Detector and detection system
Patent Information
- Application Number
- CN202210459932.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-04-28
- Publication Date
- 2026-10-27
- Estimated Expiration
- 2042-04-28
AI Technical Summary
相关技术中的检测仪,性能仍有待改善
[0050]在本申请中,由于拨开机构能够在微流控芯片的待温控部位开始从两个温控模块之间向外移动之前,将两个温控模块分开,因此,可以减小待温控部位在移出过程中与两个温控模块的摩擦,降低待温控部位因移出过程中与两个温控模块摩擦而受到损害的风险。可见,本申请可以有效改善检测仪的性能,使得检测仪能够更加安全可靠地对微流控芯片进行操控。
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Figure CN117004486B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of microfluidic detection technology, and in particular to a detector and detection system. Background Technology
[0002] A microfluidic chip is a microfluidic chip that integrates multiple experimental steps. It is generally equipped with tiny channels and chambers arranged in a certain pattern. Different reagents are released in a certain order and flow into the designated chambers through different channels to complete the designated biochemical reactions, so as to achieve the purpose of sample preparation and detection.
[0003] The detector is used to automate the manipulation of microfluidic chips to control the preparation and detection of target substances such as nucleic acids. However, the performance of detectors in related technologies still needs improvement. Summary of the Invention
[0004] One of the technical problems that this application aims to solve is: improving the performance of the detector.
[0005] To address the aforementioned technical problems, this application provides a detector, comprising:
[0006] Base;
[0007] A holding device is disposed on the base and used to hold the microfluidic chip;
[0008] A temperature control device, mounted on a base, includes two temperature control modules positioned opposite each other and movable relative to each other. When the portion of the microfluidic chip to be temperature-controlled is inserted between the two temperature control modules, the module controls the temperature of that portion.
[0009] The disengaging mechanism is movably positioned relative to the retaining device, and separates the two temperature control modules before the part to be temperature controlled begins to move outward from between the two temperature control modules, so that the part to be temperature controlled can move outward from between the two temperature control modules.
[0010] In some embodiments, the temperature control device includes two opening members, which are connected to two temperature control modules in a one-to-one correspondence. The disengaging mechanism separates the two temperature control modules by pushing the two opening members away from each other.
[0011] In some embodiments, the opening element includes a protrusion, and the disengaging mechanism pushes two opening mechanisms away from each other by acting on the protrusion.
[0012] In some embodiments, the surface of the opening member that contacts the disengaging mechanism is arc-shaped.
[0013] In some embodiments, the temperature control device includes a reset elastic member that abuts against an opening member and applies an elastic force to the opening member to bring the two opening members closer together.
[0014] In some embodiments, the separating mechanism includes a separating element that is rotatably disposed, and the separating mechanism separates the two temperature control modules by means of the separating element.
[0015] In some embodiments, the disengaging mechanism is movably disposed relative to the retaining device, and the disengaging mechanism separates the two temperature control modules during the vertical movement.
[0016] In some embodiments, the holding device includes a holding member with a positioning block for engaging with the positioning slot of the microfluidic chip to fix the microfluidic chip.
[0017] In some embodiments, the detector includes a limiting member for insertion into a slot of the microfluidic chip to press the microfluidic chip in place.
[0018] In some embodiments, a limiting member is provided on the temperature control device so as to insert the microfluidic chip into the slot during the process of inserting two temperature control modules into the part to be temperature controlled.
[0019] In some embodiments, the limiting member is provided with a correction block, the width of which gradually decreases along the direction in which the limiting member is inserted into the slot.
[0020] In some embodiments, the holding device is horizontally movable relative to the base, and the detector includes a holding drive mechanism that is driven to the holding device to drive the holding device to move horizontally toward or away from the temperature control device.
[0021] In some embodiments, the detector includes:
[0022] The puncture device includes a puncture mechanism and a puncture drive mechanism that are driven together. The puncture drive mechanism drives the puncture mechanism to move relative to the base. During the movement of the puncture mechanism relative to the base, the puncture needle is driven to move relative to the storage cavity of the microfluidic chip to puncture the sealing film on the storage cavity.
[0023] The disengaging mechanism is located on the piercing mechanism and separates the two temperature control modules as the piercing mechanism moves.
[0024] In some embodiments, the piercing mechanism causes the piercing needle to pierce the sealing film on the storage cavity by breaking the connecting rib of the microfluidic chip's piercing needle.
[0025] In some embodiments, after the piercing needle pierces the sealing film, the piercing mechanism further drives the piercing needle to move toward the holding device so that the piercing needle and the cover of the microfluidic chip together seal the storage cavity.
[0026] In some embodiments, the detector includes at least one of the following:
[0027] The rotary valve device includes a rotary valve component and a rotary valve drive mechanism. The rotary valve component is mounted on the piercing mechanism and connects or disconnects from the rotor of the switching valve of the microfluidic chip as the piercing mechanism moves. The rotary valve drive mechanism is driven to connect with the rotary valve component so as to drive the rotor to rotate when the rotary valve component is connected to the rotor, thereby realizing the switching of the valve position of the switching valve.
[0028] The pump assembly includes a connecting nozzle and a drive pump. The connecting nozzle is disposed on a piercing mechanism and connects or disconnects from the communication port of the microfluidic chip as the piercing mechanism moves. The drive pump is connected to the connecting nozzle to drive fluid flow within the microfluidic chip when the connecting nozzle is connected to the communication port.
[0029] In some embodiments, the rotary valve includes a rotary valve shaft, which is used to fit around the valve stem of the rotor and drive the valve stem to rotate under the drive of the rotary valve drive mechanism, so as to realize the switching of the valve position of the switching valve.
[0030] In some embodiments, the inner bore of the rotary valve shaft for engaging with the valve stem is a polygonal bore.
[0031] In some embodiments, along the direction of the rotary valve shaft near the retaining device, the cross-sectional dimensions of one of the inner bore of the rotary valve shaft and the valve stem remain unchanged, while the cross-sectional dimensions of the other change, such that the tightness of the connection between the rotary valve shaft and the valve stem increases along the direction of the rotary valve shaft near the retaining device.
[0032] In some embodiments, the piercing mechanism includes a piercing element that acts on the microfluidic chip during movement relative to the base, causing the piercing needle to move relative to the storage cavity. The piercing element is sleeved outside the rotary valve.
[0033] In some embodiments, the end of the rotary valve member near the retaining device protrudes beyond the end of the piercing member near the retaining device.
[0034] In some embodiments, the distance between the end of the rotary valve near the holding device and the end of the piercing member near the holding device is less than the distance between the top of the rotor and the plane where the connecting rib of the microfluidic chip is located.
[0035] In some embodiments, the pump assembly includes a constraint member and an elastic member, the constraint member supporting the connecting nozzle, and the elastic member being sleeved outside the connecting nozzle and abutting against the constraint member to apply an elastic force toward the connecting nozzle.
[0036] In some embodiments, the drive pump includes a cylinder, a piston rod, and a piston drive mechanism. The piston rod is retractably inserted into the cylinder, and the piston drive mechanism is driven to the piston rod and drives the fluid flow within the microfluidic chip by driving the piston rod to extend and retract.
[0037] In some embodiments, the drive pump includes a guide rod connected to the cylinder and guiding the piston rod during piston rod movement.
[0038] In some embodiments, the detector includes at least one of the following:
[0039] An ultrasonic device includes an ultrasonic transducer and an ultrasonic driving mechanism. The ultrasonic driving mechanism drives the ultrasonic transducer to move relative to the holding device. After the ultrasonic transducer contacts the outer wall of the reaction cavity of the microfluidic chip, it transmits vibration to the reaction cavity of the microfluidic chip.
[0040] A magnetic attraction device includes a magnet and a magnetic attraction driving mechanism. The magnetic attraction driving mechanism drives the magnet to move between a magnetic attraction position and a non-magnetic attraction position to control whether the magnet attracts the magnetic material in the reaction chamber of the microfluidic chip for attracting target objects.
[0041] The detection device is mounted on the base and detects the target analyte amplified in the amplification chamber of the microfluidic chip.
[0042] A monitoring device, mounted on a base, is configured to perform at least one of the following functions: acquiring information about a storage container holding a sample to be added to a storage cavity of a microfluidic chip; acquiring detection item information of the microfluidic chip; monitoring the reaction in the microfluidic chip; and alarming for abnormal conditions. In some embodiments, the ultrasonic device includes a pressure sensor 74 for detecting the pressure applied by the ultrasonic transducer to the reaction cavity. The pressure sensor is located on the side of the ultrasonic transducer away from the holding device and is driven by an ultrasonic drive mechanism to move closer to and further away from the ultrasonic transducer under the drive of the ultrasonic drive mechanism. The ultrasonic drive mechanism drives the ultrasonic transducer to move by moving the pressure sensor after it comes into contact with the ultrasonic transducer.
[0043] In some embodiments, the ultrasonic device includes a blocking element for blocking the ultrasonic transducer as the pressure sensor and the ultrasonic transducer move away from the holding device together, thereby separating the pressure sensor from the ultrasonic transducer.
[0044] In some embodiments, the ultrasonic transducer and / or magnet move in the up-down direction.
[0045] In some embodiments, the monitoring device includes at least one of the following:
[0046] The first barcode scanner is used to scan the barcode on the storage container to obtain samples;
[0047] The second barcode scanner is used to scan the barcode on the microfluidic chip to obtain the detection item information of the microfluidic chip;
[0048] A camera is used to capture the reactions within the microfluidic chip.
[0049] This application also provides a detection system, which includes a microfluidic chip and a detector according to embodiments of this application.
[0050] In this application, because the separating mechanism can separate the two temperature control modules before the temperature-controlled part of the microfluidic chip begins to move outward from between them, the friction between the temperature-controlled part and the two temperature control modules during the removal process can be reduced, thus lowering the risk of damage to the temperature-controlled part due to friction during removal. Therefore, this application can effectively improve the performance of the detector, enabling it to control the microfluidic chip more safely and reliably.
[0051] 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
[0052] 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.
[0053] Figure 1 This is a perspective view of the detection system in the embodiments of this application.
[0054] Figure 2 This is a perspective view of the microfluidic chip in the embodiments of this application.
[0055] Figure 3 This is an exploded view of the microfluidic chip in the embodiments of this application.
[0056] Figure 4 This is a schematic diagram of the combination of the body and rotor of the microfluidic chip in the embodiments of this application.
[0057] Figure 5 This is a perspective view of the detector in the embodiments of this application.
[0058] Figure 6 The structure of the base in an embodiment of this application is shown.
[0059] Figure 7 The structure of the holding device in the embodiments of this application is shown.
[0060] Figure 8 The structure of the retainer in the embodiment of this application is shown.
[0061] Figure 9This diagram illustrates the interaction between the retaining member and the limiting member with the microfluidic chip in an embodiment of this application.
[0062] Figure 10 This is a perspective view of the limiting member in the embodiments of this application.
[0063] Figure 11 This is a first perspective view of the piercing component in an embodiment of this application.
[0064] Figure 12 This is a second perspective view of the piercing component in an embodiment of this application.
[0065] Figure 13 This is a third perspective view of the piercing component in the embodiments of this application.
[0066] Figure 14 The structure of the puncture device in the embodiments of this application is shown.
[0067] Figure 15 This is a schematic diagram of the installation of the rotary valve mechanism on the puncture mechanism in an embodiment of this application.
[0068] Figure 16 The structure of the connecting device in the embodiments of this application is shown.
[0069] Figure 17 This illustration shows a schematic diagram of the connection device being installed on the piercing mechanism in an embodiment of this application.
[0070] Figure 18 This is a perspective view of the drive pump in an embodiment of this application.
[0071] Figure 19 This is an exploded schematic diagram of the drive pump in an embodiment of this application.
[0072] Figure 20 The structure of the temperature control device in the embodiments of this application is shown.
[0073] Figure 21 The structure of the temperature control unit in the embodiment of this application is shown.
[0074] Figure 22 This is a schematic diagram showing the state when the separating mechanism separates the two temperature control modules in an embodiment of this application.
[0075] Figure 23 This is a schematic diagram of the state when the separating mechanism no longer separates the two temperature control modules in the embodiments of this application.
[0076] Figure 24 This is a perspective view of the ultrasonic device in the embodiments of this application.
[0077] Figure 25 This is a schematic diagram illustrating the cooperation between the magnetic suction device, the holding device, and the microfluidic chip in the embodiments of this application.
[0078] Figure 26 This is a schematic diagram of the installation of the monitoring device in an embodiment of this application.
[0079] Explanation of reference numerals in the attached figures:
[0080] 100. Detection system;
[0081] 10. Detector; 101. Puncture assembly;
[0082] 1. Base; 11. Base plate; 12. First side plate; 13. Second side plate; 14. Back plate; 15. Filter; 16. Transformer; 17. Ultrasonic generator; 18. Main unit fan; 19. Switch; 1a. Communication interface;
[0083] 2. Holding device; 21. Holding component; 211. Positioning block; 212. Clearance opening; 22. Support component; 221. Opening; 23. Mounting block; 26. Holding drive mechanism; 261. Holding motor; 262. Holding transmission mechanism; 263. Holding gear; 264. Holding rack; 265. Linear guide slider; 27. Holding detection device; 271. Holding detection component; 272. Holding trigger component; 274. Photoelectric switch; 275. Baffle; 28. Limiting component; 281. Connecting part; 282. Extension part; 283. Snap-fit part; 284. Correction block;
[0084] 3. Piercing device; 31. Piercing bracket; 311. First upright plate; 312. Second upright plate; 313. Horizontal plate; 32. Piercing mechanism; 321. Support plate; 322. Piercing component; 323. Piercing slider; 324. Piercing guide rail; 325. Clearance opening; 326. First groove; 33. Piercing drive mechanism; 331. Piercing motor; 332. Piercing gear; 333. Piercing rack; 34. Piercing detection device; 341. First piercing detection component; 342. Second piercing detection component; 343. Piercing trigger; 345. Opening detection mechanism; 35. Disengaging mechanism; 351. Disengaging component; 352. Rotating bearing; 353. Connecting shaft;
[0085] 4. Rotary valve device; 41. Rotary valve component; 411. Rotary valve shaft; 42. Rotary valve bracket; 43. Rotary valve drive mechanism; 431. Rotary valve motor; 432. Rotary valve transmission mechanism; 433. Belt drive mechanism; 434. Pulley; 436. Belt; 437. Tensioner; 44. Angle detection device; 441. Angle detection component; 442. Hall sensor; 443. Mounting base; 446. Magnet base;
[0086] 5. Pump assembly; 51. Drive pump; 511. Cylinder; 511a. Piston bore; 511b. Connecting hole; 512. Piston rod; 513. Piston drive mechanism; 513a. Lead screw motor; 513b. Motor; 513c. Lead screw; 513d. Nut; 513e. First bearing; 514. Guide rod; 514a. Second bearing; 515. Sealing ring; 516. Stud; 517. Piston detection device; 518 a. Piston detection component; 517b. Piston trigger component; 518. Support device; 518a. Fixing plate; 518b. Baffle; 518c. Sliding plate; 518d. Sealing pressure plate; 519. Connecting pipe; 519a. Pipe joint; 52. Connecting nozzle; 521. Limiting step; 53. Clamp; 532. Second groove; 54. Constraint component; 55. Elastic component; 551. Spring; 56. Guide bearing; 5a. Connecting device;
[0087] 6. Temperature control device; 61. Temperature control module; 611. Heat exchange device; 611a. Semiconductor cooling chip; 611b. Heat transfer plate; 611c. First positioning component; 611d. Second positioning component; 612. Sliding assembly; 612a. Temperature control elastic component; 612b. Support shaft; 612c. Sliding guide mechanism; 613. Heat dissipation device; 613a. Heat sink; 613b. Cooling fan; 613c. Heat sink fixing component; 613d. Connecting block; 62. Opening mechanism; 621. Opening component; 622. Protrusion; 623. Reset elastic component; 624. Shaft; 63. Support plate; 64. Pull plate; 65. Support plate; 66. Temperature control unit;
[0088] 7. Ultrasonic device; 71. Ultrasonic support; 711. Base frame; 712. First side frame; 713. Second side frame; 714. Ultrasonic slide rail; 715. Ultrasonic slider; 72. Ultrasonic transducer; 721. Ultrasonic head; 73. Ultrasonic drive mechanism; 731. Ultrasonic motor; 732. Ultrasonic gear; 733. Ultrasonic rack; 74. Pressure sensor; 75. Ultrasonic detection device; 751. Ultrasonic detection component; 752. Ultrasonic trigger component; 76. Support component; 77. Blocking component; 78. Connecting component;
[0089] 8. Magnetic attraction device; 81. Magnet; 82. Magnetic attraction drive mechanism; 821. Magnetic attraction motor; 83. Magnetic attraction support; 84. Magnetic attraction detection device; 841. First magnetic attraction detection element; 842. Second magnetic attraction detection element; 843. Magnetic attraction trigger element;
[0090] 91. Detection device; 911. Excitation optical fiber; 912. Transmitting optical fiber;
[0091] 92. Monitoring device; 921. First barcode scanner; 922. Second barcode scanner; 923. Camera;
[0092] 20. Microfluidic chip; 201. Body; 201a. Storage chamber; 201b. Mounting slot; 202. Base; 202a. Reaction chamber; 202b. Positioning slot; 202c. Slot; 203. Switching valve; 203a. Rotor; 203b. Valve stem; 203c. Valve seat; 203d. Seat body; 203e. Gasket; 203f. Internal flow channel of valve; 203g. Valve 204. Top cover; 204a. Sample inlet; 204b. Connecting port; 204c. Piercing needle; 204d. Connecting rib; 204e. Stop; 204f. Rib; 204g. Cover body; 204h. Ring-shaped component; 204j. Ventilation channel; 205. Amplification component; 205a. Amplification chamber; 206. Cover plate; 206a. Through hole; 207. Temperature control area. Detailed Implementation
[0093] 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.
[0094] 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.
[0095] 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.
[0096] 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.
