zones by moving up and down, the lifting mechanism 33 can be controlled to drive the flow control device 103 upward to the highest point before the amplification begins. The flow control device 103 then drives the ultrasonic transducer 72 downward from the contact position back to the avoidance position through the linkage mechanism 36. This allows both the flow control device 103 and the ultrasonic transducer 72 to move away from the holding part 23, leaving more space for the reciprocating up and down movement of the holding part 23, facilitating the reciprocating up and down movement of the holding part 23 between different temperature zones and smoothly realizing the amplification process.
[0181] It can be seen that the linkage mechanism 36 is configured such that during the downward movement of the liquid flow control device 103, the downward movement of the liquid flow control device 103 is converted into the upward movement of the ultrasonic transducer 72, so that the ultrasonic transducer 72 moves from the avoidance position to the contact position. This facilitates chip loading and also facilitates the reciprocating rise and fall of the holding part 23 during the amplification process to switch the temperature zone.
[0182] In some embodiments, during the process of the fluid flow control device 103 moving upward to the highest point, the linkage mechanism 36 converts the upward movement of the fluid flow control device 103 into the downward movement of the ultrasonic transducer 72, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position.
[0183] Based on the above scheme, the ultrasonic transducer 72 can be initially positioned in the contact position, and the fluid flow control device 103 can be initially positioned below the highest point. At the start of each test, the lifting mechanism 33 drives the fluid flow control device 103 upwards to the highest point. The fluid flow control device 103, through the linkage mechanism 36, then drives the ultrasonic transducer 72 downwards from the contact position to the avoidance position. This ensures that both the fluid flow control device 103 and the ultrasonic transducer 72 are away from the holding part 23, providing ample space for placing the microfluidic chip 20 on the holding part 23, facilitating the smooth installation of the microfluidic chip 20 onto the holding part 23 and achieving chip loading. Furthermore... In the case where the detector 10 includes the aforementioned holding part 23 that drives the microfluidic chip 20 to switch between different temperature zones by moving up and down, after extraction and before amplification begins, the lifting mechanism 33 can be controlled to drive the liquid flow control device 103 to move upward to the highest point. The liquid flow control device 103 then drives the ultrasonic transducer 72 to move downward from the contact position to the avoidance position through the linkage mechanism 36. This ensures that both the liquid flow control device 103 and the ultrasonic transducer 72 are far away from the holding part 23, leaving a large space for the reciprocating up and down movement of the holding part 23. This facilitates the reciprocating up and down movement of the holding part 23 between different temperature zones, thus smoothly realizing the amplification process.
[0184] It can be seen that the linkage mechanism 36 is configured such that during the process of the liquid flow control device 103 moving upward to the highest point, the upward movement of the liquid flow control device 103 is converted into the downward movement of the ultrasonic transducer 72, so that the ultrasonic transducer 72 moves downward from the contact position to the avoidance position. This not only facilitates chip loading, but also facilitates the reciprocating lifting and lowering of the holding part 23 during the extraction process to switch the temperature zone.
[0185] Although the aforementioned two reverse linkage methods—namely, "the linkage mechanism 36 converts the downward movement of the liquid flow control device 103 into the upward movement of the ultrasonic transducer 72 during the downward movement of the liquid flow control device 103, causing the ultrasonic transducer 72 to move upward from the avoidance position to the contact position," and "the linkage mechanism 36 converts the upward movement of the liquid flow control device 103 into the downward movement of the ultrasonic transducer 72 during the upward movement of the liquid flow control device 103 to its highest point, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position"—can both facilitate chip loading and temperature zone switching without affecting at least one of the following: sealing membrane puncture, switching valve connection, and communication port connection, as well as ultrasonic mixing. However, among these two methods, the one involving "the linkage mechanism 36 converting the downward movement of the liquid flow control device 103 into the upward movement of the ultrasonic transducer 72 during the downward movement of the liquid flow control device 103 into the upward movement of the ultrasonic transducer 72"—is less effective. Compared to the method of "moving the ultrasonic transducer 72 upward from the avoidance position to the contact position," the method of "the linkage mechanism 36 converting the upward movement of the liquid flow control device 103 into the downward movement of the ultrasonic transducer 72 during the process of the liquid flow control device 103 moving upward to the highest point, so that the ultrasonic transducer 72 moves downward from the contact position to the avoidance position" is more conducive to reducing the size of the detector 10. This is because, in this case, initially, the ultrasonic transducer 72 is in the contact position, and the liquid flow control device 103 is below the highest point. Both are closer to the holding part 23 in the vertical direction Z, occupying less space in the vertical direction. Thus, the overall height of the device is lower initially. In other words, when the device is not started, the overall height and size are smaller. Therefore, it is more conducive to reducing the size of the detector 10 and making the packaging and transportation of the device easier.
[0186] When the linkage mechanism 36 is configured such that "during the process of the fluid flow control device 103 moving upward to the highest point, the upward movement of the fluid flow control device 103 is converted into the downward movement of the ultrasonic transducer 72, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position", the movement of the ultrasonic transducer 72 from the contact position to the avoidance position is completed under the drive of the linkage mechanism 36. In this case, the reverse movement of the ultrasonic transducer 72, that is, the movement from the avoidance position to the contact position, can also be completed under the drive of the linkage mechanism 36, or it can be completed under the drive of the ultrasonic reset mechanism 73 mentioned below, instead of under the drive of the linkage mechanism 36.
[0187] Specifically, the movement of the ultrasonic transducer 72 from the contact position to the avoidance position, and from the avoidance position to the contact position, are both completed under the drive of the linkage mechanism 36. That is, when the bidirectional movement of the ultrasonic transducer 72 between the contact position and the avoidance position is completed under the drive of the linkage mechanism 36, the linkage mechanism 36 not only "converts the upward movement of the liquid flow control device 103 to the downward movement of the ultrasonic transducer 72 during the process of the liquid flow control device 103 moving upward to the highest point, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position," but also "converts the upward movement of the liquid flow control device 103 to the downward movement of the ultrasonic transducer 72 during the process of the liquid flow control device 103 moving upward to the highest point." During the downward movement from the highest point, the downward movement of the liquid flow control device 103 is converted into the upward movement of the ultrasonic transducer 72, causing the ultrasonic transducer 72 to return from the avoidance position to the contact position. In this case, the linkage mechanism 36 drives the connected extraction device 102 and the ultrasonic device 7 during both the upward movement of the liquid flow control device 103 towards the highest point and the downward movement from the highest point. Throughout the process, the linkage mechanism 36 performs bidirectional linkage between the liquid flow control device 103 and the ultrasonic device 7, realizing the reverse linkage between the liquid flow control device 103 and the ultrasonic transducer 72 in both the upward and downward directions.
[0188] When the ultrasonic transducer 72 moves only unidirectionally from the contact position to the avoidance position, driven by the linkage mechanism 36, but moves from the avoidance position to the contact position without being driven by the linkage mechanism 36, the linkage mechanism 36 only "converts the upward movement of the fluid flow control device 103 to the downward movement of the ultrasonic transducer 72 during the upward movement of the fluid flow control device 103 to the highest point, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position," and does not "convert the downward movement of the fluid flow control device 103 to the upward movement of the ultrasonic transducer 72 during the downward movement of the fluid flow control device 103 from the highest point, causing the ultrasonic transducer 72 to move downward from the avoidance position to the avoidance position." "Return to the contact position" In this case, the linkage mechanism 36 only drives the extraction device 102 and the ultrasonic device 7 during the upward movement of the liquid flow control device 103 towards the highest point. During the downward movement of the liquid flow control device 103 from the highest point, it no longer drives the extraction device 102 and the ultrasonic device 7, but instead drives the disconnection between the extraction device 102 and / or the ultrasonic device 7. Throughout the process, the linkage mechanism 36 only performs unidirectional linkage between the liquid flow control device 103 and the ultrasonic device 7, and only realizes the reverse linkage between the liquid flow control device 103 and the ultrasonic transducer 72 in the upward direction, but does not realize the linkage between the liquid flow control device 103 and the ultrasonic transducer 72 in the downward direction.