[0097] Figures 1-26 The detection system 100 of this application, its microfluidic chip 20, and the detector 10 are illustrated by way of example.
[0098] Reference Figures 1-26 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.
[0099] To make it easier to understand, let's first combine... Figures 2-4The 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 cell-containing sample (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.
[0100] See Figures 2-4 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.
[0101] 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, and 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), and 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.
[0102] 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.
[0103] 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.
[0104] The sealing film is punctured by a puncture needle 204c. In some embodiments, the puncture needle 204c is disposed on the top cover 204.
[0105] 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.
[0106] Specifically, such as Figures 2-4 As shown, in some embodiments, the top cover 204 includes a cover body 204g and an annular member 204h.
[0107] The cover 204 is fitted onto the top of the body 201 and snaps into the body 201 to achieve a fixed connection between the cover 204 and the body 201. The cover 204g is provided with a communication port 204b. The communication port 204b is used to communicate with the drive pump 51 so that the drive pump 51 drives the fluid to flow between different chambers of the microfluidic chip 20 to achieve fluid transfer.
[0108] The outer edge of the annular component 204h is connected to the top wall of the cover 204 via multiple connecting ribs 204d. Simultaneously, the inner edge of the annular component 204h is connected to a stop component 204e via multiple ribs 204f. The stop component 204e is approximately annular and extends from the annular component 204h toward the body 201. The annular component 204h has a sample inlet 204a, which communicates with one of the multiple storage cavities 201a (i.e., the sample chamber) to add the sample to be tested into the corresponding storage cavity 201a.
[0109] 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 204e, 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 film. 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 film.
[0110] The connecting ribs 204d and ribs 204f can be crushed to separate the annular part 204h from the cover 204 and the stop 204e from the annular part 204, so that the piercing needle 204c can pierce the sealing film before extraction begins and cooperate with the cover 6 to reseal the storage cavity 201a after extraction.
[0111] 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.
[0112] 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 204e 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 part 204e 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 part 204e, causing the annular part 204h to separate from the stop part 204e. At this time, the stop part 204e 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.
[0113] 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 204e 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 mechanism 32 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.
[0114] 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.
[0115] In addition, such as Figure 3 As shown, the base 202 is provided with a positioning groove 202b and a slot 202c. The positioning groove 202b is used to engage with the holding device 2 of the detector 10 to realize the installation of the microfluidic chip 20 on the detector 10. The slot 202c is used to engage with the limiting member 28 of the detector 10 mentioned below, so that the limiting member 28 presses the microfluidic chip 20 in place, thereby further fixing the microfluidic chip 20 and preventing the microfluidic chip 20 from moving accidentally during the detection process, which would affect the smoothness, accuracy and consistency of the detection.
[0116] 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.
[0117] 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.
[0118] 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.
[0119] like Figures 2-4As 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.
[0120] 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 seat 203d, a valve stem 203b, and a gasket 203e. The gasket 203e has the same bottom shape as the seat 203d, both being circular. The seat 203d and the gasket 203e are fixedly disposed together. The combined structure of the seat 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.
[0121] 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.
[0122] 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 41 of the rotary valve device 4, thereby facilitating the rotary valve device 4 to reliably drive the valve stem 203b to rotate.
[0123] It is understandable that the structure of the microfluidic chip 20 is not limited to... Figures 2-4 The structure shown, for example, in some other embodiments, may also differ from the microfluidic chip 20 in that it does not... Figures 2-4 Similarly, the main body (excluding the amplification component 205) is cylindrical, but the main body is also flat. For example, the flat microfluidic chip 20 can be found in the applicant's earlier patent application CN111135892A.
[0124] Based on the above introduction to the structure of the microfluidic chip 20, the structure of the detector 10 will be introduced next.
[0125] Figures 5-26 The structure of the detector 10 is shown as an example.
[0126] See Figures 5-26 In some embodiments, the detector 10 includes a base 1, a holding device 2, a temperature control device 6, and a disengaging mechanism 35.
[0127] The base 1 is used to provide an installation foundation for other structural components of the detector 10, thereby supporting the other structural components of the detector 10.
[0128] The holding device 2 is disposed on the base 1 and 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, thereby facilitating the detector 10 to control the microfluidic chip 20.
[0129] The temperature control device 6, mounted on the base 1, is used to control the temperature of the portion 207 of the microfluidic chip 20 to be controlled. It includes two temperature control modules 61. These two modules 61 are opposite to each other and can move relative to each other. The temperature control modules 61 control the portion 207 of the microfluidic chip 20 when it is inserted between them. Typically, the portion 207 includes an amplification chamber 205a. During the operation of the microfluidic chip 20 by the detector 10, the amplification component 205 of the microfluidic chip 20 is inserted between the two temperature control modules 61, bringing the amplification chamber 205a into contact with the two temperature control modules 61. This allows the two temperature control modules 61 to heat or cool the amplification chamber 205a when amplification is needed, providing suitable temperature conditions for the amplification process.
[0130] The separating mechanism 35 is used to separate the two temperature control modules 61 so that the part to be controlled 207 can smoothly move in and out between the two temperature control modules 61.
[0131] In the related technology, the opening mechanism 35 is disposed on the holding device 2 and is immovable relative to the holding device 2. During operation, the opening mechanism 35, driven by the holding device 2, moves close to the temperature control device 6 together with the microfluidic chip 20. It first inserts the part to be temperature controlled 207 of the microfluidic chip 20 between the two temperature control modules 61, opening the two temperature control modules 61. This allows the opening mechanism 35 to open the two temperature control modules 61 before the part to be temperature controlled 207 is inserted between the two temperature control modules 61, reducing the insertion resistance of the part to be temperature controlled 207 and enabling the part to be temperature controlled 207 to be smoothly inserted between the two temperature control modules 61.
[0132] In the aforementioned related technologies, although the disengaging mechanism 35 can open the two temperature control modules 61 before the temperature control part 207 is inserted between them, facilitating the insertion of the temperature control part 207, research has found that since the disengaging mechanism 35 is immovably mounted on the holding device 2, the disengaging mechanism 35, which is inserted between the two temperature control modules 61 before the temperature control part 207, can only separate the two temperature control modules 61 after the temperature control part 207 has started to move outward a certain distance. In other words, at the initial stage of the extraction process of the temperature control part 207, the disengaging mechanism 35 has not yet separated the two temperature control modules 61. Since the two temperature control modules 61 that have not yet separated will rub against the outwardly moving temperature control part 207, it not only increases the difficulty of extraction but also easily damages the temperature control part 207, causing the fluid inside the temperature control part 207 to flow out unexpectedly, causing pollution and affecting the normal use of the detector 10.
[0133] It is evident that while the aforementioned design of the disengaging mechanism 35 facilitates the insertion of the temperature-controlled part 207, it does not facilitate its removal. This can easily cause wear and leakage of the temperature-controlled part 207 during removal, making it difficult for the detector 10 to safely and reliably control the microfluidic chip 20 and affecting the performance of the detector 10.
[0134] Based on the above findings, in order to reduce wear during the extraction of the part to be temperature controlled 207, in the embodiments of this application, the disengaging mechanism 35 is no longer immovably mounted on the holding device 2, but is movably mounted relative to the holding device 2, and separates the two temperature control modules 61 before the part to be temperature controlled 207 begins to move outward from between the two temperature control modules 61, so that the part to be temperature controlled 207 can be moved out from between the two temperature control modules 61.
[0135] Since the separating mechanism 35 no longer separates the two temperature control modules 61 only after the part to be controlled 207 has moved a certain distance outward from between the two temperature control modules 61, but separates the two temperature control modules 61 before the part to be controlled 207 begins to move outward from between the two temperature control modules 61, the two temperature control modules 61 can remain separated throughout the entire removal process of the part to be controlled 207. This effectively reduces the friction between the part to be controlled 207 and the two temperature control modules 61 during the removal process. This not only makes it easier to pull out the part to be controlled 207 smoothly, but also reduces the risk of damage and leakage caused by the friction between the part to be controlled 207 and the two temperature control modules 61 during the removal process. It also facilitates the retraction of the microfluidic chip 20 and enables the detector 10 to control the microfluidic chip 20 more safely and reliably. Therefore, it can effectively improve the performance of the detector 10.
[0136] In order for the separating mechanism 35 to separate the two temperature control modules 61 before the temperature control part 207 begins to move outward from between the two temperature control modules 61, the separating mechanism 35 can be configured in various ways.
[0137] For example, in some embodiments, the disengaging mechanism 35 is still disposed on the holding device 2, but is no longer immovable relative to the holding device 2, but becomes movable relative to the holding device 2. Based on the movably mounted opening mechanism 35 on the holding device 2, when the temperature-controlled part 207 needs to be inserted between the two temperature control modules 61, the opening mechanism 35 acts on the temperature control device 6 before the temperature-controlled part 207, separating the two temperature control modules 61. When the temperature-controlled part 207 needs to be pulled out from between the two temperature control modules 61, the opening mechanism 35 moves relative to the holding device 2 before the holding device 2 begins to move outward, separating the two temperature control modules 61. After that, the holding device 2 begins to move outward relative to the temperature control device 6, causing the temperature-controlled part 207 to move outward. This ensures that the two temperature control modules 61 are already opened in the initial stage of the temperature-controlled part 207 moving outward. In this way, the temperature-controlled part 207 can be smoothly moved out from between the two temperature control modules 61 while the two temperature control modules 61 are kept separate.
[0138] As can be seen, when the disengaging mechanism 35 is movably mounted on the holding device 2, the disengaging mechanism 35 can be controlled to move outward before the holding device 2 during the removal process, so that the disengaging mechanism 35 separates the two temperature control modules 61 before the temperature control part 207 begins to be pulled outward, which facilitates the removal of the temperature control part 207 and reduces the wear of the temperature control part 207 during the removal process.
[0139] For example, in some other embodiments, the disengaging mechanism 35 is no longer located on the holding device 2, but is located on other structural components of the detector 10. Driven by other structural components, it moves relative to the holding device 2, so that whether during insertion or withdrawal, the disengaging mechanism 35 always moves relative to the temperature control device 6 before the temperature control part 207, opening the two temperature control modules 61. This ensures that the two temperature control modules 61 remain open during insertion and withdrawal, facilitating the smooth progress of the insertion and withdrawal process and reducing wear during insertion and withdrawal.
[0140] As an example, see Figure 13 In some embodiments, the detector 10 includes a piercing device 3 for controlling the piercing of the sealing film on the storage cavity 201a of the microfluidic chip 20, and a prying mechanism 35 is disposed on the piercing device 3, and under the action of the piercing device 3, the two temperature control modules 61 are opened before the temperature control part 207 moves outward.
[0141] Specifically, such as Figure 13As shown, the piercing device 3 includes a piercing mechanism 32 and a piercing drive mechanism 33 connected by a drive. The piercing drive mechanism 33 drives the piercing mechanism 32 to move relative to the base 1. During the movement of the piercing mechanism 32 relative to the base 1, it drives the piercing needle 204c to move relative to the storage cavity 201a of the microfluidic chip 20, piercing the sealing film on the storage cavity 201a. The separating mechanism 35 is disposed on the piercing mechanism 32 and separates the two temperature control modules 61 during the movement of the piercing mechanism 32.
[0142] Since the piercing mechanism 32 will act before the holding device 2 after the test, to release the constraint of the piercing mechanism 32 on the microfluidic chip 20 on the holding device 2, and thus facilitate the microfluidic chip 20 to leave the detector 10 (i.e., exit the chamber) under the action of the holding device 2, the separating mechanism 35 is set on the piercing mechanism 32. It can take advantage of the characteristic that the piercing mechanism 32 moves before the microfluidic chip 20 exits the chamber to separate the two temperature control modules 61. This allows the separating mechanism 35 to separate the two temperature control modules 61 before the part to be temperature controlled 207 starts to move outward from between the two temperature control modules 61, making it easier to pull out the part to be temperature controlled 207 and reducing the wear of the part to be temperature controlled 207 during the extraction process.
[0143] It can be seen that by setting the opening mechanism 35 on the piercing mechanism 32 of the piercing device 3, the two temperature control modules 61 can be pre-opened before the temperature control part 207 is removed, which effectively reduces the risk of wear and leakage of the temperature control part 207 during the extraction process and improves the safety of the detector 10.
[0144] Furthermore, by placing the disengaging mechanism 35 on the piercing mechanism 32 of the piercing device 3, it is easier for the disengaging mechanism 35 to open the two temperature control modules 61 before the temperature control part 207 is inserted, thus reducing wear on the temperature control part 207 during insertion. Specifically, by controlling the piercing mechanism 32 to move the disengaging mechanism 35 to the open position (i.e., the position where the disengaging mechanism 35 separates the two temperature control modules 61) before the temperature control part 207 is inserted, the two temperature control modules 61 can be pre-opened before insertion into the temperature control part 207.
[0145] It is evident that by setting the opening mechanism 35 on the piercing mechanism 32, it is convenient to both pull out the part to be controlled 207 and insert the part to be controlled 207, which can more reliably reduce the wear of the part to be controlled 207 and improve the safety of the detector 10.
[0146] Furthermore, by mounting the disengaging mechanism 35 on the piercing mechanism 32 and moving together with it under the drive of the piercing drive mechanism 33, it is unnecessary to have a separate drive mechanism for the disengaging mechanism 35 to move relative to the holding device 2. This simplifies the structure and makes control more convenient. Simultaneously, since the disengaging mechanism 35 completes the disengaging action during the movement of the piercing mechanism 32 without requiring additional time, it also helps to shorten the control time of the detector 10 on the microfluidic chip 20, thus improving the working efficiency of the detector 10.
[0147] It is evident that by placing the prying mechanism 35 on the piercing mechanism 32 and coupling the prying function with the piercing function, the two temperature control modules 61 can be pre-opened before the temperature-controlled part 207 is activated, based on a simpler structure and a simpler control process, effectively reducing the risk of wear and leakage of the temperature-controlled part 207.
[0148] In the case where the puncture needle 204c is disposed in the microfluidic chip 20 and is connected and fixed by the connecting rib 204d, the puncture mechanism 32 can puncture the sealing film on the storage cavity 201a by breaking the connecting rib 204d of the microfluidic chip 20 connecting the puncture needle 204c.
[0149] Furthermore, in microfluidic chips such as 20 Figures 2-4 As shown, when the cover plate 206 is also included, after the piercing needle 204c pierces the sealing film, the piercing mechanism 32 can further drive the piercing needle 204c to move toward 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 realizing the resealing of the storage cavity 201a to prevent the leakage of waste liquid in the storage cavity 201a.
[0150] To facilitate opening the two temperature control modules 61 by disengaging mechanism 35, see [link / reference] Figure 13 as well as Figures 20-23 In some embodiments, the separating mechanism 35 includes a separating element 351, which is rotatably disposed, and the separating mechanism 35 separates the two temperature control modules 61 through the separating element 351.
[0151] Since the disengaging component 351 can rotate, it experiences less friction when acting on the temperature control device 6. This helps reduce the friction between the disengaging mechanism 35 and the temperature control device 6 during their movement, allowing the disengaging mechanism 35 to reach the open position more smoothly and separate the two temperature control modules 61. Furthermore, the lower friction also helps reduce wear during the interaction between the disengaging component 351 and the temperature control device 6, extending their service life.
[0152] As an example of the rotatable push-opening member 351, see Figure 13 The push-opening component 351 includes a rotating bearing 352. Because the rotating bearing 352 can rotate smoothly, there is less friction and better performance.
[0153] In the foregoing embodiments, the movement of the disengaging mechanism 35 relative to the holding device 2 can be a vertical movement. In this case, the disengaging mechanism 35 is configured to move vertically relative to the holding device 2, and during the vertical movement, the disengaging mechanism 35 separates the two temperature control modules 61. The vertically moving disengaging mechanism 35 can easily separate the two temperature control modules 61, and it is particularly suitable for coupling with the piercing device 3, so that the piercing device 32 drives the disengaging mechanism 35 to move vertically together during the vertical movement, separating the two temperature control modules 61. At the same time, the vertically moving disengaging mechanism 35 is also particularly convenient to cooperate with the horizontally moving holding device 2 to achieve the pre-opening of the two temperature control modules 61.
[0154] Additionally, see Figure 12 In some embodiments, the detector 10 includes an opening detection mechanism 345 that detects whether the disengaging mechanism 35 has reached the open position. When the disengaging mechanism 35 reaches the open position, it separates the two temperature control modules 61.
[0155] Based on the set opening detection mechanism 345, it is possible to determine more timely and accurately whether the disengaging mechanism 35 has reached the opening position, and thus more timely and accurately determine whether the two temperature control modules 61 have been separated. This facilitates the control of the holding device 2. For example, after the detection is completed, the holding device 2 can be controlled to move the microfluidic chip 20 outward from between the two temperature control modules 61 after the opening detection mechanism 345 detects that the disengaging mechanism 35 has reached the opening position, so as to reduce the wear of the temperature-controlled part 207 during the extraction process.
[0156] Meanwhile, when the dispersing mechanism 35 is mounted on the piercing mechanism 32, the detection signal from the opening detection mechanism 345 can also serve as a basis for controlling the action of the piercing mechanism 32. For example, when the opening detection mechanism 345 detects that the dispersing mechanism 35 has reached the open position, the distance from the open position to the position where the connecting rib 204d is crushed can be calculated. Based on the calculated distance, the required number of steps for the piercing motor 331 in the piercing drive mechanism 33 can be determined. This allows the piercing mechanism 32 to accurately reach the crushing position and crush the connecting rib 204d by controlling the piercing motor 331 to rotate the corresponding number of steps. This not only allows for convenient and accurate control of the piercing function, but also simplifies the structure and reduces costs because there is no need to set up a separate detection component to detect whether the piercing mechanism 32 has reached the crushing position.
[0157] See Figures 20-23 In order to facilitate cooperation with the opening mechanism 35 to open the two temperature control modules 61, in some embodiments, the temperature control device 6 includes two opening parts 621, which are connected to the two temperature control modules 61 in a one-to-one correspondence, and the opening mechanism 35 separates the two temperature control modules 61 by pushing the two opening parts 621 away from each other.
[0158] Since the disengaging mechanism 35 controls the separation of the two temperature control modules 61 by pushing the two opening parts 621 away from each other, in this case, the disengaging mechanism 35 does not need to act directly on the two temperature control modules 61. For example, the disengaging mechanism 35 does not need to be directly inserted between the two temperature control modules 61 which have almost no gap (close or only a small gap). Therefore, it can effectively reduce the difficulty of separating the two temperature control modules 61 and is less likely to cause wear on the temperature control elements (such as the heat transfer plate 611b mentioned later) in the temperature control modules 61. This is conducive to achieving the opening function more safely and smoothly.
[0159] To facilitate the cooperation between the opening component 621 and the disengaging mechanism 35 to achieve the opening function, see [reference needed]. Figures 20-23 In some embodiments, the opening member 621 includes a protrusion 622, and the disengaging mechanism 35 pushes the two opening mechanisms 62 away from each other by acting on the protrusion 622.
[0160] The protrusion 622 makes it easier for the opening part 621 to contact the opening mechanism 35, so that the opening function can be realized smoothly.
[0161] Among them, such as Figures 21-23As shown, in some embodiments, the surface of the protrusion 622 that contacts the disengaging mechanism 35 is arc-shaped. This arc-shaped surface of the opening member 621 that contacts the disengaging mechanism 35 helps to reduce the friction between the opening member 621 and the disengaging mechanism 35, making it easier to achieve the opening function. In particular, when the disengaging member 351 of the disengaging mechanism 35 is a rotating body, the arc-shaped surface of the opening member 621 can better cooperate with the disengaging member 351 to achieve the opening function.
[0162] Additionally, see also Figures 20-23 In some embodiments, the temperature control device 6 includes a reset elastic member 623, which abuts against the opening member 621 and applies an elastic force to the opening member 621 to bring the two opening members 621 closer to each other.
[0163] Based on the reset elastic element 623, when the disengaging mechanism 35 enters between the two opening elements 621 and applies a pushing force to the two opening elements 621, the reset elastic element 623 can retract so that the two opening elements 621 move away from each other, thereby smoothly driving the two temperature control modules 61 to separate from each other. When the disengaging mechanism 35 no longer applies a pushing force to the two opening elements 621, the reset elastic element 623 can release the stored elastic force, so that the opening elements 621 reset, driving the two temperature control modules 61 to reset.
[0164] As can be seen, the reset elastic element 623 can facilitate the automatic reset of the two opening elements 621 and the two temperature control modules 61 without affecting the opening function. After the two temperature control modules 61 are reset, they can make close contact with the temperature control part 207 inserted between them to achieve a better temperature control effect, or they can wait for the temperature control part 207 of the next microfluidic chip 20 to be inserted.
[0165] In the foregoing embodiments, in order for the temperature-controlled portion 207 of the microfluidic chip 20 fixed on the holding device 2 to be inserted and removed between the two temperature control modules 61, the holding device 2 and the temperature control device 6 are relatively movable. For example, the temperature control device 6 can move while the holding device 2 remains stationary, or the holding device 2 can move while the temperature control device 6 remains stationary, or both the temperature control device 6 and the holding device 2 can move. For example, as shown... Figure 7As shown, in some embodiments, the holding device 2 is horizontally movable relative to the base 1, and the detector 10 includes a holding drive mechanism 26, which is drivenly connected to the holding device 2 to drive the holding device 2 to move horizontally closer to or away from the temperature control device 6. In this case, the temperature control device 6 does not need to actively move closer to or away from the holding device 2; the holding device 2 only needs to move horizontally to drive the microfluidic chip 20 closer to or away from the temperature control device 6, thereby realizing the insertion and extraction of the part 207 to be temperature controlled. The fact that the holding device 2 moves horizontally, rather than vertically, helps to reduce the size of the detector 10 and facilitates cooperation with the vertically moving prying mechanism 35 and piercing mechanism 32 to achieve the required functions.
[0166] As an example of the holding device 2 in the foregoing embodiments, see Figures 7-8 The holding device 2 includes a holding member 21, on which a positioning block 211 is provided. The positioning block 211 is used to engage with the positioning groove 202b of the microfluidic chip 20 to fix the microfluidic chip 20. This holding device 2 is suitable for microfluidic chips 20 with positioning grooves 202b, and is particularly suitable for... Figures 2-4 The microfluidic chip 20 with a positioning groove 202b on the base 202 of the microfluidic chip 20 can be easily installed and fixed.
[0167] In addition, to improve the installation stability of the microfluidic chip 20, the microfluidic chip 20 is as follows: Figures 2-4 In the case of card slot 202c shown, see Figures 9-10 In some embodiments, the detector 10 includes a limiting member 28, which is inserted into the slot 202c of the microfluidic chip 20 to press the microfluidic chip 20.
[0168] Since the limiting member 28 can further press the microfluidic chip 20 onto the holding device 2 while the holding device 2 is fixing the microfluidic chip 20, the installation stability of the microfluidic chip 20 can be further improved, and the accidental movement of the microfluidic chip 20 during operation can be more reliably prevented, so as to avoid affecting the smooth implementation of the operation process, as well as the detection accuracy and consistency due to the accidental movement of the microfluidic chip 20.
[0169] To facilitate the insertion of the limiting member 28 into the slot 202c of the microfluidic chip 20, see [reference needed]. Figure 20In some embodiments, the limiting member 28 is disposed on the temperature control device 6 so that it can be inserted into the slot 202c of the microfluidic chip 20 during the insertion of two temperature control modules 61 into the part to be temperature controlled 207. This arrangement utilizes the inherent relative motion between the temperature control device 6 and the holding device 2 to achieve the insertion of the limiting member 28 into the slot 202c, which is simple and convenient. The limiting member 28 can be inserted into the slot 202c as the temperature control device 6 and the holding device 2 approach each other, without the need for separate driving of the limiting member 28 or a separate driving mechanism. Therefore, the structure is simple, easy to control, small in size, and highly efficient.
[0170] Back Figures 9-10 In some embodiments, the limiting member 28 is provided with a correction block 284, and the width of the correction block 284 gradually decreases along the direction in which the limiting member 28 is inserted into the slot 202c. Thus, during the insertion of the limiting member 28 into the slot 202c, the correction block 284 can guide the limiting member 28, correcting its deviation and preventing it from failing to insert smoothly due to misalignment. Furthermore, the correction block 284 also enhances the clamping effect of the limiting member 28 on the microfluidic chip 20, achieving a more stable installation of the microfluidic chip 20.
[0171] Specifically, by Figure 10 It is understood that in some embodiments, the limiting member 28 is provided with two correction blocks 284, which are located on opposite sides of the limiting member 28 to reliably correct deviation.
[0172] See Figures 5-26 As an improvement to the foregoing embodiments, the detector 10 further includes at least one of the following: a rotary valve device 4, a pump assembly 5, an ultrasonic device 7, a magnetic suction device 8, a detection device 91, and a monitoring device 92.
[0173] Next, we will introduce the rotary valve device 4, pump assembly 5, ultrasonic device 7, magnetic suction device 8, detection device 91, and monitoring device 92 in sequence.
[0174] First, let's introduce the rotary valve device 4.
[0175] The rotary valve device 4 is used to rotate the switching valve 203 of the microfluidic chip 20 to control the fluid in the microfluidic chip 20 to flow sequentially, thereby controlling the extraction and amplification processes to proceed in an orderly manner.
[0176] As an example, see Figures 11-15 The rotary valve device 4 includes a rotary valve component 41 and a rotary valve drive mechanism 43. The rotary valve component 41 is detachably connected to the rotor 203a of the switching valve 203. The rotary valve drive mechanism 43 is drivenly connected to the rotary valve component 41 so that when the rotary valve component 41 is connected to the rotor 203a, it drives the rotor 203a to rotate, thereby realizing the switching of the valve position of the switching valve 203.
[0177] By setting a rotary valve device 4 in the detector 10, the detector 10 can have a rotary valve function, which effectively enriches the functions of the detector 10.
[0178] Among them, the microfluidic chip 20 for rotor 203a includes valve stem 203b (see Figures 2-4 ),like Figures 11-15 As shown, the rotary valve component 41 may include a rotary valve shaft 411, which is used to be sleeved on the valve stem 203b of the rotor 203a and drives the valve stem 203b to rotate under the drive of the rotary valve drive mechanism 43, so as to realize the switching of the valve position of the switching valve 203.
[0179] And, see also Figures 11-15 In valve stem 203b, such as Figures 2-4 In the case of the polygonal outer surface shown, the inner hole of the rotary valve shaft 411 for cooperating with the valve stem 203b can be a polygonal hole. This can effectively prevent relative rotation between the rotary valve shaft 411 and the valve stem 203b, and facilitate the rotary valve shaft 411 to drive the valve stem 203b to rotate for valve position switching.
[0180] See Figures 11-15 In some embodiments where the detector 10 includes a piercing device 3, a rotary valve 41 is disposed on the piercing mechanism 32 and connects or separates from the rotor 203a as the piercing mechanism 32 moves. This integration of the rotary valve 41 onto the piercing device 3 not only makes the detector 10 more compact, but also allows the rotary valve 41 to move together with the piercing mechanism 32 under the drive of the piercing drive mechanism 33. This eliminates the need for a separate drive mechanism for the rotary valve 41 to move it closer to or away from the holding device 2, connecting or separating it from the rotor 203a of the microfluidic chip 20 on the holding device 2. Therefore, the structure is simpler and control is more convenient. Furthermore, since the rotary valve 41 can connect or separate from the rotor 203a during the movement of the piercing mechanism 32 without additional time commitment, it also helps to shorten the control time of the detector 10 on the microfluidic chip 20, improving the working efficiency of the detector 10.
[0181] It is evident that by placing the rotary valve 41 on the puncture mechanism 32, the structure and control process of the detector 10 can be effectively simplified, and the working efficiency of the detector 10 can be improved.
[0182] Among them, see Figure 11 and Figure 12 In some embodiments, the piercing mechanism 32 includes a piercing element 322, which acts on the microfluidic chip 20 during the movement of the piercing element 322 relative to the base 1, causing the piercing needle 204c to move relative to the storage cavity 201a. The piercing element 322 is sleeved on the outside of the rotary valve 41.
[0183] Since the piercing element 322 is fitted outside the rotating valve 41, the rotating valve 41 does not need to occupy excessive additional space, thus allowing for a more compact overall structure of the detector 10. Furthermore, with the piercing element 322 fitted outside the rotating valve 41, the rotating valve 41 and the piercing element 322 will not interfere with each other, and in particular, it can adapt to… Figures 2-4 As shown, the valve stem 203b is surrounded by the annular part 204h and the connecting rib 204d, which facilitates the piercing part 322 and the rotary valve part 41 to act on the annular part 204h and the valve stem 203b respectively.
[0184] And, see also Figure 11 and Figure 12 In some embodiments, the end of the rotary valve 41 near the retaining device 2 protrudes beyond the end of the piercing member 322 sleeved on the outside of the rotary valve 41 near the retaining device 2. This relative positional relationship is related to... Figures 2-4 The characteristic that the top of the valve stem 203b is lower than the upper surface of the annular part 204h makes it easier for the piercing part 322 and the rotary valve part 41 to act on the annular part 204h and the valve stem 203b, respectively.
[0185] When one end of the rotary valve 41 near the holding device 2 protrudes beyond the end of the piercing member 322 near the holding device 2 that is sleeved outside the rotary valve 41, the distance between the end of the rotary valve 41 near the holding device 2 and the end of the piercing member 322 near the holding device 2 can be less than the plane where the top of the rotor 203a and the connecting rib 204d are located (i.e., Figure 2-4 The distance between the upper surface of the annular component 204h and the rotor 203a is such that the rotary valve component 41 only begins to connect with the rotor 203a after the piercing component 322 has broken the connecting rib 204d. This helps to prevent the force between the rotary valve device 4 and the rotor 203a from affecting the smooth realization of the piercing function, and also makes the connection between the rotary valve device 4 and the rotor 203a occur before the second-stage pressing of the microfluidic chip 20 by the piercing mechanism 32 and after the sealing film is pierced, which makes it easier for the piercing step, the rotary valve step and the second-stage pressing step to be performed sequentially.
[0186] Next, we will introduce pump assembly 5.
[0187] Pump assembly 5 is used to drive the flow of fluid in microfluidic chip 20 to control the sequential execution of each step.
[0188] See Figure 5 , Figures 11-12 as well as Figures 16-19In some embodiments, the pump assembly 5 includes a connector 52 and a drive pump 51. The connector 52 is detachably connected to a port 204b of the microfluidic chip 20. The drive pump 51 communicates with the connector 52 to drive fluid flow within the microfluidic chip 20 when the connector 52 is connected to the port 204b.
[0189] By incorporating a pump assembly 5 into the detector 10, the detector 10 can be equipped with a fluid drive function, effectively enriching the functionality of the detector 10.
[0190] See Figures 16-19 In some embodiments where the detector 10 includes a piercing device 3, the connecting nozzle 52 is disposed on the piercing mechanism 32 and connects or disconnects from the connecting port 204b of the microfluidic chip 20 as the piercing mechanism 32 moves.
[0191] Since the connecting nozzle 52 is integrated into the piercing mechanism 32, the structure of the detector 10 is more compact. Furthermore, since the connecting nozzle 52 can move together with the piercing mechanism 32 under the drive of the piercing drive mechanism 33, there is no need to drive the connecting nozzle 52 to move separately, nor is there a need to equip the connecting nozzle 52 with a separate drive mechanism. Therefore, the structure is simple, the control is convenient, the size is small, and the efficiency is high.
[0192] Additionally, see Figures 11-12 as well as Figures 16-17 In some embodiments, the pump assembly 5 includes a constraint member 54 and an elastic member 55. The constraint member 54 supports the connecting nozzle 52, and the elastic member 55 is sleeved on the outside of the connecting nozzle 52 and abuts against the constraint member 54, applying an elastic force to the connecting nozzle 52 toward the connecting port 204b. Based on this, the connecting nozzle 52 has a certain amount of room to move, which helps prevent damage to the connecting nozzle 52 during connection with the connecting port 204b due to misoperation or abnormality of the drive mechanism.
[0193] Figures 18-19 The structure of the drive pump 51 is shown as an example.
[0194] See Figure 18 and Figure 19 In some embodiments, the drive pump 51 includes a cylinder 511, a piston rod 512, and a piston drive mechanism 513. The piston rod 512 is retractably inserted into the cylinder 511, and the piston drive mechanism 513 is drivenly connected to the piston rod 512. By driving the piston rod 512 to extend and retract, the fluid flow within the microfluidic chip 20 is driven. In this case, the drive pump 51 is an injection pump, which can drive the fluid flow within the microfluidic chip 20 by evacuating or venting the microfluidic chip 20.
[0195] And, see also Figure 18 and Figure 19In some embodiments, the drive pump 51 includes a guide rod 514 connected to the cylinder 511, which guides the piston rod 512 during its movement. Due to the guiding effect of the guide rod 514, the piston rod 512 is less prone to deflection during movement, thus improving the operational reliability of the drive pump 51 and enabling it to more accurately control the fluid within the microfluidic chip 20 to flow in the desired sequence.
[0196] Next, we will introduce the ultrasonic device 7 and the magnetic attraction device 8.
[0197] Both the ultrasonic device 7 and the magnetic attraction device 8 are used to assist in the extraction of the target analyte. The ultrasonic device 7 assists in the extraction by generating ultrasonic excitation. The magnetic attraction device 8 assists in the extraction by adsorbing the magnetic material used in the extraction process.
[0198] 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.
[0199] 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. 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 convenient and efficient lysis to obtain more nucleic acids, thereby improving the success rate of nucleic acid detection.
[0200] 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. This involves washing with a washing solution to separate the target analyte from other inhibitors, ultimately obtaining a high-purity target analyte. The washing process may need to be repeated several times, all within reaction chamber 202a. After each washing, the waste liquid can be discharged, leaving only the purified target analyte in reaction chamber 202a.
[0201] 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.
[0202] 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.
[0203] Figure 24 The structure of the ultrasonic device 7 is shown as an example.
[0204] See Figure 24 In some embodiments, the ultrasonic device 7 includes an ultrasonic transducer 72 and an ultrasonic driving mechanism 73. The ultrasonic driving mechanism 73 drives the ultrasonic transducer 72 to move relative to the holding device 2. After the ultrasonic transducer 72 contacts the outer wall of the reaction chamber 202a of the microfluidic chip 20, it transmits vibration to the reaction chamber 202a of the microfluidic chip 20.
[0205] During cell lysis, the ultrasonic transducer 72 contacts the outer wall of the reaction chamber 202a and can apply vibration to the reaction chamber 202a to cause the cells in the reaction chamber 202a to lyse and release nucleic acids.
[0206] During the nucleic acid washing process, the ultrasonic transducer 72 transmits ultrasonic vibrations to the reaction chamber 202a, which also mixes the reagents and magnetic beads, so that the magnetic beads can better adsorb nucleic acids and wash away impurities more thoroughly.
[0207] It is evident that the ultrasonic device 7 can achieve ultrasonic lysis and mixing functions, which is beneficial to the smooth progress of the extraction process.
[0208] See also Figure 24 In some embodiments, the ultrasonic device 7 includes a pressure sensor 74, which detects the pressure exerted by the ultrasonic transducer 72 on the reaction chamber 202a. The pressure sensor 74 is located on the side of the ultrasonic transducer 72 away from the holding device 2 and is driven by an ultrasonic driving mechanism 73. Driven by the ultrasonic driving mechanism 73, the pressure sensor 74 moves closer to and further away from the ultrasonic transducer 72. The ultrasonic driving mechanism 73 drives the ultrasonic transducer 72 to move by moving the pressure sensor 74 after it comes into contact with the transducer. In this case, the ultrasonic driving mechanism 73 does not directly drive the ultrasonic transducer 72, but rather drives it by moving the pressure sensor 74 after it comes into contact with the transducer. Because the relative movement between the pressure sensor 74 and the ultrasonic transducer 72, and the relative movement between the ultrasonic transducer 72 and the holding device 2, are completed under the same driving mechanism, no additional driving mechanism is needed. Therefore, the structure is simpler, which helps save costs and reduce size.