[0189] Furthermore, when the linkage mechanism 36 is configured to "convert the upward movement of the liquid flow control device 103 to the downward movement of the ultrasonic transducer 72 during the process of the liquid flow control device 103 moving upward to the highest point, causing the ultrasonic transducer 72 to move downward from the contact position to the avoidance position," the linkage mechanism 36 can continuously drive the connection between the extraction device 102 and the ultrasonic device 7 throughout the entire upward movement of the liquid flow control device 103 from the lowest point to the highest point, so that the ultrasonic transducer 72 continuously moves downward along with the liquid flow control device 103 throughout the entire upward movement of the liquid flow control device 103 from the lowest point to the highest point. Alternatively, the linkage mechanism 36 can also only... During the partial ascent of the liquid flow control device 103 from the lowest point to the highest point, it drives the extraction device 102 and the ultrasonic device 7. This causes the ultrasonic transducer 72 to descend only during the partial ascent of the liquid flow control device 103 from the lowest point to the highest point, while it does not descend during the other partial ascent of the liquid flow control device 103 from the lowest point to the highest point. The latter prevents the lifting mechanism 33 from continuously pulling the ultrasonic device 7 during the standby period of the detector 10, thus avoiding continuous heating of the lifting mechanism 33 and affecting its lifespan. Therefore, it is more conducive to improving the working reliability of the detector 10 and extending the lifespan of the detector 10.
[0190] In some embodiments, the linkage mechanism 36 is disconnectably driven to connect the extraction device 102 and / or the ultrasonic device 7. During the upward movement of the fluid flow control device 103 to its highest point, the linkage mechanism 36 drives the connection between the extraction device 102 and the ultrasonic device 7, converting the upward movement of the fluid flow control device 103 into a downward movement of the ultrasonic transducer 72, causing the ultrasonic transducer 72 to move downward from a contact position to a clearance position. During the downward movement of the fluid flow control device 103 from its highest point, the linkage mechanism 36 disconnects from the extraction device 102 and / or the ultrasonic device 7. Furthermore, an initial position is provided between the highest and lowest points. During the upward movement of the fluid flow control device 103 to its highest point, the linkage mechanism 36 only drives the connection between the extraction device 102 and the ultrasonic device 7 during the upward movement of the fluid flow control device 103 from its initial position to its highest point. During the upward movement of the fluid flow control device 103 from its lowest point to its initial position, the linkage mechanism 36 disconnects from the extraction device 102 and / or the ultrasonic device 7.
[0191] Based on the above scheme, the linkage mechanism 36 only drives the extraction device 102 and the ultrasonic device 7 during the upward movement of the liquid flow control device 103 towards the highest point. During the downward movement of the liquid flow control device 103 from the highest point, it no longer drives the extraction device 102 and the ultrasonic device 7, but instead disconnects from them. Throughout the process, the linkage mechanism 36 only performs unidirectional linkage between the liquid flow control device 103 and the ultrasonic device 7, achieving only the reverse linkage between the liquid flow control device 103 and the ultrasonic transducer 72 in the upward direction, and not the linkage between the liquid flow control device 103 and the ultrasonic transducer 72 in the downward direction. The advantage is that, on the one hand, the linkage mechanism 36 only needs to convert the upward movement of the liquid flow control device 103 into the downward movement of the ultrasonic transducer 72 from the contact position to the avoidance position, without needing to convert the downward movement of the liquid flow control device 103 into the upward movement of the ultrasonic transducer 72 from the avoidance position to the contact position. The linkage mechanism 36 does not need to operate continuously, thus extending the lifespan of the linkage mechanism. The lifespan is 36. On the other hand, when the flow control device 103 moves downward from the highest point to perform at least one of the puncture, valve turning, and connection port functions, it does not need to drive the ultrasonic transducer 72 to move. The two are less likely to interfere with each other, and it is more convenient for the flow control device 103 to perform the required functions and the ultrasonic mixing function to be realized smoothly. For example, when the flow control device 103 performs the resealing of the microfluidic chip 20 during the downward movement, since the resealing occurs after the extraction process, the flow control device 103 does not link with the ultrasonic device 7 during the downward movement from the highest point. This can effectively prevent the flow control device 103 from being obstructed by the ultrasonic transducer 72 when it moves downward from the position corresponding to at least one of the puncture, valve turning, and connection port functions toward the sealing position, thus affecting the smooth realization of the resealing function. Alternatively, the flow control device 103 may drive the ultrasonic transducer 72 to continue upward from the contact position, causing the ultrasonic transducer 72 to excessively press against the microfluidic chip 20, resulting in damage to the ultrasonic transducer 72 and / or the microfluidic chip 20.
[0192] Of course, when the flow control device 103 performs resealing of the microfluidic chip 20 during its downward movement, the linkage mechanism 36 can also be configured such that, during the process of the flow control device 103 moving downward from its highest point to a position corresponding to at least one of the puncture, rotary valve, and connecting port, it drives the connecting extraction device 102 and the ultrasonic device 7, converting the downward movement of the flow control device 103 into the upward movement of the ultrasonic transducer 72 from the avoidance position to the contact position, and at the position corresponding to at least one of the puncture, rotary valve, and connecting port... During the movement of the position toward the sealing position, the drive between the ultrasonic transducer 72 and the extraction device 102 and / or the ultrasonic device 7 is cut off to prevent mutual interference between the ultrasonic transducer 72 and the fluid flow control device 103 moving toward the sealing position. However, in this case, an additional separation mechanism is required, or the structure of the linkage mechanism 36 itself needs to be specially designed to achieve the drive cut-off between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7 at the position corresponding to at least one of the puncture, rotary valve and connecting port of the fluid flow control device 103. Therefore, the structure is relatively complex. The above solution directly constructs the linkage mechanism 36 so that it does not drive the extraction device 102 and the ultrasonic device 7 during the entire process of the liquid flow control device 103 moving downward. This eliminates the need for a separate separation mechanism or special design of the linkage mechanism 36 itself. The linkage mechanism 36 can achieve drive cut-off between the extraction device 102 and / or the ultrasonic device 7 at the position corresponding to at least one of the liquid flow control device 103 being punctured, rotating valve, and connecting port. This prevents mutual interference between the ultrasonic transducer 72 and the liquid flow control device 103 moving toward the sealing position. Therefore, the structure is relatively simple.
[0193] Furthermore, in the above-described scheme, when the linkage mechanism 36 converts the upward movement of the liquid flow control device 103 into the downward movement of the ultrasonic transducer 72 from the contact position to the avoidance position, it does not convert the upward movement of the liquid flow control device 103 from the lowest point to the highest point throughout the entire process of the liquid flow control device 103 moving upward into the ultrasonic transducer 72 moving downward into the avoidance position. Instead, it only converts the upward movement of the liquid flow control device 103 from the initial position between the lowest and highest points to the highest point into the downward movement of the ultrasonic transducer 72 moving downward into the avoidance position. In this case, the linkage mechanism 36 does not drive the connection between the extraction device 102 and the ultrasonic device 7 throughout the entire process of the liquid flow control device 103 moving from the lowest point to the highest point, but only during the process of the liquid flow control device 103 moving downward into the highest point. The lifting mechanism 33 only drives the extraction device 102 and the ultrasonic device 7 during the process of the liquid flow control device 103 rising from the initial position to the highest point. At this time, the initial position constitutes the dividing point for whether the linkage mechanism 36 drives the extraction device 102 and the ultrasonic device 7 during the rising process of the liquid flow control device 103. When the liquid flow control device 103 is in the initial position, the lifting mechanism 33 does not pull the ultrasonic transducer 72 through the linkage mechanism 36. In this way, the liquid flow control device 103 can be in the initial position during the standby process, thereby preventing the lifting mechanism 33 from being in the state of pulling the ultrasonic transducer 72 during the standby process, so as to avoid the lifting mechanism 33 from overheating due to continuous operation and affecting its lifespan. Therefore, it can effectively improve the working reliability of the detector 10 and extend the service life of the detector 10.