[0209] In the case where the ultrasonic drive mechanism 73 drives the ultrasonic transducer 72 via the pressure sensor 74, see [link to relevant documentation]. Figure 24 In some embodiments, the ultrasonic device 7 includes a blocking member 77 for blocking the ultrasonic transducer 72 as the pressure sensor 74 and the ultrasonic transducer 72 move away from the holding device 2 together, thereby separating the pressure sensor 74 from the ultrasonic transducer 72.
[0210] Based on the above settings, after the ultrasonic transducer 72 moves away from the holding device 2 by the pressure sensor 74, the blocking member 77 can be used to prevent the ultrasonic transducer 72 from continuing to move away from the holding device 2 along with the pressure sensor 74, so that the ultrasonic transducer 72 stops at the preset distance, while the pressure sensor 74 can continue to move away from the holding device 2 under the drive of the ultrasonic driving mechanism 73, thereby separating the pressure sensor 74 from the holding device 2. In this way, the pressure sensor 74 can be prevented from being continuously pressured, which is beneficial to extending the service life of the pressure sensor 74.
[0211] Additionally, see Figure 24 In some embodiments, the ultrasonic transducer 72 moves along the vertical direction, which facilitates the coordination of the ultrasonic device 7 with other mechanisms such as the holding device 2, and makes the overall layout more reasonable, which helps to reduce the footprint of the detector 10.
[0212] Figure 25 The structure of the magnetic attraction device 8 is shown as an example.
[0213] See Figure 25 In some embodiments, the magnetic attraction device 8 includes a magnet 81 and a magnetic attraction driving mechanism 82. The magnetic attraction driving mechanism 82 drives the magnet 81 to move between a magnetic attraction position and a non-magnetic attraction position to control whether the magnet 81 adsorbs the magnetic material in the reaction chamber 202a of the microfluidic chip 20 for adsorbing the target, thereby meeting the different needs of the sample lysis and target washing process and the target elution and target transfer process from the reaction chamber 202a to the amplification chamber 205a, so that the target extraction process can be carried out more smoothly.
[0214] And, see also Figure 25 In some embodiments, the magnet 81 moves in the up-down direction, which facilitates the cooperation between the magnetic attraction device 8 and other mechanisms such as the holding device 2, and makes the overall layout more reasonable, which helps to reduce the footprint of the detector 10.
[0215] Next, we will introduce the detection device 91.
[0216] See Figure 1 and Figure 5 The detection device 91 is mounted on the base 1 and detects the target material amplified in the amplification chamber 205a of the microfluidic chip 20.
[0217] By setting a detection device 91 in the detector 10, the detector 10 can be integrated with the target object detection function, which effectively enriches the function of the detector 10.
[0218] In some embodiments, the detection device 91 is a fluorescence detection device, which emits excitation light into the amplification chamber 205a to excite fluorescence, and recovers and detects the excited fluorescence. The presence and quantity of the target object are determined based on the different intensities of the fluorescence generated in the amplification chamber 205a.
[0219] Furthermore, in some embodiments, the detection device 91 is a multi-channel fluorescence detection device, which switches different optical paths by moving or rotating its internal mechanism, thereby realizing the identification and detection of different target objects in the same reaction.
[0220] Since the detection device 91 can adopt an existing structure, and the improvement of this application does not lie in the specific structure of the detection device 91, this application will not provide further details.
[0221] Next, we will introduce the monitoring device 92.
[0222] See Figure 5 and Figure 26The monitoring device 92 is mounted on the base 1 and is used to perform at least one of the following functions: acquiring information about the storage container containing the sample to be added to the storage cavity 201a of the microfluidic chip 20, acquiring detection item information of the microfluidic chip 20, monitoring the reaction in the microfluidic chip 20, and alarming for abnormal situations.
[0223] Specifically, such as Figure 26 As shown, in some embodiments, the monitoring device 92 includes at least one of the following:
[0224] The first barcode scanner 921 is used to scan the barcode on the storage container to obtain sample information;
[0225] The second barcode scanner 922 is used to scan the barcode on the microfluidic chip 20 to obtain the detection item information of the microfluidic chip 20;
[0226] Camera 923 is used to capture the reaction in microfluidic chip 20.
[0227] By scanning the barcode on the storage container, the information of the sample to be added can be easily identified, so that the subsequent testing steps can be performed correctly. It also makes it easy to determine whether the sample to be added is correct, so as to avoid sample misfilling and test failure.
[0228] By scanning the barcode on the microfluidic chip 20, it is easy to determine whether the microfluidic chip 20 used is the one required for the test, so as to avoid the situation where the test report is incorrect due to the operator picking up the wrong microfluidic chip 20.
[0229] By monitoring the reaction in the microfluidic chip 20, such as whether the reagent or waste liquid is completely drawn into or discharged from the reaction chamber 202a in real time, and the mixing of the reagent magnetic beads in the reaction chamber 202a in real time, it is convenient to determine the progress of the reaction and to respond based on the monitored information.
[0230] By issuing alarms for abnormal situations, operators can promptly detect and handle these situations, enabling timely recovery of the testing process.
[0231] As can be seen, based on the monitoring device 92, the progress of the inspection can be easily understood, enabling the entire inspection process to proceed accurately and smoothly.
[0232] The following will be about Figures 5-26 The detector 10 shown will be further described.
[0233] First, it should be noted that the directional terms used below, such as "front, back, up, down, left, right," "horizontal, vertical, perpendicular, horizontal," and "top, bottom," all indicate directions or positional relationships based on... Figure 1 and Figure 5 The orientation or positional relationship shown, wherein: the relative arrangement direction of the holding device 2 and the temperature control device 6 is taken as the front-back direction, in Figure 1 and Figure 5 The coordinate axis X is used to represent this, which can also be called the first direction X. Here, the orientation of the holding device 2 relative to the temperature control device 6 is considered "front," and the orientation of the temperature control device 6 relative to the holding device 2 is considered "rear." Simultaneously, the relative arrangement direction of the base 1 and the holding device 2 is taken as the vertical direction. Figure 1 The coordinate axis Z is used to represent the direction, which can also be called the second direction Z. Here, the orientation of the base 1 relative to the holding device 2 is "down," and the orientation of the holding device 2 relative to the base 1 is "up." Furthermore, the direction perpendicular to the first direction X and the second direction Z is defined as the left-right direction. Figure 1 The coordinate system uses the Y-axis, also known as the third-order Y-axis, where left and right are defined as when facing forward. This defined orientation is consistent with the orientation of the detector 10 when it is normally placed.
[0234] The detector 10 in this embodiment is used for... Figures 2-4 The microfluidic chip 20 shown is manipulated to realize automatic control of each step of nucleic acid detection based on the microfluidic chip 20, so as to improve the efficiency of microfluidic detection and improve the application prospects of microfluidic technology.
[0235] like Figures 5-26 As shown, in this embodiment, the detector 10 includes a base 1, a holding device 2, a piercing device 3, a prying mechanism 35, a rotary valve device 4, a pump assembly 5, a temperature control device 6, an ultrasonic device 7, a magnetic suction device 8, a detection device 91, and a monitoring device 92.
[0236] The holding device 2, piercing device 3, opening mechanism 35, rotary valve device 4, pump assembly 5, temperature control device 6, ultrasonic device 7, magnetic suction device 8, detection device 91 and monitoring device 92 are all mounted on the base 1. Furthermore, the connecting device 5a of the opening mechanism 35, rotary valve device 4 and pump assembly 5 are all integrated on the piercing device 3 to form the piercing assembly 101.
[0237] The following sections will introduce each module separately.
[0238] First, let's introduce base 1.
[0239] The base 1 is used to provide an installation foundation for other modules such as the holding device 2, so as to realize the installation and fixation of other modules.
[0240] Figure 6 The structure of base 1 in this embodiment is shown.
[0241] like Figure 6As shown, in this embodiment, the base 1 includes a base plate 11, a first side plate 12, a second side plate 13, and a back plate 14. The first side plate 12 and the second side plate 13 are respectively connected to the left and right ends of the base plate 11 and are opposite to each other. The back plate 14 is connected to the rear end of the base plate 11 and is connected to both the first side plate 12 and the second side plate 13.
[0242] Figure 6 Some auxiliary components mounted on base 1 are also shown.
[0243] like Figure 6 As shown, in this embodiment, a transformer 16 and an ultrasonic generator 17 are mounted on the base plate 11. Both the transformer 16 and the ultrasonic generator 17 are fixed to the upper surface of the base plate 11, arranged sequentially along the direction from the first side plate 12 to the second side plate 13 (i.e., from left to right), and spaced apart from each other. The transformer 16 converts 220V AC power into 24V DC power for use by the various electrical components of the detector 10 (e.g., the motors mentioned later). The ultrasonic generator 17 converts the 24V DC power into a high-frequency AC signal that matches the ultrasonic transducer 72 of the ultrasonic device 7, thereby driving the ultrasonic transducer 72 to operate.
[0244] At the same time, such as Figure 6 As shown, in this embodiment, both the first side plate 12 and the second side plate 13 are provided with communication interfaces 1a, and the second side plate 13 is provided with a switch 19. The communication interface 1a is soldered to a circuit board (not shown) fixed on the side plate (first side plate 12 or second side plate 13), and is used to enable signal communication between the detector 10 and the outside world. Specifically, the communication interface 1a on the first side plate 12 is used to connect to other devices for communication, and the communication interface 1a on the second side plate 13 is used for copying nucleic acid detection data and upgrading the program. In this embodiment, the communication interface 1a is configured as a USB interface, and the communication interface 1a on the first side plate 12 is closer to the back plate 14 than the communication interface 1a on the second side plate 13. The switch 19 is fixed to the second side plate 13 and is used to turn the detector 10 on and off.
[0245] In addition, such as Figure 6 As shown, in this embodiment, the backplate 14 is equipped with a filter 15 and a mains fan 18. The filter 15 is connected to AC power and electrically connected to all electrical components of the detector 10 to prevent interference from the power line from entering the detector 10. The mains fan 18 is used for heat dissipation of the entire unit.
[0246] Next, we will introduce the holding device 2.
[0247] The holding device 2 is used to hold and transport the microfluidic chip 20 to a target position that cooperates with other modules, so that the piercing device 3 and the rotary valve device 4 can manipulate the microfluidic chip 20. Furthermore, the holding device 2 is also used to remove the microfluidic chip 20 from the target position after the detection is completed, so that the microfluidic chip 20 is delivered outside the detector 10. In this embodiment, the target position is the position where the amplification cavity 205a of the microfluidic chip 20 is inserted between the two temperature control modules 61 of the temperature control device 6.
[0248] The process by which the holding device 2 transports the microfluidic chip 20 into and out of the detector 10 is referred to as the inbound and outbound processes, respectively.
[0249] Figures 7-8 The structure of the holding device 2 in this embodiment is shown.
[0250] like Figure 7 and Figure 8 As shown, in this embodiment, the holding device 2 is movably disposed relative to the base 1 and includes a holding member 21, a support member 22, and a mounting block 23. Furthermore, in this embodiment, the detector 10 also includes a holding drive mechanism 26 and a holding detection device 27.
[0251] The retainer 21 is mounted on the support 22 and is used to connect with the microfluidic chip 20 to achieve the installation and fixation of the microfluidic chip 20 on the retainer 2. Specifically, as shown in the figure... Figure 7-8 as well as Figure 3 As shown, in this embodiment, the retaining member 21 is block-shaped, with two positioning blocks 211 on its top surface. These two positioning blocks 211 correspond one-to-one with the two positioning slots 202b on the base 202 of the microfluidic chip 20. The shape of each positioning block 211 is consistent with the shape of the corresponding positioning slot 202b, forming a polygon with curved and straight sides. In use, the microfluidic chip 20 is placed on the retaining member 21, and the two positioning blocks 211 are engaged in the two positioning slots 202b, thus achieving the installation and fixation of the microfluidic chip 20 on the retaining device 2, which is simple and convenient.
[0252] The support member 22 is located below the retaining member 21, is fixedly connected to the retaining member 21, and is mounted on the ultrasonic device 7 via the mounting block 23, so that the retaining member 21 is integrated into the ultrasonic device 7 and supported by the ultrasonic device 7. Figure 7 As shown, in this embodiment, the support member 22 is plate-shaped and generally U-shaped, with an opening 221 in the middle. The advantage of the opening 221 is that it exposes the reaction chamber 202a of the microfluidic chip 20 mounted on the retainer 21, allowing other modules to act on the reaction chamber 202a. For example, see [reference needed]. Figure 25During the nucleic acid extraction process, the magnet 81 of the magnetic attraction device 8 can pass through the opening 221 and attract the magnetic beads in the reaction chamber 202a.
[0253] The mounting block 23 is block-shaped and is fixed to the ultrasonic bracket 71 of the ultrasonic device 7. It is connected to the support member 22 via the guide rail of the linear guide slider 265 of the holding drive mechanism 26. Specifically, it is combined with... Figure 7 and Figure 25 As can be seen, in this embodiment, the holding device 2 includes two mounting blocks 23, which are fixedly connected to the two side frames of the ultrasonic support 71 (i.e., the first side frame 712 and the second side frame 713, which will be introduced later) respectively, and are both fixedly connected to the guide rail of the linear guide slider 265.
[0254] The holding drive mechanism 26 is driven by the holding member 21 and is used to drive the holding member 21 to move in the back-and-forth direction, so that the holding member 21 can drive the microfluidic chip 20 to or from the target position, completing the inbound and outbound process. Figure 7 As shown, in this embodiment, the holding drive mechanism 26 includes a holding motor 261, a holding transmission mechanism 262, and a linear guide slider 265. The holding transmission mechanism 262 includes a holding gear 263 and a holding rack 264. The holding motor 261 is fixed to the support plate 63 of the temperature control device 6 (see [reference]). Figure 20 The holding rack 264 meshes with the holding gear 263 and is connected to the guide rail of the linear guide slider 265. The slider of the linear guide slider 265 is fixed to the mounting block 23. Both the holding rack 264 and the guide rail of the linear guide slider 265 extend in the front-back direction. Thus, when the holding motor 261 rotates, it can drive the guide rail of the linear guide slider 265 to move back and forth through the holding gear 263 and the holding rack 264, so that the guide rail of the linear guide slider 265 drives the support member 22 and the holding member 21 to move back and forth, thereby realizing the front-back movement of the microfluidic chip 20, allowing the microfluidic chip 20 to reach or leave the target position through the front-back movement.
[0255] The holding detection device 27 is used to detect whether the holding member 21 has delivered the microfluidic chip 20 to the target position. See also Figure 7 and combined Figure 20 As can be seen, in this embodiment, the holding detection device 27 includes a holding detection element 271 and a holding trigger element 272. The holding trigger element 272 is mounted on the holding rack 264 and is specifically a baffle 275. The holding detection element 271 is mounted on the support plate 63 of the temperature control device 6 and is specifically a photoelectric switch 274 (in... Figure 20 (As shown in the figure). When the microfluidic chip 20 reaches the target position, the holding trigger 272 triggers the holding detection element 271 to send a signal, thereby realizing the detection of whether the microfluidic chip 20 has reached the target position.
[0256] During operation, when the holding detection device 27 detects that the holding member 21 has delivered the microfluidic chip 20 to the target position, the holding motor 261 stops rotating, so that the holding member 21 no longer moves forward, and the microfluidic chip 20 can stop at the target position.
[0257] As can be seen, the holding device 2 in this embodiment can not only hold the microfluidic chip 20, but also transport the microfluidic chip 20, so that the microfluidic chip 20 can reach or leave the target position.
[0258] Although the holding member 21 of the holding device 2 can fix the microfluidic chip 20, in order to further improve the placement stability of the microfluidic chip 20, such as Figures 9-10 As shown, in this embodiment, the detector 10 also includes a limiting member 28, which, together with the retaining member 21, completes the two-stage fixation of the microfluidic chip 20, effectively improving the installation stability of the microfluidic chip 20.
[0259] Depend on Figure 9 and Figure 10 As can be seen, in this embodiment, the limiting member 28 includes a connecting portion 281, an extension portion 282, and a locking portion 283. The connecting portion 281 and the locking portion 283 are respectively connected to the upper and lower ends of the extension portion 282, and extend backward and forward respectively, making the limiting member 28 generally Z-shaped. The connecting portion 281 is connected to the tray 63 of the temperature control device 6 (see...). Figure 20 The limiting member 28 is installed and fixed on the temperature control device 6. The snap-fit part 283 is used to insert into the slot 202c on the base 202 of the microfluidic chip 20 to apply pressure to the microfluidic chip 20 and press the microfluidic chip 20 onto the retaining member 21. In this way, the retaining device 2 can achieve initial positioning of the microfluidic chip 20 based on the snap-fit between the retaining member 21 and the microfluidic chip 20, while the limiting member 28 can achieve further fixation of the microfluidic chip 20 based on the snap-fit between the snap-fit part 283 and the microfluidic chip 20, so as to prevent the microfluidic chip 20 from accidentally shifting when subjected to the force of the ultrasonic device 7, etc., so as not to affect the normal operation of the microfluidic chip 20 by other modules, as well as the accuracy and consistency of detection.
[0260] Since the limiting member 28 is set on the temperature control device 6 and the holding device 2 moves back and forth relative to the temperature control device 6, the insertion and removal of the limiting member 28 in the slot 202c can be realized during the process of the holding device 2 moving in the back and forth direction to make the microfluidic chip 20 reach or leave the target position, which is simple and convenient.
[0261] When the microfluidic chip 20 needs to be placed into the container, the holding motor 261 moves the same number of steps as when it leaves the container, so that the holding device 2 transports the microfluidic chip 20 to the target position. During this process, the limiting member 28 is inserted into the slot 202c of the microfluidic chip 20, pressing the base 202 of the microfluidic chip 20, so that the microfluidic chip 20 is completely fixed and will not move accidentally.
[0262] Among them, such as Figure 9 and Figure 10 As shown, in this embodiment, a correction block 284 is provided on each of the two sides of the limiting member 28. Specifically, the two correction blocks 284 are provided on the left and right sides of the latching part 283. The two correction blocks 284 have the same structure, and their widths gradually increase from front to back, that is, their widths gradually decrease from back to front.
[0263] Since the direction from back to front is the direction in which the limiting member 28 is inserted into the card slot 202c, the width of both correction blocks 284 gradually narrows along the direction from back to front. This means that the width of both correction blocks 284 gradually decreases along the direction in which the limiting member 28 is inserted into the card slot 202c. In this way, during the insertion of the limiting member 28, the two correction blocks 284 can guide the limiting member 28 and prevent the limiting member 28 from deviating during the insertion process, so that the limiting member 28 can be inserted into the card slot 202c more smoothly, and the retaining member 21 can fix the microfluidic chip 20.
[0264] like Figure 8 As shown, in this embodiment, the retaining member 21 is provided with a clearance opening 212. Specifically, the retaining member 21 is provided with clearance openings 212 on both the front and rear sides. In this way, on the one hand, as Figure 9 As shown, the clearance opening 212 can allow the limiting member 28 to avoid interference between the limiting member 28 and the retaining member 21 during the insertion of the limiting member 28 into the slot 202c. On the other hand, as... Figure 25 As shown, the clearance port 212 can also allow the ultrasonic device 7 and the magnetic attraction device 8 to pass through, so as to facilitate the ultrasonic device 7 and the magnetic attraction device 8 to exert their effects on the reaction chamber 202a of the microfluidic chip 20.
[0265] Next, we will introduce the piercing component 101.
[0266] Figures 11-17 The structure of the piercing component 101 in this embodiment is shown.
[0267] like Figures 11-17As shown, in this embodiment, the puncture assembly 101 includes a puncture device 3, a prying mechanism 35, a rotary valve device 4, and a connecting device 5a for the pump assembly 5, so that the puncture assembly 101 integrates functions such as puncturing the sealing film, opening the temperature control device, controlling the rotary valve angle, and connecting the pump assembly to the microfluidic chip into one unit.
[0268] The piercing device 3, the opening mechanism 35, the rotary valve device 4, and the connecting device 5a are described here.
[0269] First, let's introduce the piercing device 3.
[0270] The piercing device 3 is used to pierce the sealing film and provides a mounting base for the opening mechanism 35, the rotary valve device 4 and the connecting device 5a, so that the opening mechanism 35, the rotary valve device 4 and the connecting device 5a are all integrated on the piercing device 3.
[0271] like Figures 11-14 As shown, in this embodiment, the puncture device 3 includes a puncture bracket 31, a puncture mechanism 32, a puncture driving mechanism 33, and a puncture detection device 34.
[0272] The puncture bracket 31 is mounted on the base 1 and supports the puncture mechanism 32, the puncture drive mechanism 33, and the puncture detection device 34. Specifically, as shown... Figures 11-14 As shown, in this embodiment, the piercing bracket 31 includes a first upright plate 311, a second upright plate 312, and a horizontal plate 313. The first upright plate 311 and the second upright plate 312 are arranged at intervals along the left-right direction, and their bottom ends are respectively fixed to the first side plate 12 and the second side plate 13 of the base 1 to realize the installation and fixation of the piercing device 3 on the base 1. The horizontal plate 313 is connected to the top of the first upright plate 311 and the second upright plate 312 and is used to support the piercing motor 331 of the piercing drive mechanism 33.
[0273] The piercing mechanism 32 is movably mounted on the piercing bracket 31 and includes a support plate 321 and a piercing element 322. The left and right ends of the support plate 321 are slidably connected to the first upright plate 311 and the second upright plate 312, respectively. The piercing element 322 is mounted on the support plate 321, so that when the support plate 321 moves vertically, it can drive the piercing element 322 to move vertically as well. Specifically, as... Figure 13As shown, both ends of the support plate 321 are connected to piercing sliders 323. The piercing sliders 323 are slidably mounted on the piercing guide rail 324, and the piercing guide rail 324 is fixed to the upright plate (i.e., the first upright plate 311 or the second upright plate 312), so that the support plate 321 is slidably connected to the upright plate through the guide rail slider mechanism. The piercing element 322 is fixed to the lower surface of the support plate 321 and is in the shape of a hollow cylinder, so that the piercing element 322 presses on the top cover 204 of the microfluidic chip 20, breaking the connecting rib 204d on the top cover 204 that connects the annular element 204h and the cover body 204g. Once all the connecting ribs 204d are broken, the annular part 204h can detach from the cover 204g, causing the piercing needle 204c to fall downwards and pierce the sealing film at the top of the storage cavity 201a of the microfluidic chip 20, thus connecting the storage cavity 201a with the atmosphere and achieving the piercing function.
[0274] As can be seen, based on the movable support plate 321 and the piercing member 322 disposed on the support plate 321, the piercing mechanism 32 has the function of piercing the sealing film, which facilitates the flow of fluid inside the microfluidic chip 20.
[0275] In addition to puncturing the sealing membrane, the puncture mechanism 32 can also reseal the storage cavity 201a.
[0276] Before the extraction step ends, the piercing needle 204c, under the contact action of the stop member 204e and the body 201, remains in the position of piercing the sealing membrane and connecting the storage cavity 201a to the atmosphere. During this process, the piercing member 322 does not break the rib 204f connecting the annular member 204h and the stop member 204e. After the extraction is completed and the fluid in the reaction cavity 202a has been transferred to the amplification member 205a, the piercing needle 204c can be used to pierce the sealing membrane. Driven by the support plate 321, the penetrating member 322 continues to press down on the annular member 204h, completely breaking the rib 204f connecting the annular member 204h and the stop member 204e. This causes the annular member 204h to drive the piercing needle 204c to move further toward the holding device 2 until the vent hole of the piercing needle 204c is blocked by the cover plate 206 of the microfluidic chip 20, thus resealing the storage cavity 201a to prevent accidental leakage of liquid in the storage cavity 201a, which would affect the normal operation of the detector 10.
[0277] As can be seen, the puncture mechanism 32 can achieve two-stage compression of the microfluidic chip 20, respectively meeting the requirements of puncturing the sealing film before extraction begins and resealing the storage cavity 201a after extraction ends.
[0278] The puncture drive mechanism 33 is mounted on the puncture bracket 31 and is used to drive the puncture mechanism 32 to move relative to the puncture bracket 31. Figures 13-14As shown, in this embodiment, the piercing drive mechanism 33 includes a piercing motor 331, a piercing gear 332, and a piercing rack 333. The piercing motor 331 is connected to the horizontal plate 313 and the second vertical plate 312 to achieve installation on the piercing bracket 31. The piercing motor 331 is driven by the piercing gear 332. The piercing gear 332 meshes with the piercing rack 333. The piercing rack 333 extends in the vertical direction and is connected to the support plate 321 of the piercing mechanism 32. Thus, when the piercing motor 331 rotates, the support plate 321 can be driven to move up and down through the piercing gear 332 and the piercing rack 333, thereby driving the piercing element 322 to move up and down, realizing the vertical movement of the piercing mechanism 32 relative to the piercing bracket 31, so that the piercing mechanism 32 moves away from or closer to the holding device 2, and in the process of approaching the holding device 2, the microfluidic chip 20 is subjected to two-stage compression.
[0279] The puncture detection device 34 is used to detect the position of the puncture mechanism 32. For example... Figures 11-14 As shown, in this embodiment, the puncture detection device 34 includes a first puncture detection element 341, a second puncture detection element 342, and a puncture trigger element 343. Both the first puncture detection element 341 and the second puncture detection element 342 are disposed on the first upright plate 311, and are arranged sequentially from top to bottom (i.e., the direction in which the puncture mechanism 32 approaches the holding device 2). That is, the first puncture detection element 341 is located above the second puncture detection element 342. The puncture trigger element 343 is disposed on the puncture mechanism 32. Specifically, the puncture trigger element 343 is disposed on the support plate 321 of the puncture mechanism 32, so that the puncture trigger element 343 can move together with the puncture mechanism 32. Exemplarily, both the first puncture detection element 341 and the second puncture detection element 342 are photoelectric switches 274, and correspondingly, the puncture trigger element 343 is a baffle 275.
[0280] During operation, the first puncture detection element 341 cooperates with the puncture trigger element 343 to detect whether the puncture mechanism 32 is in the initial position. The second puncture detection element 342 cooperates with the puncture trigger element 343 to form an opening detection mechanism 345, which detects whether the puncture mechanism 32 drives the disengaging mechanism 35 to the open position (i.e., the position where the disengaging mechanism 35 separates the two temperature control modules 61 of the temperature control device 6), to determine whether the two temperature control modules 61 have been opened by the disengaging mechanism 35.
[0281] It can be seen that, with the cooperation of the first puncture detection element 341, the second puncture detection element 342 and the puncture trigger element 343, the puncture detection device 34 can detect whether the puncture mechanism 32 has reached the initial position and the open position.
[0282] The puncture detection device 34 is used to detect whether the puncture mechanism 32 is in the initial position. On the one hand, it is convenient to determine whether the puncture mechanism 32 has been accurately reset after the detection is completed, so as to avoid affecting the smooth operation of the next operation due to the puncture mechanism 32 not being reset properly. On the other hand, it is also convenient to use the initial position as a reference and combine the setting of the working parameters of the puncture motor 331 to accurately control the puncture function and the connection between the rotary valve device 4 and the rotor 203a (specifically the valve stem 203b) of the microfluidic chip 20.
[0283] Specifically, before the detection process begins, the puncture detection device 34 determines whether the puncture mechanism 32 is in its initial position and determines the distance between the puncture component 322 and the microfluidic chip 20. Based on this, it obtains the number of rotations of the puncture motor 331 required to reach the breaking position (i.e., the position where the puncture mechanism 32 breaks the connecting rib 204d) from the initial position. Then, after the detection flow is started, the puncture motor 331 is controlled to rotate a preset number of times to puncture the sealing film. After that, based on the initial position, The distance between the valve component 41 (specifically the valve shaft 411) of the valve device 4 and the microfluidic chip 20 is determined, and the number of rotations of the puncture motor 331 required to connect the valve component 41 and the rotor 203a of the microfluidic chip 20 are obtained. After the sealing film is punctured, the puncture motor 331 is controlled to continue working until the corresponding number of rotations is reached, thus completing the connection between the valve component 41 and the rotor 203a, so that the valve component 41 can rotate the rotor 203a to realize the valve position switching of the microfluidic chip 20.
[0284] As can be seen, based on the puncture detection device 34 and the puncture motor 331, this embodiment can accurately control the puncture and the connection between the rotary valve device 4 and the microfluidic chip 20 simply by using the position information provided by the puncture detection device 34 and the parameter settings of the puncture motor 331. Since there is no need to set up additional detection components to detect the compression position and the connection position between the rotary valve device 4 and the microfluidic chip 20, the structure is relatively simple and the cost is low.
[0285] The advantage of using the puncture detection device 34 to detect whether the puncture mechanism 32 has reached the open position is that it is easy to determine whether the holding device 2 can be controlled to drive the microfluidic chip 20 to or from the target position.
[0286] In this embodiment, at the initial stage of the entire detection process, the holding device 2 controls the microfluidic chip 20 to move downward to the open position of the piercing mechanism 32, so that the separating mechanism 35 separates the two temperature control modules 61 before reaching the target position. That is, the piercing mechanism 32 drives the separating mechanism 35 to the separated position before the amplification cavity 205a reaches the target position. In other words, the microfluidic chip 20 is controlled to move to the target position with the holding device 2 only after the piercing detection device 34 detects that the piercing mechanism 32 has reached the open position, so that the amplification cavity 205a of the microfluidic chip 20 is inserted between the two temperature control modules 61. In this way, the amplification cavity 205a is inserted only when the two temperature control modules 61 are separated from each other, which can reduce wear during the insertion process.
[0287] In addition, in this embodiment, after the entire detection process is completed, the piercing mechanism 32 is first controlled to move upward to the open position, so that the separating mechanism 35 separates the two temperature control modules 61 again. Only then is the holding device 2 controlled to drive the microfluidic chip 20 to start leaving the target position. That is to say, the piercing mechanism 32 drives the separating mechanism 35 to the open position before the amplification cavity 205a starts to leave the target position. In other words, after the piercing detection device 34 detects that the piercing mechanism 32 has reached the open position, the holding device 2 is controlled to start to drive the microfluidic chip 20 to move outward and move out from between the two temperature control modules 61. In this way, the amplification cavity 205a moves outward only when the two temperature control modules 61 are separated from each other, which can reduce wear during the removal process and prevent residual liquid in the amplification cavity 205a from leaking and causing possible contamination.
[0288] It can be seen that by setting the opening mechanism 35 on the piercing mechanism 32 and equipping it with a piercing detection device 34 to detect whether the piercing mechanism 32 has reached the open position, the opening mechanism 35 can control the two temperature control modules 61 to open before the amplification chamber 205a is inserted and begins to be removed, so as to reduce the wear of the microfluidic chip 20 during the insertion and removal process.
[0289] Next, we will introduce the disengaging mechanism 35.
[0290] The separating mechanism 35 is used to separate the two temperature control modules 61 of the temperature control device 6 so that the amplification cavity 205a of the microfluidic chip 20 can be inserted and removed.
[0291] like Figure 13As shown, in this embodiment, the prying mechanism 35 is disposed on the piercing mechanism 32 and includes a rotating bearing 352 and a connecting shaft 353. The connecting shaft 353 is connected to the support plate 321 of the piercing mechanism 32. The rotating bearing 352 serves as the prying element 351, rotatably sleeved on the connecting shaft 353 and located on the rear side of the support plate 321, so as to apply force to the temperature control device 6 located on the rear side of the support plate 321. Specifically, in this embodiment, the rotating bearing 352 is a deep groove ball bearing.
[0292] Based on the above configuration, the rotating bearing 352 can move together with the piercing mechanism 32, and when it moves to the open position, see... Figure 22 Rotating bearing 352 separates the two temperature control modules 61; and when leaving the open position, see Figure 23 The function of the rotating bearing 352 on the temperature control device 6 disappears, and the two temperature control modules 61 re-attach to each other, or to the amplification cavity 205a inserted between them, so that the two temperature control modules 61 can be reset, or the amplification cavity 205a inserted between them can be temperature controlled.
[0293] As mentioned above, since the dispersing mechanism 35 is located on the piercing mechanism 32, the structure is more compact. There is no need to control the movement of the dispersing mechanism 35 separately, nor is there a need to set up a separate drive mechanism to drive the dispersing mechanism 35 to move. Therefore, the structure is simpler, the control is more convenient, the cost is lower, and the efficiency is higher.
[0294] Next, we will introduce the rotary valve device 4.
[0295] The rotary valve device 4 is used to rotate the switching valve 203 of the microfluidic chip 20 to sequentially control the reaction chamber 202a to switch between each storage chamber 201a and the amplification chamber 205a, thereby providing conditions for realizing the liquid flow control of the microfluidic chip 20.
[0296] like Figures 11-15 As shown, in this embodiment, the rotary valve device 4 includes a rotary valve component 41, a rotary valve bracket 42, a rotary valve drive mechanism 43, and an angle detection device 44.
[0297] The rotary valve 41 is used to connect with the rotor 203a of the switching valve 203 of the microfluidic chip 20 to drive the rotor 203a to rotate and realize valve position switching.
[0298] Combination Figure 12 , Figure 13 and Figure 15As can be seen, in this embodiment, the rotary valve component 41 is a rotary valve shaft 411, which rotatably passes through the support plate 321 of the piercing mechanism 32. Its upper end is constrained by the rotary valve bracket 42 fixed on the support plate 321, and its lower end passes through the piercing member 322 of the piercing mechanism 32. Thus, the rotary valve shaft 411 is rotatably mounted on the piercing mechanism 32. Bearings (not shown in the figure) are provided between the rotary valve shaft 411 and the rotary valve bracket 42, as well as between the rotary valve shaft 411 and the support plate 321, to facilitate the rotation of the rotary valve shaft 411.
[0299] In this embodiment, the rotary valve shaft 411 has an inner hole (not shown in the figure), so that the rotary valve shaft 411 can be fitted over the valve stem 203b of the microfluidic chip 20. Furthermore, the inner hole of the rotary valve shaft 411 is hexagonal, which matches the shape of the outer surface of the valve stem 203b. Therefore, after being fitted onto the valve stem 203b, the rotary valve shaft 411 and the valve stem 203b will not rotate relative to each other. Thus, the rotation of the rotary valve shaft 411 reliably drives the valve stem 203b to rotate, achieving valve position switching and allowing the liquid in the microfluidic chip 20 to flow sequentially.
[0300] Furthermore, in this embodiment, along the direction of the rotary valve shaft 411 near the holding device 2, the cross-sectional dimensions of one of the inner bore of the rotary valve shaft 411 and the valve stem 203b remain unchanged, while the other changes, so that the tightness of the connection between the rotary valve shaft 411 and the valve stem 203b increases along the direction of the rotary valve shaft 411 near the holding device 2. For example, the cross-sectional dimension of the inner bore of the rotary valve shaft 411 remains unchanged along the direction of the rotary valve shaft 411 near the holding device 2, while the cross-sectional dimension of the valve stem 203b increases along the direction of the rotary valve shaft 411 near the holding device 2 (i.e., from top to bottom), or the cross-sectional dimension of the valve stem 203b remains unchanged along the direction of the rotary valve shaft 411 near the holding device 2, while the cross-sectional dimension of the inner bore of the rotary valve shaft 411 decreases along the direction of the rotary valve shaft 411 near the holding device 2 (i.e., from top to bottom). Thus, when the rotary valve shaft 411 is initially fitted onto the valve stem 203b, the inner wall of the rotary valve shaft 411 does not fit tightly against the outer surface of the valve stem 203b, but rather has a gap. Subsequently, as the fitting depth increases, the connection tightness between the rotary valve shaft 411 and the valve stem 203b gradually increases. When the rotary valve shaft 411 is fully fitted onto the valve stem 203b, the connection tightness between the rotary valve shaft 411 and the valve stem 203b is at its maximum, and the two are relatively fixed. That is to say, as the piercing mechanism 32 moves the rotary valve shaft 411 closer to the microfluidic chip 20, the connection between the rotary valve shaft 411 and the valve stem 203b... The tightness of the connection between them gradually increases. On the one hand, this makes it easier to control the rotary valve 41 to be connected to the rotor 203a only after the puncture function is achieved, so as not to affect the smooth realization of the puncture function. On the other hand, it is also beneficial to play a certain corrective role for the microfluidic chip 20 in the event of misalignment. Even in extremely special cases, if the microfluidic chip 20 is misaligned before the rotary valve 41 is connected to the microfluidic chip 20, the cooperation between the rotary valve 41 and the valve stem 203b can be used to gradually straighten the microfluidic chip 20.