[0194] As can be seen, in the above scheme, the linkage mechanism 36 does not drive the extraction device 102 and the ultrasonic device 7 throughout the entire process of the liquid flow control device 103 rising and falling. Instead, it only drives the extraction device 102 and the ultrasonic device 7 during the process of the liquid flow control device 103 rising from the initial position to the highest point. It does not drive the extraction device 102 and the ultrasonic device 7 during the process of rising from the lowest point to the initial position and from the highest point to the lowest point. This non-full-process drive connection facilitates the smooth realization of at least one of the following based on a simpler structure: sealing membrane puncture, valve position switching, and connection of the communication port, ultrasonic mixing, chip loading, and temperature zone switching of the reciprocating rising and falling of the holding part 23. It also allows the extraction device 102 and the ultrasonic device 7 to disengage within a certain range (i.e., during the entire descent of the liquid flow control device 103 and during the rise of the liquid flow control device 103 from the lowest point to the initial position) without affecting each other.
[0195] In the foregoing embodiments, the linkage mechanism 36 can have various structural forms, such as at least one of a linkage mechanism, a cam mechanism, and a rack and pinion mechanism.
[0196] In addition, in the foregoing embodiments, in order to achieve a drive connection with the extraction device 102, the linkage mechanism 36 can be driven to connect with the liquid flow control device 103 or the lifting mechanism 33.
[0197] Furthermore, in embodiments where the linkage mechanism 36 is not continuously driving the extraction device 102 and the ultrasonic device 7, the linkage mechanism 36 can achieve driving connection or driving disconnection between the extraction device 102 and the ultrasonic device 7 by being detachably driving the connection with the extraction device 102 and / or the ultrasonic device 7. Moreover, when the linkage mechanism 36 is detachably driving the connection with the extraction device 102 and / or the ultrasonic device 7, the driving connection or driving disconnection between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7 can be achieved based on various structural forms.
[0198] For example, in some embodiments, the drive connection or drive disconnection between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7 is controlled by a separation mechanism. The separation mechanism drives the linkage mechanism 36 to contact or separate from the extraction device 102 and / or the ultrasonic device 7 to achieve the drive connection or drive disconnection between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7.
[0199] For example, in some other embodiments, the drive connection or disconnection between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7 is not controlled by the separation mechanism, but by the cooperative structure between the linkage mechanism 36 and the extraction device 102. The up-and-down movement of the liquid flow control device 103 allows the linkage mechanism 36 to contact or separate from the extraction device 102 and / or the ultrasonic device 7, thereby achieving the drive connection or disconnection between the linkage mechanism 36 and the extraction device 102 and / or the ultrasonic device 7. Since the separation mechanism can be omitted in this case, the structure is simpler and the control is more convenient.
[0200] The fluid flow control device 103 includes not only at least one of the piercing element 32, the rotary valve element, and the connecting nozzle 52, but also a support 31, which supports at least one of the piercing element 32, the rotary valve element, and the connecting nozzle 52, thereby enabling the driving connection between at least one of the piercing element 32, the rotary valve element, and the connecting nozzle 52 and the lifting mechanism 33.
[0201] The support 31 is particularly convenient when the fluid control device 103 includes at least two of the following: piercing element 32, rotary valve element, and connecting nozzle 52. This is because when the fluid control device 103 includes at least two of the following: piercing element 32, rotary valve element, and connecting nozzle 52, at least two of the following can be mounted on the support 31 and supported by the support 31, thus facilitating the integrated mounting of at least two of the following on the support 31.
[0202] In some embodiments, the detector 10 further includes an ultrasonic reset mechanism 73, which is connected to the ultrasonic device 7 and moves the ultrasonic transducer 72 from the avoidance position to the contact position during the downward movement of the liquid flow control device 103.
[0203] Since the ultrasonic reset mechanism 73 can move the ultrasonic transducer 72 from the avoidance position to the contact position during the downward movement of the liquid flow control device 103, the ultrasonic transducer 72 can move to the contact position during the downward movement of the liquid flow control device 103 to achieve at least one of the actions such as puncture, switching valve connection, and connecting port connection. This makes it convenient for the ultrasonic transducer 72 to apply vibration to the reaction chamber 202a during the extraction process.
[0204] Furthermore, since the ultrasonic reset mechanism 73 can move the ultrasonic transducer 72 from the avoidance position to the contact position during the downward movement of the liquid flow control device 103, the linkage mechanism 36 does not need to drive the connection between the ultrasonic device 7 and the extraction device 102 during the downward movement of the liquid flow control device 103. Therefore, the solution of setting the ultrasonic reset mechanism 73 is particularly suitable for the situation where the linkage mechanism 36 is disconnected from the ultrasonic device 7 and / or the extraction device 102 during the downward movement of the liquid flow control device 103.
[0205] When the movement of the ultrasonic transducer 72 from the avoidance position to the contact position is completed not by the linkage mechanism 36 and the extraction device 102, but only by the ultrasonic reset mechanism 73, it can not only prevent the ultrasonic transducer 72 from affecting the downward movement of the liquid flow control device 103, but also facilitate the use of the ultrasonic reset mechanism 73 to press the ultrasonic transducer 72 against the reaction chamber 202a after the ultrasonic transducer 72 reaches the contact position, so that the ultrasonic transducer 72 and the reaction chamber 202a maintain good contact during the extraction process and achieve a better ultrasonic vibration effect.
[0206] As an example of the ultrasonic reset mechanism 73, in some embodiments, the ultrasonic reset mechanism 73 includes an ultrasonic elastic element disposed on the base 1 and abutting against the lower part of the ultrasonic device 7. This elastic element applies an upward elastic force to the ultrasonic device 7 during the downward movement of the fluid flow control device 103, causing the ultrasonic transducer 72 to move upward from the avoidance position to the contact position. Based on this, under the action of the ultrasonic elastic element, the ultrasonic transducer 72 can automatically return to the contact position and contact the reaction chamber 202a during the downward movement of the fluid flow control device 103, which is convenient and efficient. Moreover, in this case, the maintenance of the ultrasonic transducer 72 in the contact position can be achieved solely by the ultrasonic elastic element, without relying on other mechanisms, resulting in a simpler structure. Furthermore, in this case, the pressure applied by the ultrasonic transducer 72 to the reaction chamber 202a can be controlled simply by pre-designing the specifications of the ultrasonic elastic element, eliminating the need for a dedicated ultrasonic detection device to detect the corresponding pressure, thus effectively simplifying the structure.
[0207] In some embodiments, to achieve stable positioning of the ultrasonic elastic element, the ultrasonic reset mechanism 73 includes a support shaft, on which the ultrasonic elastic element is sleeved. Thus, the support shaft can support the ultrasonic elastic element, thereby achieving stable positioning of the ultrasonic elastic element. Furthermore, the support shaft can guide the ultrasonic elastic element during its deformation along the vertical Z-direction, making it less prone to skew and allowing for more accurate extension and contraction along the vertical Z-direction. This facilitates more reliable driving of the ultrasonic transducer 72 back to the contact position.
[0208] When the ultrasonic reset mechanism 73 includes a support shaft, in some embodiments, the ultrasonic device 7 is movably mounted on the support shaft. This facilitates the ultrasonic device 7 to move up and down and return to the contact position when the ultrasonic elastic element unfolds along the support shaft and applies an elastic force to the ultrasonic device 7. Moreover, the support shaft can also guide the up and down movement of the ultrasonic device 7, making it easier for the ultrasonic transducer 72 to move up and down more accurately and reliably between the contact position and the avoidance position.