[0301] In addition, such as Figure 12 As shown, in this embodiment, the lower end of the rotary valve shaft 411 is lower than the lower end of the piercing member 322, and this arrangement is consistent with... Figures 2-4 As shown, the upper surface of the valve stem 203b of the microfluidic chip 20 is lower than the upper surface of the top cover 204 (i.e., the plane where the connecting rib 204d is located), which is adapted to the characteristic that the valve shaft 411 is sleeved on the valve stem 203b to realize the connection with the valve stem 203b.
[0302] Furthermore, in this embodiment, the lower end of the rotary valve shaft 411 is lower than the lower end of the piercing member 322, and less than the height of the upper surface of the valve stem 203b lower than the upper surface of the top cover 204. This ensures that when the piercing member 322 moves down to the breaking position and applies pressure to the upper surface of the top cover 204, breaking the connecting rib 204d, the rotary valve shaft 411 is not yet fitted onto the valve stem 203b. This facilitates the rotary valve shaft 411 being fitted onto the valve stem 203b only after the piercing function is achieved, thus completing the connection between the rotary valve device 4 and the rotor 203a, to prevent... The anti-rotation valve 41 is connected to the rotor 203a before the puncture function is realized, thereby avoiding the smooth realization of the puncture function due to the valve 41 being connected to the microfluidic chip 20 first and applying force to the microfluidic chip 20. On the other hand, the height of the lower end of the valve shaft 411 exceeding the lower end of the puncture member 322 is appropriate, neither too much nor too little. This makes it convenient for the valve shaft 411 to be fitted onto the valve stem 203b, and also prevents the valve shaft 411 from being too long, which would affect the realization of the two-stage clamping function of the puncture mechanism 32 on the microfluidic chip 20.
[0303] The rotary valve drive mechanism 43 is used to drive the rotary valve component 41 to rotate, so that the rotary valve component 41 drives the rotor 203a to rotate, thereby realizing valve position switching.
[0304] like Figure 15 As shown, in this embodiment, the rotary valve drive mechanism 43 includes a rotary valve motor 431 and a rotary valve transmission mechanism 432. The rotary valve motor 431 is driven to rotate the rotary valve component 41 (i.e., the rotary valve shaft 411) via the rotary valve transmission mechanism 432. Specifically, in this embodiment, both the rotary valve motor 431 and the rotary valve transmission mechanism 432 are mounted on the support plate 321 of the piercing mechanism 32. Furthermore, the rotary valve transmission mechanism 432 is a belt drive mechanism 433. The belt drive mechanism 433 includes a belt 436 and two pulleys 434. One of the two pulleys 434 is driven to rotate the rotary valve motor 431, and the other is driven to rotate the rotary valve component 41. The two are connected by the belt 436, enabling the belt drive mechanism 433 to achieve the drive connection between the rotary valve motor 431 and the rotary valve component 41. Thus, when the rotary valve motor 431 rotates, the rotary valve component 41 can be driven to rotate via the belt drive mechanism 433.
[0305] It is understandable that, in addition to being a belt drive mechanism 433, the rotary valve drive mechanism 432 can also be a chain drive mechanism or other drive mechanisms.
[0306] Referring again to 15, in this embodiment, the rotary valve drive mechanism 43 further includes a tensioning member 437, which is disposed on the piercing mechanism 32 and tensions the belt 436 of the belt drive mechanism 433 to prevent the belt 436 from becoming loose and affecting the smooth operation of the rotary valve. Specifically, in this embodiment, the tensioning member 437 includes a tensioning pin, which is disposed on the support plate 321. Of course, when the rotary valve drive mechanism 432 is a chain drive mechanism, the tensioning member 437 can also be provided and used to tension the chain of the chain drive mechanism.
[0307] The angle detection device 44 is used to detect the rotation angle of the rotary valve 41 to determine the rotary valve angle, realize accurate feedback of the rotary valve angle, form closed-loop control, and thus more accurately control the fluid to flow in the desired sequence.
[0308] like Figure 15 As shown, in this embodiment, the angle detection device 44 includes an angle detection element 441, a mounting base 443, and a magnet base 446. The angle detection element 441 includes a Hall magnet (not shown) and a Hall sensor 442. The Hall magnet is embedded in the magnet base 446, which is connected to the rotary valve 41, allowing the Hall magnet to rotate with the rotary valve 41. The Hall sensor 442 is mounted on the mounting base 443, which is fixed to the rotary valve bracket 42, preventing the Hall sensor 442 from rotating with the rotary valve 41. The Hall sensor 442 and the Hall magnet are directly opposite each other. Thus, when the rotary valve 41 rotates, the Hall sensor 442 can detect the rotation angle of the rotary valve 41 by detecting the rotation angle of the Hall magnet, thereby determining the rotary valve angle.
[0309] Since the rotary valve component 41, rotary valve bracket 42, rotary valve drive mechanism 43 and angle detection device 44 are all mounted on the piercing device 3, the rotary valve device 4 is mounted entirely on the piercing device 3, making the structure more compact. This helps to reduce the overall volume of the detector 10 and save the floor space occupied by the detector 10.
[0310] Furthermore, since the rotary valve 41 is mounted on the piercing mechanism 32, it moves together with the piercing mechanism 32 under the drive of the piercing drive mechanism 33. There is no need to control the movement of the rotary valve 41 separately, nor is there a need to equip the rotary valve 41 with a separate drive mechanism to drive its movement. Therefore, the structure is simpler, the control is more convenient, the cost is lower, and the efficiency is higher.
[0311] With the microfluidic chip 20 fixed, the valve angles corresponding to the connections between the storage chamber 201a and the reaction chamber 202a, and between the reaction chamber 202a and the amplification chamber 205a on the microfluidic chip 20 are fixed. Therefore, after the puncture mechanism 32 punctures the sealing membrane, controlling the rotation angle of the valve component 41, and cooperating with the pump assembly 5 to provide liquid flow power, can control the completion of different steps such as nucleic acid extraction and amplification.
[0312] Next, we will introduce the connecting device 5a.
[0313] The connecting device 5a is a component of the pump assembly 5 and is used to connect the drive pump 51 of the pump assembly 5 to the communication port 204b of the microfluidic chip 20, so that the drive pump 51 can drive the fluid in the microfluidic chip 20 to flow in a desired order by applying negative or positive pressure to the microfluidic chip 20.
[0314] like Figures 11-12 as well as Figures 16-17 As shown, in this embodiment, the connecting device 5a includes a connecting nozzle 52, a clamp 53, a constraint member 54, an elastic member 55, and a guide bearing 56.
[0315] The connecting nozzle 52 connects the drive pump 51 and the connecting port 204b. It is mounted on the support plate 321 of the piercing mechanism 32 and constrained by the clamp 53 to achieve the connection of the connecting nozzle 52 on the piercing mechanism 32. Specifically, in this embodiment, the connecting nozzle 52 is rod-shaped, with both its upper and lower ends passing through the clamp 53. The upper end extends above the support plate 321 for connection with the drive pump 51, while the lower end extends below the support plate 321 for connection with the connecting port 204b. The clamp 53 is connected to the support plate 321 by bolts or similar means to achieve the installation of the connecting nozzle 52 on the support plate 321. More specifically, as... Figure 12 As shown, in this embodiment, the connecting nozzle 52 is disposed on the front side of the support plate 321. At this time, the relative positional relationship between the connecting nozzle 52 and the support plate 321 is consistent with the relative positional relationship between the holding device 2 and the support plate 321, which makes it easier for the connecting nozzle 52 to connect to the connecting port 204b of the microfluidic chip 20 installed on the holding device 2.
[0316] Combination Figure 15 and Figure 16As can be seen, in this embodiment, the support plate 321 is provided with a first groove 326, and the clamp 53 is provided with a second groove 532. The first groove 326 and the second groove 532 are connected to form a closed groove, and the connecting nozzle 52 is embedded in the closed groove. Based on this, on the one hand, the installation effect of the connecting nozzle 52 is more stable and less likely to fall off; on the other hand, the position of the connecting nozzle 52 and the connecting port 204b of the microfluidic chip 20 at the target position are more consistent in the front-back direction, making it easier for the connecting nozzle 52 to be inserted into the connecting port 204b; furthermore, the connecting nozzle 52 does not completely protrude from the support plate 321 in the horizontal direction, occupying less space. Of course, as a variation, only the first groove 326 can be provided on the support plate 321, or only the second groove 532 can be provided on the clamp 53.
[0317] In addition, such as Figure 12 As shown, in this embodiment, the piercing member 322 is provided with a clearance opening 325, which faces the connecting mouth 52 to avoid interference with the connecting mouth 52. In this way, interference between the connecting mouth 52 and the piercing member 322 can be prevented while maintaining a relatively compact structure.
[0318] Since the connecting nozzle 52 is mounted on the piercing mechanism 32, the structure is more compact. Furthermore, the connecting nozzle 52 can move closer to or further away from the holding device 2 along with the piercing mechanism 32 under the drive of the piercing drive mechanism 33, connecting or separating from the microfluidic chip 20. There is no need to control the movement of the connecting nozzle 52 separately, nor is there a need to equip the connecting nozzle 52 with a separate drive mechanism to drive its movement. Therefore, the structure is simpler, the control is more convenient, the cost is lower, and the efficiency is higher.
[0319] The constraint member 54 and the elastic member 55 work together to adjust the vertical position of the connecting nozzle 52. (See also...) Figures 16-17 and combined Figure 11 and Figure 12In this embodiment, the constraint member 54 is plate-shaped, located below the support plate 321, and fixedly connected to the clamp 53. The connecting nozzle 52 passes through the constraint member 54. An elastic member 55 (e.g., spring 551) is fitted onto the connecting nozzle 52 and abuts against the limiting step 521 of the constraint member 54 and the connecting nozzle 52 to apply a downward elastic force to the connecting nozzle 52. The advantages of this design are twofold. First, after the connecting nozzle 52 is connected to the connecting port 204b, the elastic element 55 can apply a certain pressure to the connecting nozzle 52, increasing the connection strength and preventing the connecting nozzle 52 from accidentally disengaging. Second, the elastic element 55 allows the connecting nozzle 52 a certain amount of room to move, enabling it to move up and down to a certain extent when subjected to external force, thus adjusting its position. If, due to unforeseen circumstances, the connecting nozzle 52 and the connecting port 204b are not aligned vertically during connection, and the connecting nozzle 52 cannot be smoothly inserted into the connecting port 204b, the connecting nozzle 52 can move up and down to a certain extent under the action of the elastic element 55, preventing damage from hard contact with the microfluidic chip 20. In case of abnormal situations, the connecting nozzle 52 can be protected by damaging the elastic element 55.
[0320] A guide bearing 56 is fitted onto the connecting nozzle 52 to guide its vertical movement. Specifically, in this embodiment, the guide bearing 56 is a linear bearing, which is embedded in the second groove 532 and corresponding grooves on the rotary valve bracket 42. The guide bearing 56, together with the elastic element 55, guides the connecting nozzle 52 to move more accurately in the vertical direction relative to the piercing mechanism 32, so as to prevent the connecting nozzle 52 from deviating during its vertical movement relative to the piercing mechanism 32, thus affecting the smooth connection between the connecting nozzle 52 and the connecting port 204b.
[0321] As mentioned above, by setting the disengaging mechanism 35, the rotary valve device 4, and the connecting nozzle 52 on the piercing mechanism 32, the disengaging mechanism 35, the rotary valve device 4, and the connecting nozzle 52 can move together with the piercing mechanism 32, which can effectively simplify the structure and control process of the detector 10, reduce the volume of the detector 10, and improve the efficiency of the detector 10.
[0322] Next, we will introduce pump assembly 5.
[0323] Pump assembly 5 is used to drive the flow of liquid within microfluidic chip 20 to complete nucleic acid extraction and nucleic acid amplification steps.
[0324] As previously described, in this embodiment, the pump assembly 5 includes a drive pump 51 and a connecting device 5a. Since the connecting device 5a has already been described, this section mainly describes the structure of the drive pump 51.
[0325] Figure 18 and Figure 19The structure of the drive pump 51 is shown.
[0326] like Figure 18 and Figure 19 As shown, in this embodiment, the driving pump 51 is an injection pump, which includes a support device 518, a cylinder 511, a piston rod 512, a piston driving mechanism 513, a guide rod 514, a piston detection device 517, a connecting pipe 519, and a pipe joint 519a.
[0327] Among them, the support device 518 is used to support the piston rod 512, etc. Figure 18 and Figure 19 As shown, in this embodiment, the support device 518 includes a fixed plate 518a, a baffle 518b, a sliding plate 518c, and a sealing plate 518d. The fixed plate 518a is fixed to the ultrasonic bracket 71 of the ultrasonic device 7, which will be mentioned later. The baffle 518b is fixed to the fixed plate 518a. The sliding plate 518c is slidably disposed on the fixed plate 518a and located on the side of the baffle 518b near the cylinder 511, for supporting the piston rod 512 and guide rod 514, etc. The sealing plate 518d is fixed to the fixed plate 518a and located on the side of the sliding plate 518c near the cylinder 511, such that the sliding plate 518c is located between the baffle 518b and the sealing plate 518d.
[0328] The cylinder 511 and piston rod 512 cooperate to achieve air intake and exhaust, thereby applying negative or positive pressure to the microfluidic chip 20, causing the liquid in the microfluidic chip 20 to flow sequentially. Among them, the liquid... Figure 19 It is known that the cylinder 511 is provided with a piston hole 511a for the piston rod 512 to be inserted. The piston rod 512 is inserted into the piston hole 511a and can extend and retract relative to the cylinder 511 to compress the air in the piston hole 511a or draw air into the piston hole 511a for intake or exhaust. Specifically, the first end of the piston rod 512 is fixed to the sliding plate 518c, while the second end of the piston rod 512 passes through the sealing pressure plate 518d and is inserted into the piston hole 511a, so that when the sliding plate 518c slides, it can drive the piston rod 512 to slide in the piston hole 511a for intake or exhaust.
[0329] The piston drive mechanism 513 is driven by the piston rod 512 to extend and retract the piston rod 512 relative to the cylinder 511, thereby driving the liquid in the microfluidic chip 20. Figure 19As shown, in this embodiment, the piston drive mechanism 513 includes a lead screw motor 513a and a first bearing 513e. The lead screw motor 513a is a mechanism that converts the rotational motion of a motor into linear motion based on the cooperation of a lead screw and a nut. It includes a motor 513b, a lead screw 513c, and a nut 513d. The motor 513b is mounted on a sealing plate 518d. The lead screw 513c is connected to the motor 513b and passes through the sealing plate 518d and a sliding plate 518c. The nut 513d is sleeved on the end of the lead screw 513c that passes through the sliding plate 518c and is fixedly connected to the sliding plate 518c, so that when the motor 513b rotates, it can drive the sliding plate 518c to move through the lead screw 513c and the nut 513d, thereby driving the piston rod 512 to extend and retract. The first bearing 513e is sleeved on the end of the lead screw 513c that passes through the sliding plate 518d and is supported by a baffle 518b. Among them, the first bearing 513e is a deep groove ball bearing.
[0330] Guide rod 514 is used to guide piston rod 512. For example... Figure 19 As shown, in this embodiment, the first end of the guide rod 514 is fixed to the sliding plate 518c, while the second end passes through the sealing pressure plate 518d and is inserted into the connecting hole 511b of the cylinder 511. A second bearing 514a is provided in the connecting hole 511b. The second bearing 514a is clearance-fitted with the connecting hole 511b. Exemplarily, the second bearing 514a is a graphite bearing.
[0331] Under the guidance of the guide rod 514, the piston rod 512 is less likely to deviate during movement. This helps prevent the piston rod 512 from being damaged due to deviation, and also helps the drive pump 51 to drive the liquid flow in the microfluidic chip 20 more accurately.
[0332] The piston detection device 517 is used to detect the position of the piston rod 512 in order to control the piston drive mechanism 513. Figure 18 and Figure 19 As shown, in this embodiment, the piston detection device 517 includes a piston detection element 517a and a piston trigger element 517b. The piston detection element 517a is disposed at the end of the fixed plate 518a near the cylinder 511. The piston trigger element 517b is disposed on the sliding plate 518c. Thus, the piston trigger element 517b can move closer to or further away from the piston detection element 517a as the piston rod 512 extends and retracts. Exemplarily, the piston detection element 517a and the piston trigger element 517b are a photoelectric switch 274 and a baffle 275, respectively.
[0333] When the piston trigger 517b reaches the piston detector 517a, it triggers the piston detector 517a, causing it to send a signal to detect the position of the piston rod 512. In this embodiment, when the piston trigger 517b reaches the piston detector 517a, it indicates that the piston rod 512 has retracted to its final position. The air in the piston hole 511a is compressed to drive the liquid flow in the microfluidic chip 20. At this time, the lead screw motor 513a can be controlled to stop working, so that the piston rod 512 no longer retracts.