[0209] To facilitate the vertical movement of the ultrasonic device 7 on the support shaft, in some embodiments, the ultrasonic device 7 includes not only an ultrasonic transducer 72 but also an ultrasonic support 71. The ultrasonic transducer 72 is connected to the linkage mechanism 36 via the ultrasonic support 71, and the support shaft passes through the ultrasonic support 71, thus enabling the ultrasonic device 7 to move vertically on the support shaft. In this way, the linkage mechanism 36 can drive the ultrasonic transducer 72 to move vertically by driving the ultrasonic support 71 to slide along the support shaft, which is simple and convenient.
[0210] In the foregoing embodiments, the number of ultrasonic reset mechanisms 73 in the detector 10 can be one, two, or more. When the detector 10 includes at least two ultrasonic reset mechanisms 73, these at least two ultrasonic reset mechanisms 73 can be arranged at intervals in the horizontal direction to connect to different positions of the ultrasonic device 7. In this way, the ultrasonic device 7 can rise more smoothly from the avoidance position to the contact position, and after reaching the contact position, the ultrasonic device 7 can more tightly press against the reaction chamber 202a and apply vibration under the action of at least two ultrasonic reset mechanisms 73. Therefore, it is beneficial to achieve a better mixing effect.
[0211] For example, in some embodiments, the detector 10 includes three ultrasonic reset mechanisms 73 arranged in a triangle. Because the three ultrasonic reset mechanisms 73 are arranged in a triangle, the ultrasonic device 7 can be supported more stably and driven more smoothly to rise to the contact position. Furthermore, once at the contact position, the ultrasonic device 7 can more firmly press against the reaction chamber 202a and apply vibration under the action of the three ultrasonic reset mechanisms 73 arranged in a triangle, thus facilitating a better mixing effect.
[0212] As mentioned above, in the various embodiments of the application, the fluid flow control device 103 moves up and down between the highest and lowest points under the drive of the lifting mechanism 33. In some embodiments, the highest point is the position where the fluid flow control device 103 pulls the ultrasonic device 7 upward to the contact position through the linkage mechanism 36, and the lowest point is the sealing position. In some embodiments, the movement path of the fluid flow control device 103 also includes a piercing position and an initial position. The piercing position is lower than the highest point and higher than or level with the lowest point, and is the position where the piercing member 32 drives the piercing needle 204c to pierce the sealing film. The initial position is the position of the fluid flow control device 103 during standby. In some embodiments, it is also the dividing point between whether the linkage mechanism 36 drives the connection between the extraction device 102 and the ultrasonic device 7 during the upward movement of the fluid flow control device 103. It is located between the highest and lowest points, and specifically between the piercing position and the highest point.
[0213] The highest point, lowest point, initial position, and puncture position are the key positions during the lifting and lowering process of the fluid flow control device 103.
[0214] In the foregoing embodiments, the flow control device 103 includes at least one of the piercing element 32, the rotary valve element, and the connecting nozzle 52, which means that the flow control device 103 may include only one, two, or three of the piercing element 32, the rotary valve element, and the connecting nozzle 52.
[0215] When the fluid flow control device 103 includes three components—the piercing element 32, the rotary valve, and the connecting nozzle 52—it combines multiple functions such as piercing, rotary valve, and connecting nozzle connection, resulting in richer functionality. Furthermore, in this case, the piercing element 32, rotary valve, and connecting nozzle 52 can be integrated and driven by the same lifting mechanism 33, leading to a more compact structure, reduced number of driving mechanisms, simplified control process, and improved efficiency. Moreover, in this case, the linkage mechanism 36 links the fluid flow control device 103 and the ultrasonic device 7, enabling the ultrasonic device 7 to move along with the piercing element 32, rotary valve, and connecting nozzle 52, achieving a match between ultrasonic mixing and the three actions of piercing, rotary valve, and connecting nozzle connection. Therefore, it further enhances efficiency.
[0216] Regardless of whether the fluid flow control device 103 includes one, two, or three of the piercing element 32, the rotary valve, and the connecting nozzle 52, the fluid flow control device 103 can include at least the piercing element 32 so that the linkage mechanism 36 can at least link the piercing element 32 and the ultrasonic transducer 72. The advantage is that during movement, the piercing element 32 needs to break the connecting rib 204d between the piercing needle 204c and the top cover 204, causing the piercing needle 204c to detach from the top cover 204c. The force required for this breaking process is relatively large; therefore, it is typically used to drive the piercing needle... The lifting mechanism of the piercing element 32 has a large power, which means that when the fluid control device 103 includes the piercing element 32, the lifting mechanism 33 has a large power, which can effectively meet the needs of driving the ultrasonic transducer 72 to move without overloading, so as to avoid overloading the lifting mechanism 33 and affecting its lifespan, or that the lifting mechanism 33 has insufficient power and cannot drive the ultrasonic transducer 72 to the target position. In other words, when the fluid control device 103 includes the piercing element 32, the lifting mechanism 33 can drive the ultrasonic transducer 72 to move more safely and reliably.
[0217] The following mainly introduces the holding device 2 and the temperature control device 6.
[0218] like Figures 7 to 10 As shown, the holding device 2 is disposed on the base 1 and includes a holding part 23 and a holding drive part 22 that is driven to the holding part 23 to drive the holding part 23 to move up and down reciprocally. The holding part 23 is used to hold the microfluidic chip 20 and transport the microfluidic chip 20 to a position that cooperates with other modules so that other modules can apply an action to the microfluidic chip 20.
[0219] In this embodiment, the holding part 23 transports the microfluidic chip 20 primarily to cooperate with the temperature control device 6, which controls the temperature of the amplification cavity 205a of the microfluidic chip 20. During operation, the holding part 23 needs to move the microfluidic chip 20 up and down, so that the amplification cavity 205a of the microfluidic chip 20 is alternately inserted between the various temperature control units of the temperature control device 6, realizing the switching of the microfluidic chip 20 between different temperature zones, so that the amplification cavity 205a of the microfluidic chip 20 is controlled by different temperature zones.
[0220] In order to enable the microfluidic chip 20 to switch between different temperature zones, in this embodiment, the holding part 23 is movably arranged up and down. In this way, the holding part 23 can not only support and fix the microfluidic chip 20, but also drive the microfluidic chip 20 to rise and fall, so as to realize the rise and fall of the microfluidic chip 20 between different temperature control units of the temperature control device 6.
[0221] In addition, in this embodiment, the holding device 2 does not move horizontally. In this case, the holding part 23 does not drive the microfluidic chip 20 to move horizontally. The microfluidic chip 20 is not moved horizontally to remove the obstruction of the microfluidic chip picking and placing operation by other modules such as the flow control device 103 and the ultrasonic device 7. At the same time, the microfluidic chip 20 is not moved horizontally to achieve the approach and distance between the microfluidic chip 20 and the temperature control device 6.
[0222] This embodiment utilizes the reverse linkage between the flow control device 103 and the ultrasonic device 7 in the vertical Z direction to remove the obstruction of the microfluidic chip placement operation by the flow control device 103 and the ultrasonic device 7. Furthermore, in this embodiment, when the microfluidic chip 20 is placed on the holding part 23, its amplification cavity 205a is positioned horizontally between the temperature control units of the temperature control device 6, allowing direct insertion. Therefore, throughout the entire operation, the microfluidic chip 20 does not need to move horizontally closer to or further away from the temperature control device 6.
[0223] As can be seen, by setting up the linkage mechanism 36, the fluid flow control device 103 and the ultrasonic device 7 are linked in opposite directions in the vertical Z direction. During the upward process, the fluid flow control device 103 pulls the ultrasonic device 7 down to the avoidance position through the linkage mechanism 36. This also eliminates the need for the holding part 23 to move horizontally in order to transport the microfluidic chip 20. This eliminates the need for a drive mechanism to drive the holding part 23 to move horizontally. Therefore, from this perspective, it is also beneficial to simplify the structure, reduce the size, and improve efficiency.
[0224] In this embodiment, the holding part 23 includes a tray module, and the holding drive part 22 includes a holding lifting module. The tray module is used to support and position the microfluidic chip 20. It is connected to the base 1 by guide rail slider modules on both sides. The holding lifting module drives the tray module to move up and down, so that the microfluidic chip 20 and the temperature control device 6 can cooperate with each other.
[0225] The lifting module, which serves as the holding drive unit 22, includes a holding drive motor mounting plate 220, a gear 221, a rack mounting plate 222, a holding drive motor 223, and a rack 224.
[0226] The tray module serving as the holding part 23 includes: slider 230, guide rail 230a, tray body 231, tray limit block 232, tray positioning block 233, and spring 234.
[0227] like Figure 7 As shown, the base 1 includes a base plate 11, a first side plate 12, and a second side plate 13. The first side plate 12 and the second side plate 13 are connected to each other at both ends of the base plate 11 in the left-right direction Y and extend upward from the base plate 11.
[0228] The base 1 is provided with a mounting position 14, which is used to install the holding device 2. Specifically, the mounting position 14 is located on the first side plate 12 and the second side plate 13, at the lower part between the upper and lower ends of the first side plate 12 and the second side plate 13, and at the front part of the first side plate 12 and the second side plate 13.
[0229] The fixed drive motor mounting plate 220 is fixed to the base plate 11, the fixed drive motor 223 is fixed to the fixed drive motor mounting plate 220, and the rack 224 is fixed to the rack mounting plate 222. The gear 221 is driven to connect to the output shaft of the fixed drive motor 223 and meshes with the rack 224.
[0230] The tray body 231 and the left and right side tray limiting blocks 232 are the main structures for supporting the microfluidic chip 20. Guide rails 230a are fixed to both sides of the tray body 231, and sliders 230 on the left and right sides slide in cooperation with the guide rails 230a, respectively, and are fixed to the first side plate 12 and the second side plate 13 of the base 1. The tray module moves up and down through the relative sliding of the guide rails 230a and the sliders 230 in the vertical direction. The guide rails 230a are fixed to both sides of the rack and pinion fixing plate 222.
[0231] The rack fixing plate 222 is connected to the tray body 231. The fixed drive motor 223 drives the gear 221 to rotate, which drives the rack 224 to move in the vertical direction Z, thereby driving the tray module to move up and down in the vertical direction Z, and then driving the microfluidic chip 20 on the tray module to move up and down.
[0232] The left and right chip limiting blocks 232 guide the microfluidic chip 20 into the tray body 231 through the guide grooves 232a that can slide with the chip positioning part of the microfluidic chip 20.
[0233] When the microfluidic chip 20 is pushed into the tray module, it is first pushed from front to back into the space between the chip limiting blocks 232 on the left and right sides. The guide groove 232a on the inner side of the chip limiting block 232 contacts and abuts against the chip positioning part of the microfluidic chip 20 to prevent the microfluidic chip 20 from rotating or moving up and down. The chip positioning part includes, for example, a positioning block 202d (see reference). Figure 2 ).
[0234] During the process of pushing the microfluidic chip 20 into the tray module, the positioning block 202d presses down the chip positioning blocks 233 on the left and right sides. After the microfluidic chip 20 reaches the working position, the positioning block 202d does not contact the chip positioning blocks 233 on the left and right sides. The positioning blocks on the left and right sides will be bounced up by the spring 234 and pressed against the front of the positioning block 202d, thereby fixing and positioning the microfluidic chip 20.
[0235] The temperature control device 6 is fixed on the base 1 and located on the rear side of the holding device 2. It is used to control the temperature of the amplification chamber 205a of the microfluidic chip 20 on the holding part 23 of the holding device 2, so as to provide suitable and stable temperature conditions for the amplification reaction and enable the amplification reaction to proceed smoothly.
[0236] Figures 11 to 16 The structure of the temperature control device 6 is specifically shown. In this embodiment, the temperature control device 6 includes two temperature control units arranged side by side in the vertical direction Z, and each temperature control unit includes two temperature control modules 63 that are opposite to each other and can move relative to each other. The two temperature control modules 63 of the same temperature control unit move relative to each other, moving closer or further apart. When they move away from each other, the amplification element 205 of the microfluidic chip 20 is allowed to be inserted or withdrawn, and when they move closer together, the inserted amplification element 205 is clamped, thereby controlling the temperature of the amplification cavity 205a within the amplification element 205.
[0237] The two temperature control units correspond to different temperature ranges, forming upper and lower temperature zones to control the amplification chamber 205a at different temperature ranges. Specifically, in this embodiment, the upper temperature control unit corresponds to a temperature range of 90~100℃, and the lower temperature control unit corresponds to a temperature range of 50~60℃.
[0238] During operation, the holding part 23 drives the microfluidic chip 20 to move up and down repeatedly, causing the microfluidic chip 20 to continuously switch between the upper and lower temperature zones, performing multiple cycles of temperature control. Each complete switch between the lower and upper temperature zones constitutes one cycle, and a total of 40 to 50 (e.g., 45) cycles are performed during the amplification process.
[0239] like Figures 11 to 16 As shown, the temperature control device 6 includes a support frame 61, a heating element, a temperature control drive element 62, and a heat dissipation element 64. The two support frames 61 are respectively mounted on the first side plate 12 and the second side plate 13 of the base 1. The heating element, the temperature control drive element 62, and the heat dissipation element 64 are all mounted on the two support frames 61.
[0240] The heating element includes two temperature control units arranged vertically, each temperature control unit comprising two temperature control modules 63 arranged horizontally opposite each other, which can move closer or further apart. When the two temperature control modules 63 of the temperature control unit are far apart, they are in an open state; when they are close together, they are in a clamped state. For example, when the temperature control unit is not clamping the amplification section 205, the two temperature control modules 63 are in contact with each other. The temperature control units are used to heat the amplification chamber 205a of the microfluidic chip 20 to achieve nucleic acid amplification within the amplification chamber 205a. The two temperature control modules 63 of the upper temperature control unit form an upper temperature zone, the temperature of which is set between 90°C and 100°C. The two temperature control modules 63 of the lower temperature control unit form a lower temperature zone, the temperature of which is set between 50°C and 60°C.
[0241] The temperature control drive unit 62 is connected to the heating unit and is used to drive the temperature control unit to switch between the open state and the clamping state. The temperature control drive unit 62 is used to open the temperature control modules 63 on the left and right sides to allow the amplification component 205 of the microfluidic chip 20 to enter and clamp.
[0242] The heat dissipation unit 64 is used to continuously blow air to the lower temperature zone to reduce the temperature to 50°C.
[0243] The temperature control drive unit 62 includes a temperature zone fixing plate 620, a temperature control drive motor 621, a cam 622, a bearing 623, a linear bearing 624, a spring 625, a photoelectric switch baffle 626, a photoelectric switch 627, a pin 628, a temperature control drive motor fixing plate 629, and a movable shaft 6201.
[0244] The temperature-controlled drive motor mounting plate 629 is fixedly mounted relative to the support frame 61. The temperature-controlled drive motor 621 is mounted on the temperature-controlled drive motor mounting plate 629 and is located at the rear of the temperature-controlled drive motor mounting plate 629. The temperature-controlled drive motor mounting plate 629 has an opening in the middle, and the output shaft of the temperature-controlled drive motor 621 passes forward through the opening.
[0245] Four linear bearings 624 are arranged in two groups, left and right, in pairs. Each group of linear bearings 624 is mounted on two temperature zone fixing plates 620 arranged at intervals on the left and right sides. Two movable shafts 6201 are arranged in parallel and spaced apart. The axis of each movable shaft 6201 extends in the left-right direction Y and passes through the two linear bearings 624 on the left and right sides, so that the two temperature zone fixing plates 620 can move left and right along the two movable shafts 6201. Four springs 625 are arranged on the outside of the four linear bearings 624 to apply thrust to the temperature zone fixing plates 620 through the linear bearings 624.
[0246] Cam 622 is mounted on the output shaft of temperature control drive motor 621 and can rotate under the drive of the output shaft.