[0334] The connecting pipe 519 is used to connect the cylinder 511 to the connecting nozzle 52, thereby enabling the connection between the drive pump 51 and the connecting nozzle 52. Figure 19 As shown, in this embodiment, the connecting pipe 519 is a flexible hose and is connected to the cylinder 511 via a pipe fitting 519a. It should be noted that the connecting pipe 519 and the pipe fitting 519a are... Figure 1 and Figure 5 The middle part has been omitted.
[0335] To improve sealing, such as Figure 19 As shown, in this embodiment, the drive pump 51 includes a sealing ring 515 and a stud 516. The sealing ring 515 is disposed in the piston bore 511a to seal the piston bore 511a. The sealing ring 515 is blocked by the stepped surface inside the piston bore 511a. The stud 516 is threadedly connected to the piston bore 511a and presses against the sealing ring 515 to prevent the sealing ring 515 from loosening when the piston rod 512 moves. The piston rod 512 and the inner ring of the sealing ring 515 are interference-fitted to achieve a seal.
[0336] In addition, to improve sealing, in this embodiment, the pipe joint 519a and the cylinder 511 are sealed with thread sealant.
[0337] As can be seen, the drive pump 51 in this embodiment has a compact structure, small size, good sealing performance, and high operational reliability. It can drive the liquid flow in the microfluidic chip 20 relatively accurately, so that each step of the nucleic acid detection process can be carried out in an orderly manner.
[0338] The working process of the drive pump 51 in this embodiment is as follows:
[0339] In some cases, the motor 513b rotates in the forward direction, and the helical drive causes the sliding plate 518c, which is fixed to the nut 513d, to move to the right and approach the cylinder 511, driving the piston rod 512 to retract and compress the air in the piston hole 511a of the cylinder 511. The compressed air flows into the microfluidic chip 20 through the connecting pipe 419, driving the liquid flow in the microfluidic chip 20. When the piston rod 512 retracts to the end, causing the piston trigger 517b to reach the piston detection element 517a, the motor 513b stops running.
[0340] In other cases, the motor 513b reverses, the sliding plate 518c moves to the left, and the piston rod 512 extends, drawing air from the microfluidic chip 20 into the piston hole 511a of the cylinder 511. This air-drawing process can also drive the flow of liquid within the microfluidic chip 20.
[0341] Next, we will introduce the temperature control device 6.
[0342] 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 device 2, so as to provide suitable and stable temperature conditions for the amplification reaction and enable the amplification reaction to proceed smoothly.
[0343] Figures 20-21 The structure of the temperature control device 6 in this embodiment is shown.
[0344] like Figure 20 and Figure 21 As shown, in this embodiment, the temperature control device 6 includes a support plate 63, a pull plate 64, and two temperature control units 66. The two temperature control units 66 have the same structure and each includes a temperature control module 61, a sliding component 612, a support plate 65, and an opening mechanism 62, so that the temperature control device 6 includes two temperature control modules 61, two sliding components 612, two support plates 65, and two opening mechanisms 62.
[0345] The support plate 63 is fixed to the first side plate 12 and the second side plate 13 of the base 1 to support the two temperature control units 66.
[0346] The pull plate 64 is connected to two support plates 65 fixed on the support plate 63 to prevent the two temperature control modules 61 from not fitting together completely after the temperature control device 6 has been working for a long time.
[0347] Temperature control module 61 is used to control the temperature of amplification chamber 205a. Two temperature control modules 61 are disposed on tray 63 opposite to each other and movable relative to each other, and each includes heat exchange device 611 and heat dissipation device 613.
[0348] The heat exchange device 611 is used to exchange heat with the amplification chamber 205a, and to heat and cool the amplification chamber 205a so as to control the temperature of the amplification chamber 205a to cycle between a first temperature and a second temperature during the nucleic acid amplification process, so as to meet the requirements of nucleic acid amplification.
[0349] like Figure 20 and Figure 21As shown, in this embodiment, the heat exchange device 611 includes a thermoelectric cooler 611a, a heat transfer plate 611b, a first positioning member 611c, and a second positioning member 611d. The thermoelectric cooler 611a and the heat transfer plate 611b are arranged sequentially along a direction close to another heat exchange device 611 and are respectively embedded in the first positioning member 611c and the second positioning member 611d, and are fixed by the first positioning member 611c and the second positioning member 611d to achieve positioning of the thermoelectric cooler 611a and the heat transfer plate 611b. The first positioning member 611c and the second positioning member 611d are fixedly connected, allowing the thermoelectric cooler 611a and the heat transfer plate 611b to move together. The thermoelectric cooler 611a utilizes the Peltier effect for heating and cooling, achieving both heating and cooling. The heat transfer plate 611b is used to contact the amplification chamber 205a, and it is bonded to the thermoelectric cooler 611a via high-temperature silicone to achieve heat transfer between the thermoelectric cooler 611a and the amplification chamber 205a.
[0350] The heat dissipation device 613 is used to realize heat transfer between the heat exchange device 611 and the environment, thereby improving temperature control efficiency. For example... Figure 20 and Figure 21 As shown, in this embodiment, the heat dissipation device 613 is disposed on the side of the heat exchange device 611 away from the other temperature control module 61, and includes a heat sink 613a, a cooling fan 613b, a heat sink fixing member 613c, and a connecting block 613d. The cooling fan 613b contacts the heat exchange device 611 through the heat sink 613a. The heat sink 613a is mounted on the heat sink fixing member 613c and connected to the sliding assembly 612 through the connecting block 613d, so as to realize the movable arrangement of the heat dissipation device 613 and the heat exchange device 611 on the support plate 63.
[0351] The sliding component 612 connects to the corresponding support plate 65 and the temperature control module 61. For example... Figure 20 and Figure 21As shown, two support plates 65 are fixed to the tray 63 and are located outside their respective temperature control modules 61. The support plates 65 and the temperature control modules 61 are connected by a sliding assembly 612, allowing the two temperature control modules 61 to move away from each other when subjected to external force and to move closer together after the external force disappears. The sliding assembly 612 includes a temperature control elastic element 612a, a support shaft 612b, and a sliding guide mechanism 612c. The support shaft 612b connects the support plate 65 and the connecting block 613d. The temperature control elastic element 612a (e.g., a spring) is sleeved on the support shaft 612b and abuts against the support plate 65 and the connecting block 613d to apply an elastic force to the temperature control modules 61, bringing them closer together. The sliding guide mechanism 612c (e.g., a linear guide slider) is disposed on the tray 63 and connected to the connecting block 613d to guide the relative movement of the two temperature control modules 61. To improve the stability of the two temperature control modules 61, in this embodiment, the sliding assembly 612 includes two temperature control elastic elements 612a and two support shafts 612b. The two support shafts 612b of the same sliding assembly 612 are connected side by side between the temperature control module 61 and the support plate 65, and a temperature control elastic element 612a is sleeved on each support shaft 612b.
[0352] Initially, under the action of the temperature-controlled elastic element 612a, the two temperature-controlled modules 61 are attached together; specifically, the two heat transfer plates 611b are attached together. When the two temperature-controlled modules 61 are subjected to an outward pushing force, the two temperature-controlled modules 61 move away from each other and separate. During this process, the two temperature-controlled elastic elements 612a are compressed and store elastic force. When the outward pushing force disappears, the two temperature-controlled elastic elements 612a release the elastic force, causing the two temperature-controlled modules 61 to move closer together. At this time, if there is no object (such as the amplification element 205) between the two heat transfer plates 611b, the two temperature-controlled modules 61 are reattached together. If the amplification element 205 has been inserted between the two heat transfer plates 611b, both temperature-controlled modules 61 are attached to the amplification cavity 205a to heat or cool the amplification cavity 205a.
[0353] Since the temperature control device 6 does not move in the front-back direction, the insertion and removal of the expansion component 205 between the two temperature control modules 61 are achieved by the front-back movement of the holding device 2.
[0354] Since the holding device 2 needs to move to realize the microfluidic chip entering and leaving the chamber, the temperature control device 6 is set not to move in the direction of entering and leaving the chamber. Instead, the microfluidic chip 20 is inserted and removed between the two temperature control modules 61 by directly relying on the movement of the holding device 2 in the direction of entering and leaving the chamber. This is simple and convenient, and can eliminate the need for a drive mechanism to drive the temperature control device 6 to move in the direction of entering and leaving the chamber.
[0355] The opening mechanism 62 is used in conjunction with the previously described opening mechanism 35 to pre-separate the two temperature control modules 61 before the amplification element 205 is inserted or removed, thereby reducing the difficulty of inserting or removing the amplification element 205, reducing wear on the amplification element 205 during insertion and removal, and preventing liquid leakage.
[0356] like Figure 20 and Figure 21 As shown, in this embodiment, the two opening mechanisms 62 are connected to the two temperature control modules 61 in a one-to-one correspondence. Furthermore, the two opening mechanisms 62 are opposite to each other and have the same structure, each including an opening member 621, a reset elastic member 623, and a shaft 624.
[0357] The opening component 621 is used to contact the disengaging mechanism 35, and under the action of the disengaging mechanism 35, it drives the connected temperature control module 61 away from the other temperature control module 61, thereby separating the two temperature control modules 61. Figure 20 and Figure 21 As shown, in this embodiment, the opening member 621 is mounted on the heat exchange device 611 of the temperature control module 61, specifically fixed to the heat sink fixing member 613c of the heat exchange device 611, so that when the opening member 621 is pushed outward, it can drive the temperature control module 61 to move outward, realizing the separation of the two temperature control modules 61. The surface of the opening member 621 facing the other opening member 621 has a protrusion 622, which is arc-shaped and located between the upper and lower ends of the opening member 621. The protrusion 622 protrudes from the portions of the opening member 621 located on its upper and lower sides. Thus, the opening element 621 contacts the disengaging mechanism 35 through the protrusion 622, which facilitates the disengaging mechanism 35 to apply a pushing force to the opening element 621, causing the two opening elements 621 to move the two temperature control modules 61 away from each other and separate the two temperature control modules 61. However, before the disengaging mechanism 35 reaches the protrusion 622, or after it has passed the protrusion 622, the disengaging mechanism 35 no longer applies a pushing force to the opening element 621, which facilitates the two opening elements 621 to reset under the action of the reset elastic element 623, causing the two temperature control modules 61 to move closer to each other and re-fit together, or to fit together with the amplification chamber 205a.
[0358] A reset elastic element 623, fitted onto a shaft 624, applies an elastic force to the opening element 621, bringing the two opening elements 621 closer together. The shaft 624 is connected at both ends to a support plate 65 and the opening element 621, respectively. A step is provided on the shaft 624 to block the reset elastic element 623, causing it to abut against the step of the shaft 624 and the opening element 621, thus applying an elastic force to the opening element 621 to bring the two opening elements 621 closer together. As an example, the reset elastic element 623 is a spring 551.
[0359] When the disengaging mechanism 35 applies a pushing force to the two opening members 621, the two reset elastic members 623 increase in compression as the two opening members 621 move further apart, storing elastic energy. Then, when the disengaging mechanism 35 continues to move downward and the pushing force disappears, the two reset elastic members 623 release the stored elastic energy, pushing the two opening members 621 closer to each other.
[0360] Because the surface of the opening member 621 that contacts the disengaging mechanism 35 is arc-shaped, it can better cooperate with the rotating bearing 352 of the disengaging mechanism 35 to achieve the corresponding opening function. Furthermore, the arc-shaped surfaces on both sides of the most protruding portion of the protrusion 622 of the opening member 621 can also guide the rotating bearing 352 as it moves with the piercing mechanism 32, facilitating its smooth arrival at the most protruding portion of the protrusion 622.
[0361] At work, such as Figure 22 As shown, when the piercing mechanism 32 moves down to the position of the protrusion 622 of the opening member 621, the rotating bearing 352 of the disengaging mechanism 35 provided on the piercing mechanism 32 will push the two opening members 621 apart, causing the two opening members 621 to drive the two temperature control modules 61 to separate, making it easier for the amplification cavity 205a of the microfluidic chip 20 to be inserted between the heat transfer plates 611b of the two temperature control modules 61; and as Figure 23 As shown, when the piercing mechanism 32 continues to move downwards, and the rotating bearing 352 of the disengaging mechanism 35 reaches below the protrusion 622, the two temperature control modules 61 and the two opening pieces 621 approach each other under the action of the temperature control elastic element 612a and the reset elastic element 623, until the heat transfer plates 611b of the two temperature control modules 61 are in contact with the amplification cavity 205a inserted therein. Under the action of the temperature control elastic element 612a and the reset elastic element 623, the two temperature control modules 61 can fit more tightly with the amplification cavity 205a, which is beneficial to achieving better temperature control effect and improving temperature control efficiency.
[0362] It is evident that the designed opening mechanism 62 facilitates the implementation of the opening function.
[0363] Next, we will introduce the ultrasonic device 7.
[0364] The ultrasonic device 7 is used to apply ultrasonic excitation to the reaction chamber 202a of the microfluidic chip 20 to assist nucleic acid extraction.
[0365] Figure 24 The structure of the ultrasonic device 7 in this embodiment is shown.
[0366] like Figure 24As shown, in this embodiment, the ultrasonic device 7 is disposed on the base 1 and includes an ultrasonic bracket 71, an ultrasonic transducer 72, a support member 76, a pressure sensor 74, a connector 78, a blocking member 77, an ultrasonic drive mechanism 73, and an ultrasonic detection device 75.
[0367] The ultrasonic support 71 is mounted on the base plate 11 of the base 1 and includes a base frame 711, a first side frame 712, and a second side frame 713. The base frame 711 is fixedly connected to the base plate 11. The first side frame 712 and the second side frame 713 are connected to the left and right ends of the base frame 711. Figure 24 and Figure 5 As can be seen, in this embodiment, the ultrasonic support 71 is located between the transformer 16 and the ultrasonic generator 17 in the left-right direction, in front of the temperature control device 6 in the front-back direction, and below the holding device 2 in the vertical direction. Figure 25 As shown, the top ends of the first side frame 712 and the second side frame 713 are connected to the two mounting blocks 23 of the holding device 2 to support the ultrasonic support 71 for the holding device 2. Meanwhile, as... Figure 24 As shown, both the first side frame 712 and the second side frame 713 are equipped with ultrasonic slide rails 714 and ultrasonic sliders 715. The ultrasonic slide rails 714 are fixed to the first side frame 712 and the second side frame 713. Each ultrasonic slide rail 714 is equipped with two ultrasonic sliders 715, which are slidably connected to the ultrasonic slide rail 714 and arranged side by side in the vertical direction to connect with the support member 76 and the connector 78 respectively, thereby guiding the ultrasonic transducer 72 and the pressure sensor 74 to move up and down.
[0368] The ultrasonic transducer 72 is slidably connected to the ultrasonic support 71 via the support member 76 to move closer to or further away from the reaction chamber 202a. During the process of approaching the reaction chamber 202a, it contacts the reaction chamber 202a and applies vibration excitation. For example... Figure 24As shown, in this embodiment, the left and right ends of the support member 76 are respectively connected to the ultrasonic slider 715 located on the upper part of the first side frame 712 and the second side frame 713, so that the ultrasonic transducer 72 can move up and down along the ultrasonic slide rail 714. The ultrasonic transducer 72 is mounted on the support member 76 and passes through the support member 76, so that the ultrasonic head 721 of the ultrasonic transducer 72 is located above the support member 76, and the lower end of the ultrasonic transducer 72 is located below the support member 76, so that the ultrasonic head 721 and the lower end of the ultrasonic transducer 72 can contact the reaction chamber 202a and the pressure sensor 74 respectively. As the ultrasonic transducer 72 approaches the holding device 2, the ultrasonic head 721 of the ultrasonic transducer 72 passes through the opening 221 on the support member 22 and the holding member 21 of the holding device 2, and contacts the outer wall of the reaction chamber 202a of the microfluidic chip 20 located on the holding member 21, applying vibration excitation to the reaction chamber 202a to perform ultrasonic lysis, and promote the mixing of magnetic beads and reagents, so that the nucleic acid extraction process can be carried out more efficiently and smoothly.
[0369] Pressure sensor 74 is used to detect the magnitude of the pressure applied by ultrasonic transducer 72 to reaction chamber 202a. It is positioned below ultrasonic transducer 72 and is slidably connected to ultrasonic support 71 via connector 78 to move closer to or further away from ultrasonic transducer 72. Figure 24 As shown, in this embodiment, the left and right ends of the connector 78 are respectively connected to the ultrasonic slider 715 at the lower part of the first side frame 712 and the second side frame 713, so that the pressure sensor 74 can move up and down along the ultrasonic slide rail 714. The pressure sensor 74 is disposed on the connector 78 and moves up and down with the connector 78 to approach or move away from the ultrasonic transducer 72. During the process of approaching the ultrasonic transducer 72, it contacts the ultrasonic transducer 72 and pushes the ultrasonic transducer 72 upward until the pressure of the ultrasonic transducer 72 against the microfluidic chip 20 reaches the set value, so as to control the pressure of the ultrasonic transducer 72 on the microfluidic chip 20 to meet the requirements.
[0370] A blocking element 77 is disposed on the ultrasonic support 71 and is used to block the ultrasonic transducer 72 as it moves downward together with the pressure sensor 74, thereby preventing the pressure sensor 74 from being continuously compressed and thus shortening its service life. Figure 24 As shown, in this embodiment, the blocking member 77 is disposed on the second side frame 713 and located above the connector 78, at the lower limit position of the ultrasonic transducer 72 (which is also the initial position of the ultrasonic transducer 72).
[0371] The ultrasonic drive mechanism 73 is driven to connect with the connector 78, thereby driving the connector 78 to move the pressure sensor 74 up and down, which in turn drives the ultrasonic transducer 72 to move up and down. Figure 24As shown, in this embodiment, the ultrasonic drive mechanism 73 includes an ultrasonic motor 731, an ultrasonic gear 732, and an ultrasonic rack 733. The ultrasonic rack 733 is connected to the connector 78 and meshes with the ultrasonic gear 732. The ultrasonic motor 731 is driven by the ultrasonic gear 732. Thus, when the ultrasonic motor 731 rotates, it can drive the connector 78 to move up and down through the ultrasonic gear 732 and the ultrasonic rack 733, causing the connector 78 to move the pressure sensor 74 up and down, thereby driving the ultrasonic transducer 72 to move up and down. Therefore, in this embodiment, the ultrasonic drive mechanism 73 drives the ultrasonic transducer 72 to move up and down by driving the pressure sensor 74 to move up and down.