[0247] Bearing 623 is mounted on temperature zone fixing plate 620, and pin 628 is mounted on bearing 623. The axis of pin 628 extends in the front-rear direction. Two pins 628 are respectively located on the left and right sides of cam 622. Cam 622 applies thrust to temperature zone fixing plate 620 by pushing pin 628.
[0248] The photoelectric switch baffle 626 and photoelectric switch 627 are used together to detect whether the temperature control module 63 has moved into position when the temperature control unit switches to the open state.
[0249] Each temperature control module 63 is fixed on the corresponding temperature zone fixing plate 620. Driven by the temperature control drive motor 621 and pushed by the spring 625, the left and right temperature zone fixing plates 20 slide relative to each other on the movable shaft 6201, thereby driving the temperature control module 63 to move left and right.
[0250] Each temperature control module 63 in the heating section includes a heat-conducting block 630, a heat-insulating pad 631, and a heating element 632. Each temperature control module 63 is mounted on a temperature zone fixing plate 620 on the corresponding side. The heat-conducting blocks 630 of two temperature control modules 63 in the same temperature control unit are opposite each other. The heating element 632 is located between the heat-conducting block 630 and the heat-insulating pad 631. The heat-conducting block 630 is, for example, a heat-conducting aluminum block. The heat-insulating pad 631 is, for example, a bakelite pad.
[0251] The heat dissipation unit 64 includes a fan 640, a fixing component 641, and an air vent concentration block 642.
[0252] The fixing component 641 is connected to two support frames 61, and the air outlet concentrator 642 and the fan 640 are mounted on the fixing component 641. The fixing component 641 can be a single component that is simultaneously connected to both support frames 61, or it can include two components that are separately connected to the two support frames 61. The fixing component 641 is, for example, a sheet metal part.
[0253] A fan 640 is installed on each of the left and right sides of the heat dissipation unit 64, with the left and right fans 640 arranged roughly opposite each other. An air duct 642 is built into the air outlet block 642, which has two air inlets on the left and right sides and an air outlet on the front side, with the air outlet facing the lower temperature zone. The outlets of the two fans 640 are connected to the air inlets. The area of the air inlets is larger than the area of the air outlets, thereby increasing the airflow velocity at the outlets. The built-in air duct can be configured as a tapered or partially tapered section, i.e., it has a tapered flow channel. The axis of each fan 640 can gradually slope towards the lower temperature zone from the direction away from the air outlet block 642 to the direction closer to the air outlet block 642, to facilitate smoother fluid flow within the built-in air duct.
[0254] The temperature control drive motor 621 drives the cam 622 to rotate approximately 45°, bringing the larger diameter of the cam 622 closer to horizontal. This pushes the temperature control modules 63 on both sides of the temperature control unit apart, switching the temperature control unit to the open state. After the amplification component 205 of the microfluidic chip 20 is placed in the gap between the two temperature control modules 63, the temperature control drive motor 621 drives the cam 622 to rotate approximately 45° again, bringing the smaller diameter of the cam 622 closer to horizontal. The temperature control modules 63 on both sides are pushed back to their original position by the springs 625 on both sides, clamping the amplification component 205.
[0255] The temperature control module 63 heats the amplification chamber 205a via the heating element 632, and then the heat is transferred to the amplification chamber 205a by the heat-conducting block 630 to achieve temperature control of the amplification chamber 205a. The temperature control module 63 has a built-in temperature sensor to monitor temperature changes.
[0256] When the temperature control unit switches from the clamping state to the open state, the photoelectric switch 627 detects that the right temperature control module 63 is in place, and the temperature control drive motor 621 stops driving, waiting for the microfluidic chip 20 to be placed. After the amplification component 205 of the microfluidic chip 20 enters the heating section, the temperature control drive motor 621 drives the cam 622 to rotate, causing the temperature control unit to switch from the open state to the clamping state. Under the action of the spring 625, the left and right temperature control modules 63 clamp the amplification component 205 and the heating section begins to heat and amplify. The amplification cavity 205a first enters the lower temperature zone for heating and amplification, and then enters the upper temperature zone for heating and amplification. The switching between the lower temperature zone and the upper temperature zone is one cycle, and the temperature zone switching is repeated 45 times.
[0257] When switching temperature zones, the temperature control unit is turned on, and the holding part 23 is driven up and down by the holding drive part 22 of the holding device 2 to move to the temperature zone to be reached by the expansion component 205.
[0258] The detection fiber 901 is used to transmit the acquired optical signal from the amplification cavity 205a to the detection device.
[0259] like Figure 5 and Figure 6As shown, after the holding device 2 is installed on the mounting position 14, the holding device 2 is in a lower and forward position, which can leave sufficient space for the liquid flow control device 103 and ultrasonic device 7 located on the upper and lower sides, as well as the temperature control device 6 and detection device 9 located at the rear, so as to facilitate the installation of the liquid flow control device 103, ultrasonic device 7, temperature control device 6 and detection device 9, and facilitate their cooperation with the liquid flow control device 103, ultrasonic device 7, temperature control device 6 and detection device 9.
[0260] In this configuration, the linkage mechanism 36 pulls the ultrasonic device 7 down to a clearance position when the fluid control device 103 rises from its initial position to its highest point. This allows for clearance during the placement of the microfluidic chip 20 and the raising and lowering of the holding part 23. In this situation, when the fluid control device 103 is at its highest point and the ultrasonic device 7 is in the clearance position, both are at their furthest point from the holding part 23. This provides ample space on both the upper and lower sides of the holding part 23, preventing it from being obstructed by the fluid control device 103 and the ultrasonic device 7. Therefore, in this state, the microfluidic chip 20 can be easily placed on the holding part 23, successfully completing the installation and fixation of the microfluidic chip 20 on the holding part 23. Furthermore, the holding part 23 can be raised and lowered repeatedly as needed to facilitate temperature zone switching during the amplification process. In view of this, at the beginning of the detection, the lifting mechanism 33 can be controlled to drive the fluid control device 103 to rise from the initial position to the highest point, and the ultrasonic device 7 can be pulled down from the contact position to the avoidance position through the linkage mechanism 36. Then, the microfluidic chip 20 can be installed on the holding part 23. After that, after the extraction is completed and before the amplification begins, the lifting mechanism 33 can be controlled to drive the fluid control device 103 back to the highest point, and the ultrasonic device 7 can be pulled down from the contact position to the avoidance position again through the two linkage mechanisms 36a, so as to prevent the ultrasonic transducer 72 and the fluid control device 103 from affecting the reciprocating lifting of the holding part 23 during the subsequent amplification process.
[0261] Furthermore, since the movement of the ultrasonic device 7 from the contact position to the avoidance position is driven by the lifting mechanism 33 of the liquid flow control device 103 under the action of the linkage mechanism 36, the descent process of the ultrasonic device 7 and the lifting process of the liquid flow control device 103 are driven by the same lifting mechanism 33. This eliminates the need for a driving mechanism to drive the ultrasonic device to descend. Therefore, the structure is simpler, the size is smaller, the weight is lighter, the control is more convenient, and the efficiency is higher.
[0262] Furthermore, during the process of the liquid flow control device 103 descending from the highest point to the lowest point, the linkage mechanism 36 releases the linkage between the liquid flow control device 103 and the ultrasonic device 7. The advantage is that the liquid flow control device 103 can easily descend to the puncture position and the lowest point to perform operations such as puncture, valve rotation, connection of the connecting port, and resealing, without being restricted by the ultrasonic device 7. In particular, the movement of the liquid flow control device 103 from the puncture position to the lowest point is not restricted by the ultrasonic device 7, making it simpler and more convenient. Moreover, the ultrasonic device 7 can return to the contact position before the liquid flow control device 103 reaches the puncture position, i.e., under the action of the ultrasonic reset mechanism 73. This allows the vibration excitation required for the extraction process to be applied at any time after puncture, valve rotation, and connection of the connecting port, and the corresponding movement back to the contact position is not affected by the descent action of the liquid flow control device 103, making it simpler and more convenient.
[0263] Setting an initial position between the highest and lowest points and configuring it as the dividing point for whether the linkage mechanism 36 drives the flow control device 103 and the ultrasonic device 7 during the rising process of the flow control device 103 has the advantage that, during standby, the flow control device 103 does not need to pull the ultrasonic device 7, and the lifting mechanism 33 of the flow control device 103 does not need to work continuously. Therefore, it can effectively prevent the lifting motor of the lifting mechanism 33 from overheating during standby, which would affect its lifespan.
[0264] Moreover, in this embodiment, the fluid flow control device 103 includes a piercing member 32. The lifting motor not only drives the fluid flow control device 103 to lift as a whole, but also drives the piercing member 32 to break the connecting rib 204d. It has a large power, so the lifting mechanism 33 can effectively meet the pull-down requirements of the ultrasonic device 7, which is safe and reliable.
[0265] In summary, the detector 10 of this embodiment integrates multiple functional modules such as the holding device 2, the piercing device 3, the rotary valve device 4, the pump assembly 5, the temperature control device 6, the ultrasonic device 7, the magnetic suction device 8, and the detection device 9, which can realize fully automated control of the entire nucleic acid detection process. Moreover, since the rotary valve device 4 and the connecting device 5a are both integrated on the piercing device 3 and driven by the same lifting mechanism 33, and the lifting mechanism 33 also drives the ultrasonic device 7 to descend from the contact position to the avoidance position through the linkage mechanism 36, the structure is simple, the layout is compact, the size is small, the weight is light, and the efficiency is high.
[0266] The detector 10 in this embodiment is easy to use and requires minimal operator skill. Operators only need to perform the following three steps to conduct fully automated, end-to-end testing:
[0267] (1) Add the sample to the microfluidic chip 20;
[0268] (2) Place the microfluidic chip 20 on the holding part 23 of the holding device 2;
[0269] (3) After the test is completed, remove the microfluidic chip 20.
[0270] Specifically, the working process of the detector 10 in this embodiment mainly includes four steps: microfluidic chip loading, nucleic acid extraction, nucleic acid amplification and detection, and microfluidic chip removal.
[0271] The microfluidic chip loading step mainly includes: driving the lifting mechanism 33 to raise the fluid control device 103, which includes the piercing device 3, the rotary valve device 4 and the connecting device 5a, from the initial position to the highest point; at the same time, pulling the ultrasonic device 7 down from the contact position to the avoidance position through the linkage mechanism 36; and then, the operator installs the microfluidic chip 20 on the holding part 23 of the holding device 2 to complete the loading of the microfluidic chip 20.
[0272] The nucleic acid extraction process mainly includes the following steps:
[0273] (1) After the microfluidic chip 20 is loaded, the lifting motor of the lifting mechanism 33 is rotated in the opposite direction to drive the liquid flow control device 103, which includes the piercing device 3, the rotary valve device 4 and the connecting device 5a, to move downward from the highest point, so that the liquid flow control device 103 reaches the piercing position. The piercing part 32 crushes the connecting rib 204d between the connecting top cover 204 of the microfluidic chip 20 and the piercing needle 204c, so that the piercing needle 204c falls down and pierces the sealing film on the storage cavity 201a of the microfluidic chip 20, so that the storage cavity 201a containing the reagent is connected to the atmosphere.
[0274] (2) After the connecting rib 204d is broken, the piercing part 32 continues to move downward until the rotary valve shaft on the piercing device 3 is fitted onto the valve stem 203b of the microfluidic chip 20, and the connecting nozzle 52 on the piercing device 3 is inserted into the connecting port 204b of the microfluidic chip 20. After connecting the microfluidic chip 20 with the drive pump 51, the downward movement is paused, and the rotary valve motor of the rotary valve device 4 works, driving the rotary valve shaft to rotate the valve stem 203b according to a specific timing and angle, so that different storage chambers 201a are switched to connect with the reaction chamber 202a. When the storage chamber 201a is connected to the reaction chamber 202a, the fluid in the storage chamber 201a is pumped into the reaction chamber 202a by the suction action of the drive pump 51. During the connection process between the rotary valve shaft and valve stem 203b, and between the connecting nozzle 52 and the connecting port 204b, although the piercing member 32 presses on the annular member 204h, causing the rib 204f between the annular member 204h and the stop member 204e to deform to a certain extent, it does not completely break the rib 204f connecting the annular member 204h and the stop member 204e. Therefore, the stop member 204e still prevents the piercing needle 204c from moving further down, so that the piercing needle 204c can be kept at the position of piercing the sealing film and connecting the storage cavity 201a with the atmosphere. At the same time, the stop member 204e does not cause the piercing member 32 to be completely unable to move down, but the deformation of the rib 204f meets the corresponding downward movement requirements of the piercing member 32.
[0275] (3) When the lifting mechanism 33 drives the liquid flow control device 103, which includes the piercing device 3, the rotary valve device 4 and the connecting device 5a, to move downward from the highest point, the linkage mechanism 36 no longer drives the connection between the liquid flow control device 103 and the ultrasonic device 7. The ultrasonic transducer 72 of the ultrasonic device 7 then returns to the contact position under the action of the ultrasonic reset mechanism 73, and presses against the outer wall of the reaction chamber 202. During the reaction process, when the magnetic beads and reagents in the reaction chamber 202a need to be mixed, vibration is applied to the outer wall of the reaction chamber 202 to mix the magnetic beads and reagents to assist in nucleic acid extraction.
[0276] (4) During the reaction, when the magnetic beads and reagents are mixed and the waste liquid needs to be discharged, the magnet 81 of the magnetic adsorption device 8 is rotated to the magnetic adsorption position and contacts the reaction chamber 202a, adsorbing the magnetic beads onto the inner wall of the reaction chamber 202a. Then, under the squeezing action of the drive pump 51, the waste liquid is discharged to the outside of the reaction chamber 202a.
[0277] (5) After nucleic acid extraction is completed under the synergistic action of the flow control device 103, ultrasonic device 7, magnetic suction device 8, drive pump 51, lifting mechanism 33, linkage mechanism 36 and ultrasonic reset mechanism 73, firstly, the rotary valve motor works to drive the valve rod 203b to rotate, connecting the reaction chamber 202a and the amplification chamber 205a. Under the squeezing action of the drive pump 51, the nucleic acid extraction liquid flows into the amplification chamber 205a. After that, the flow control device 103 continues to move down to the lowest point. During the corresponding process, the piercing part 32 breaks the rib 204f of the microfluidic chip 20, so that the piercing needle 204c of the microfluidic chip 20 and the cover plate 26 together reseal the storage chamber 201a, preparing for amplification and fluorescence detection.
[0278] During the process of the nucleic acid extraction solution flowing into the amplification chamber 205a and the storage chamber 201a being resealed by the piercing needle 204c and the cover plate 206, the rotary valve shaft and the connecting nozzle 52 continue to move downwards along with the piercing device 3. During this downward movement, the rotary valve shaft and the connecting nozzle 52 will not be damaged. The connecting nozzle 52 can move moderately up and down under the action of the constraint member 55 to prevent damage, while the rotary valve shaft can be strengthened by using higher-strength materials to prevent damage. Furthermore, since the liquid transfer steps in the entire detection process have been completed during this downward movement, even if the continued downward movement of the rotary valve shaft and the connecting nozzle 52 causes damage to the switching valve 203 and the connecting port 204b of the microfluidic chip 20, it will not affect the subsequent processes, and the entire detection process can still be completed smoothly. In fact, it is desirable that the rotary valve shaft and the connecting nozzle 52 cause damage to the switching valve 203 and the connecting port 204b during the corresponding downward movement. This is because it prevents the microfluidic chip 20 from being reused without affecting the smooth completion of the detection, thus avoiding problems caused by the reuse of the microfluidic chip 20.
[0279] (6) After the resealing operation is completed, the lifting mechanism 33 drives the liquid flow control device 103 to return from the lowest point to the highest point. During the process of rising from the initial position to the highest point, the ultrasonic device 7 is pulled down from the contact position to the avoidance position again through the linkage mechanism 36 so that during the amplification process, the holding drive part 22 drives the holding part 23 to move up and down to switch the temperature zone.
[0280] The main steps of nucleic acid amplification and detection include the following processes:
[0281] (1) After the liquid flow control device 103 returns to the highest point, the holding part 23 moves up and down, driving the microfluidic chip 20 to move between the two temperature control units of the temperature control device 6. The two temperature control units control the temperature in different temperature ranges. The chip stays at the lower temperature control unit for a certain period of time (e.g., 10s) and is heated in the range of 50~60°. Then, the holding part 23 drives the microfluidic chip 20 to rise to the upper temperature control unit and stays there for a certain period of time (e.g., 4~5s) and is heated in the range of 90~100°. Then, the holding part 23 drives the microfluidic chip 20 back to the lower temperature control unit. This process is repeated for about 45 cycles to complete the amplification process. During this process, since the liquid flow control device 103 is at the highest point and the ultrasonic device 7 is in a clearance position, the two will not affect the rise and fall of the holding part 23.
[0282] (2) During amplification, the detection device 9 works, repeatedly switching the fluorescence detection channel to detect the excited fluorescence in the amplification chamber 205a in real time;
[0283] (3) After amplification and detection are completed, a detection report is generated and the detection record is stored.
[0284] The microfluidic chip 20 removal process mainly includes the following two steps:
[0285] (1) After the test is completed, the microfluidic chip 20 is removed from the holding part 23. During the process, since the liquid flow control device 103 is at the highest point and the ultrasonic device 7 is in the avoidance position, the holding part 23 does not need to be moved horizontally, and the operator can easily remove the microfluidic chip 20 from the holding part 23.
[0286] (2) After removing the microfluidic chip 20, the operator takes out the microfluidic chip 20 and puts it into a specific collection box for further processing. If it is necessary to continue testing a second sample, the above steps are repeated. If it is not necessary to continue testing, the lifting mechanism 33 drives the liquid flow control device 103 to descend to the initial position. During the process, the ultrasonic device 7 also rises to the contact position under the action of the ultrasonic reset mechanism 73. At this time, the instrument sends a signal that it can be powered off. When the operator powers off the instrument, the detector 10 is turned off.
[0287] In each of the above steps, the actions of each component of the detector 10 can be completed under the control of the controller of the detector 10.
[0288] It is evident that the detector 10 in this embodiment has advantages such as high integration, automation, and wide application range, which is conducive to promoting rapid on-site nucleic acid testing.
[0289] The above description is merely an exemplary embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A temperature control device (6) for controlling the temperature of the amplification chamber (205a) of the amplification element (205) of a microfluidic chip (20), characterized in that, include: A temperature control unit, two or more of the temperature control units are configured to control the amplification chamber (205a) to have different temperatures. The temperature control unit includes two temperature control modules (63) arranged opposite to each other. The temperature control unit has an open state and a clamping state. In the open state, the two temperature control modules (63) are moved away from each other so that the amplification element (205) enters the gap between the two temperature control modules (63). In the clamping state, the two temperature control modules (63) are moved closer to each other so that the amplification element (205) is clamped in the gap between the two temperature control modules (63). and Temperature control drive unit (62) is connected to the temperature control unit to control the temperature control unit to switch between the open state and the clamping state.
2. The temperature control device (6) according to claim 1, characterized in that, The temperature control drive unit (62) is configured to drive the two temperature control modules (63) of the temperature control unit to move synchronously in opposite directions; and / or The temperature control drive unit (62) is configured to control the two or more temperature control units to switch synchronously between the open state and the clamping state.
3. The temperature control device (6) according to claim 1, characterized in that, The temperature control unit includes: A heat-conducting block (630) includes a heat exchange surface, which is used to fit against the amplification element (205) in the clamped state to control the temperature of the amplification cavity (205a) of the amplification element (205); A heat insulation pad (631) is disposed on the side of the heat-conducting block (630) away from the heat exchange surface; and A heating element (632) is disposed between the heat-conducting block (630) and the heat-insulating pad (631).
4. The temperature control device (6) according to claim 1, characterized in that, The temperature control drive unit (62) includes: A separation drive mechanism is configured to apply a first force to the two temperature control modules (63) to move them apart from each other in order to control the temperature control units to switch from the clamped state to the open state and to release the first force; and The reset drive mechanism is configured to apply a second force to the two temperature control modules (63) to bring them closer together, so as to control the temperature control unit to switch from the open state to the clamping state when the separation drive mechanism releases the first force.
5. The temperature control device (6) according to claim 4, characterized in that, The separation drive mechanism includes: Temperature zone fixing plate (620), the two temperature control modules (63) of the temperature control unit are respectively disposed on the two temperature zone fixing plates (620) that are relatively spaced apart; Temperature-controlled drive motor (621); and The cam (622) is driven to rotate under the drive of the temperature control drive motor (621). The cam (622) is drivably engaged with the two temperature zone fixing plates (620). The cam (622) drives the two temperature zone fixing plates (620) and the two temperature control modules (63) on them to move closer or further away from each other to apply the first force to the two temperature control modules (63) and release the first force.
6. The temperature control device (6) according to claim 5, characterized in that, The separation drive mechanism further includes: Bearing (623), disposed on the temperature zone fixing plate (620); and Pin (628) is supported on bearing (623). Cam (622) abuts against pin (628) so that pin (628) drives the two temperature zone fixing plates (620) and the two temperature control modules (63) on them to move closer or further apart.
7. The temperature control device (6) according to claim 5, characterized in that, The separation drive mechanism further includes: A linear bearing (624) is mounted on the temperature zone fixing plate (620); and The movable shaft (6201), supported on the linear bearing (624), is configured to guide the two temperature zone fixing plates (620) and the two temperature control modules (63) on them to move closer or further apart.
8. The temperature control device (6) according to claim 4, characterized in that, The temperature control drive unit (62) further includes a position detection device, which is configured to detect whether the temperature control module (63) has reached the preset position required by the temperature control unit in the open state. The separation drive mechanism is coupled to the position detection device and is configured to stop operating if the detection result of the position detection device is yes during the process of switching the temperature control unit from the clamping state to the open state.
9. The temperature control device (6) according to claim 5, characterized in that, The reset drive mechanism includes a spring (625) configured to apply a force to the temperature zone fixing plate (620) toward the temperature control module (63) disposed thereon to apply the second force to the temperature control module (63).
10. The temperature control device (6) according to any one of claims 1 to 9, characterized in that, It also includes a heat dissipation unit (64) configured to reduce the temperature of the temperature control unit that forms a lower temperature zone in the two or more temperature control units.
11. The temperature control device (6) according to claim 10, characterized in that, The heat dissipation unit (64) includes: Fan (640); and The air outlet concentration block (642) has a built-in air duct (642a) with an air inlet and an air outlet. The air inlet is connected to the outlet of the fan (640), and the air outlet is opposite to the two temperature control modules (63) of the temperature control unit that forms the lower temperature zone.
12. The temperature control device (6) according to claim 11, characterized in that, The heat dissipation unit (64) includes two or more fans (640), and the built-in air duct (642a) has two or more air inlets corresponding one-to-one with the two or more fans (640); and / or The built-in air duct (642a) has a tapered flow channel section.
13. An amplification device, characterized in that, include: The temperature control device (6) according to any one of claims 1 to 12; and The holding device (2) includes a holding part (23) for holding the microfluidic chip (20), the holding part (23) being variably positioned so that the amplification part (205) of the microfluidic chip (20) moves between different temperature control units when the two or more temperature control units are in the open state.
14. A detector (10), characterized in that, Includes the amplification device as described in claim 13.
15. A detection system (100), characterized in that, include: A microfluidic chip (20) includes an amplification element (205) having an amplification cavity (205a); and The detector (10) as described in claim 14.