[0372] The ultrasonic testing device 75 is used to detect the position of the pressure sensor 74. For example... Figure 24 As shown, in this embodiment, the ultrasonic detection device 75 includes an ultrasonic detection element 751 and an ultrasonic trigger element 752. The ultrasonic detection element 751 is fixed to the first side frame 712 and is a photoelectric switch 274. The ultrasonic trigger element 752 is fixed to the connector 78 and is a baffle 275. The ultrasonic detection element 751 and the baffle 275 cooperate to detect whether the pressure sensor 74 has returned to its initial position, so as to determine whether the ultrasonic device 7 has been reset.
[0373] During operation, when the ultrasonic motor 731 rotates in the forward direction, the pressure sensor 74 moves upward under the action of the gear rack. After reaching the ultrasonic transducer 72, it drives the ultrasonic transducer 72 to move upward until the pressure sensor 74 detects that the pressure of the ultrasonic head 721 against the microfluidic chip 20 reaches the set value, at which point the ultrasonic motor 731 stops rotating. When the ultrasonic motor 731 rotates in the reverse direction, the pressure sensor 74 and the ultrasonic transducer 72 move downward. When they reach the position of the blocking member 77, the ultrasonic transducer 72 is blocked by the blocking member 77 and no longer moves downward, while the pressure sensor 74 continues to move downward. This separates the pressure sensor 74 from the ultrasonic transducer 72. When the ultrasonic trigger member 752 reaches the position of the ultrasonic detection member 751, the ultrasonic motor 731 stops rotating, causing the pressure sensor 74 to stop moving downward and remain at the initial position.
[0374] Next, we will introduce the magnetic attraction device 8.
[0375] The magnetic adsorption device 8 is used to adsorb magnetic beads in the reaction chamber 202a to achieve the purpose of separating nucleic acid from impurities such as proteins and separating nucleic acid from magnetic beads, facilitating the discharge of waste liquid during nucleic acid extraction and the transfer of extracted nucleic acid to the amplification chamber 205a.
[0376] Figure 25 The structure of the magnetic attraction device 8 in this embodiment is shown.
[0377] like Figure 25As shown, in this embodiment, the magnetic attraction device 8 is disposed on the ultrasonic support 71 and includes a magnet 81, a magnetic attraction driving mechanism 82, a magnetic attraction support 83 and a magnetic attraction detection device 84.
[0378] Among them, magnet 81 is used to attract magnetic beads in reaction chamber 202a. For example... Figure 25 As shown, in this embodiment, the magnet 81 is located in front of the ultrasonic transducer 72, mounted on a magnetic support 83, and driven by the magnetic drive mechanism 82 via the magnetic support 83. Under the drive of the magnetic drive mechanism 82, it moves between a non-magnetic position and a magnetic position. In the non-magnetic position, the magnet 81 is far from the reaction chamber 202a and does not apply magnetic attraction to the magnetic beads in the reaction chamber 202a. In the magnetic position, the magnet 81 is close to the reaction chamber 202a and applies magnetic attraction to the magnetic beads in the reaction chamber 202a. Based on this, the magnetic device 8 can be controlled to only attract magnetic beads when needed, such as when draining waste liquid or transferring nucleic acid to the amplification chamber 825a. This allows for the smooth separation of nucleic acid from other substances when needed, and also enables other processes such as cell lysis to proceed smoothly.
[0379] The magnetic drive mechanism 82 is driven by the magnetic support 83 and is mounted on the ultrasonic support 71. It includes a magnetic motor 821. The magnetic motor 821 is a linear motor connected to the first side frame 712 and the second side frame 713 of the ultrasonic support 71, and its output shaft is connected to the magnetic support 83. Thus, the magnetic motor 821 drives the magnetic support 83 to move the magnet 81 up and down, closer to or away from the holding device 2. As the magnet 81 approaches the holding device 2, it passes through the opening 221 on the support member 22 and the holding member 21, thereby exerting an attractive force on the magnetic bead within the reaction chamber 202a of the microfluidic chip 20 located on the holding member 21.
[0380] The magnetic attraction detection device 84 is used to detect the position of the magnet 81 to determine whether the magnet 81 has reached the magnetic attraction position or returned to the non-magnetic attraction position. Figure 25As shown, in this embodiment, the magnetic attraction detection device 84 includes a first magnetic attraction detection element 841, a second magnetic attraction detection element 842, and a magnetic attraction trigger element 843. The first magnetic attraction detection element 841 and the second magnetic attraction detection element 842 are fixedly connected to the ultrasonic support 71, and are arranged alternately in a top-to-bottom direction (i.e., the direction in which the magnet 81 moves away from the microfluidic chip 20). The magnetic attraction trigger element 843 is fixed to the magnetic attraction support 83 to move with the magnet 81. When the magnetic attraction trigger element 843 reaches the position of the first magnetic attraction detection element 841, it indicates that the magnet 81 has reached the magnetic attraction position. When the magnetic attraction trigger element 843 reaches the position of the second magnetic attraction detection element 842, it indicates that the magnet 81 has returned to the non-magnetic attraction position. Specifically, the first magnetic attraction detection element 841 and the second magnetic attraction detection element 842 are photoelectric switches 274, and the magnetic attraction trigger element 843 is a baffle 275.
[0381] During operation, when the magnetic motor 821 operates in the forward direction, its output axis moves upward, causing the magnetic support 83 to move upward, which in turn causes the magnet 81 and the magnetic trigger 843 to move upward. When the magnetic trigger 843 reaches the first magnetic detection element 841, the magnetic motor 821 stops working. At this time, the magnet 81 reaches the magnetic attraction position and applies a magnetic attraction force to the magnetic beads in the reaction chamber 202a of the microfluidic chip 20, thereby attracting and aggregating the magnetic beads. When the magnetic motor 821 operates in the reverse direction, its output axis moves downward, causing the magnetic support 83 to move downward, which in turn causes the magnet 81 and the magnetic trigger 843 to move downward. When the magnetic trigger 843 reaches the second magnetic detection element 842, the magnetic motor 821 stops working. At this time, the magnet 81 reaches the non-magnetic attraction position and no longer attracts the magnetic beads. Therefore, it is convenient for the ultrasonic device 7 to mix the magnetic beads and reagents.
[0382] Next, we will introduce the detection device 91.
[0383] The detection device 91 is used to detect the target nucleic acid during the amplification process.
[0384] like Figure 5 As shown, in this embodiment, the detection device 91 is connected to the top of the second side plate 13 of the base 1 and is located behind the temperature control device 6.
[0385] like Figure 20 and Figure 21 As shown, in this embodiment, the detection device 91 is a rotating multi-channel fluorescence detection device, which includes an excitation fiber 911 and an emission fiber 912, used to emit excitation light into the amplification cavity 205a and to recover the excited light in the amplification cavity 205a for detection and analysis.
[0386] Furthermore, by Figure 20 and Figure 21As can be seen, in this embodiment, both the excitation fiber 911 and the emission fiber 912 extend between the two temperature control modules 61 of the temperature control device 6, so as to transmit light between them and the amplification cavity 205a in which the amplification reaction is carried out between the two temperature control modules 61.
[0387] Next, we will introduce the monitoring device 92.
[0388] The monitoring device 92 is installed on the base 1 and is used to acquire information about the storage container containing the sample to be added to the storage cavity 201a of the microfluidic chip 20, acquire the detection item information of the microfluidic chip 20, monitor the reaction in the microfluidic chip 20, and alarm for abnormal situations.
[0389] Figure 26 The structure of the monitoring device 92 is shown.
[0390] like Figure 26 As shown, in this embodiment, the monitoring device 92 includes a first barcode scanner 921, a second barcode scanner 922, and a camera 923.
[0391] The first barcode scanner 921 is connected to the second side plate 13 of the base 1 and is located at a forward position on the second side plate 13. It is used to scan the barcode on the storage container (e.g., sample tube) containing the sample to be added to the storage cavity 201a to obtain sample information.
[0392] The second barcode scanner 922 is connected to the second side plate 13 of the base 1 and is located at a relatively rear position on the second side plate 13, behind the first barcode scanner 921. It is used to scan the barcode on the microfluidic chip 20 to obtain the detection item information of the microfluidic chip 20, thereby determining whether the microfluidic chip 20 is required for the detection item, so as to avoid the detection report being incorrect due to the operator picking up the wrong microfluidic chip 20.
[0393] Camera 923 is an infrared camera, which is connected to the first side plate 12 of the base 1. It is used to capture in real time whether the reagent or waste liquid is completely drawn into or discharged from the reaction chamber 202a, and to monitor the mixing of the reagent magnetic beads in the reaction chamber 202a in real time, so as to trigger an alarm when the situation is abnormal.
[0394] Based on the monitoring device 92, the progress of the inspection can be easily understood, ensuring that the entire inspection process can be carried out accurately and smoothly.
[0395] 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, the detection device 91, and the monitoring device 92, which can realize fully automated control of the entire nucleic acid detection process. In particular, since the rotary valve device 4, the opening mechanism 35, and the connecting device 5a are integrated on the piercing device 3 to form the piercing assembly 101, and the relative positional relationship and mutual movement relationship of the piercing assembly 101, the holding device 2, the temperature control device 6, the ultrasonic device 7, and the magnetic suction device 8 are reasonably designed, the structure is simple, the layout is compact, the size is small, and the efficiency is high.
[0396] 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:
[0397] (1) Add the sample into the microfluidic chip 20;
[0398] (2) Place the microfluidic chip 20 on the holding device 2 and touch the “Start” button on the display screen;
[0399] (3) After the test is completed, the microfluidic chip 20 is sent out of the cavity by the holding device 2, and the operator can take out the microfluidic chip 20.
[0400] 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.
[0401] The microfluidic chip loading process mainly includes the following two steps:
[0402] (1) Before testing, the first barcode scanner 921 scans the barcode of the storage container to obtain sample information, and the operator adds the sample into the microfluidic chip 20.
[0403] (2) During testing, the operator touches the "Out of Chamber" button on the display screen to make the holding motor 261 of the holding device 2 work, driving the holding part 21 to move outward into place. The operator then places the microfluidic chip 20 on the holding part 21 and touches the "Start" button on the display screen to make the holding motor 261 work in reverse, driving the microfluidic chip 20 to move backward to the target position inside the instrument to cooperate with other modules. This allows the limiting part 28 to be inserted into the slot 202c of the microfluidic chip 20 to press the microfluidic chip 20 firmly, thus achieving complete fixation of the microfluidic chip 20 and completing the loading of the microfluidic chip 20.
[0404] The nucleic acid extraction process mainly includes the following eight steps:
[0405] (3) During the movement of the microfluidic chip 20 toward the target position, the piercing motor 331 of the piercing component 101 works, driving the piercing mechanism 32 to move downward, and stops moving downward when the separating mechanism 35 on the piercing mechanism 32 separates the two temperature control modules 61 that were originally attached to the temperature control device 6, so that the amplification cavity 205a of the microfluidic chip 20 can enter between the two temperature control modules 61. After the microfluidic chip 20 is in place, the two temperature control modules 61 approach each other under the action of elasticity and automatically attach to the amplification cavity 205a.
[0406] (4) After the microfluidic chip 20 is in place, the second barcode scanner 922 scans the barcode on the microfluidic chip 20 to obtain the detection item information of the microfluidic chip 20;
[0407] (5) The piercing mechanism 32 continues to move downward, and the piercing part 322 crushes the connecting rib 204d between the connecting top cover 204 of the microfluidic chip 20 and the piercing needle 204c, causing the piercing needle 204c to fall and pierce 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.
[0408] (6) After the connecting rib 204d is broken, the piercing mechanism 32 continues to move downward until the rotary valve shaft 411 on the piercing mechanism 32 is fitted onto the valve stem 203b of the microfluidic chip 20, and the connecting nozzle 52 on the piercing mechanism 32 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. The rotary valve motor 431 of the rotary valve device 4 works, and the valve stem 203b is rotated according to a specific timing and angle through the belt drive mechanism 433 and the rotary valve shaft 411, so that different storage chambers 201a are switched to be connected to the reaction chamber 202a. When the storage chamber 201a is connected to the reaction chamber 202a, the fluid in the storage chamber 201a is drawn to the reaction chamber by the suction action of the drive pump 51. In cavity 202a, the reaction takes place; during the connection process between the rotary valve shaft 411 and the valve stem 203b and the connecting nozzle 52 and the connecting port 204b, although the piercing mechanism 32 presses on the annular part 204h, causing the rib 204f between the annular part 204h and the stop part 204e to deform to a certain extent, it does not completely break the rib 204f connecting the annular part 204h and the stop part 204e. Therefore, the stop part 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 part 204e does not cause the piercing mechanism 32 to be completely unable to move down, but the deformation of the rib 204f meets the corresponding downward movement requirements of the piercing mechanism 32.
[0409] (7) During the reaction, when the magnetic beads and reagents in the reaction chamber 202a need to be mixed, the ultrasonic motor 731 of the ultrasonic device 7 works, so that the ultrasonic transducer 72 presses against the outer wall of the reaction chamber 202a. By controlling the power, oscillation time and pressure applied to the reaction chamber 202a by the ultrasonic transducer 72, the magnetic beads and reagents are mixed to assist nucleic acid extraction.
[0410] (8) During the reaction, when the magnetic beads and reagents are mixed and the waste liquid needs to be discharged, the ultrasonic motor 731 works in reverse so that the ultrasonic transducer 72 moves away from the reaction chamber 202a. Then the magnetic motor 821 of the magnetic suction device 8 works so that the magnet 81 contacts the reaction chamber 202a and the magnetic beads are adsorbed 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.
[0411] (9) During the process of the ultrasonic device 7 and the magnetic suction device 8 acting on the reagent and magnetic beads in the reaction chamber 202a, the camera 923 continuously takes pictures of the reaction chamber 202a to monitor whether the reagent or waste liquid is completely sucked into or discharged from the reaction chamber 202a, and whether the reagent and magnetic beads have been mixed.
[0412] (10) After nucleic acid extraction is completed under the synergistic action of puncture component 101, ultrasonic device 7, magnetic suction device 8 and drive pump 51, firstly, rotary valve motor 431 works to drive valve rod 203b to rotate, connecting reaction chamber 202a and amplification chamber 205a, and under the squeezing action of drive pump 51, the nucleic acid extract flows into amplification chamber 205a. Then, puncture mechanism 32 continues to move down, breaking the rib 204f of microfluidic chip 20, so that the puncture needle 204c of microfluidic chip 20 and cover plate 26 together re-close storage chamber 201a, preparing for amplification and fluorescence detection.
[0413] 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 26, the rotary valve shaft 411 and the connecting nozzle 52 continue to move downwards along with the piercing mechanism 32. During this downward movement, the rotary valve shaft 411 and the connecting nozzle 52 will not be damaged. The connecting nozzle 52 can move up and down moderately under the action of the elastic element 55 to avoid damage, while the rotary valve shaft 411 can be strengthened by using higher-strength materials to prevent damage. Furthermore, since the liquid transfer steps in the entire detection process have already been completed during this downward movement, even if the continued downward movement of the rotary valve shaft 411 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 411 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.
[0414] Nucleic acid amplification and detection mainly include the following three processes:
[0415] (11) After the nucleic acid extraction solution flows into the amplification chamber 205a, the semiconductor cooling chip 611a of the temperature control device 6 starts circulating heating. The heat is transferred to the amplification chamber 205a through the heat transfer chip 611b, providing suitable and stable temperature conditions for nucleic acid amplification. During this process, the cooling fan 613b dissipates heat.
[0416] (12) While amplifying, the detection device 91 works, repeatedly switching the fluorescence detection channel to detect the excited fluorescence in the amplification chamber 205a in real time.
[0417] (13) After amplification and detection are completed, a detection report is generated and the detection record is stored.
[0418] The microfluidic chip 20 removal process mainly includes the following two steps:
[0419] (14) After the test is completed, the microfluidic chip is ejected from the chamber: First, the motors of the piercing component 101, the ultrasonic device 7 and the magnetic suction device 8 are activated, the piercing part 322, the ultrasonic transducer 72 and the magnet 81 move away from the microfluidic chip 20, the motor of the holding device 2 is activated, and the microfluidic chip 20 is moved outward to eject the chip. During this process, when the piercing mechanism 32 moves upward to the point where the opening mechanism 35 separates the two temperature control modules 61 again, the upward movement is paused, the motor of the holding device 2 starts up, and the microfluidic chip 20 begins to eject the chip. After the amplification chamber 205a is completely removed from the two temperature control modules 61, the piercing mechanism 32 continues to rise, so that the two temperature control modules 61 are reattached together.
[0420] (15) After the microfluidic chip 20 is in place, 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 operator touches the "enter the box" button on the display screen. When the retainer 21 reaches the starting position, it stops and the instrument sends a signal that it can be powered off. When the operator powers off, the detector 10 is turned off.
[0421] 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.
[0422] 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.
[0423] 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 detector (10), characterized in that, include: Base (1); A holding device (2) is disposed on the base (1) and is used to hold the microfluidic chip (20). The puncture device (3) includes a puncture mechanism (32) and a puncture drive mechanism (33) connected by a drive. The puncture drive mechanism (33) drives the puncture mechanism (32) to move relative to the base (1). During the movement of the puncture mechanism (32) relative to the base (1), the puncture needle (204c) is driven to move relative to the storage cavity (201a) of the microfluidic chip (20) to puncture the sealing film on the storage cavity (201a). A temperature control device (6) is disposed on the base (1) and includes two temperature control modules (61). The two temperature control modules (61) are opposite to each other and can move relative to each other. The two temperature control modules (61) control the temperature of the part (207) to be controlled when the part (207) of the microfluidic chip (20) is inserted between the two temperature control modules (61); and A separating mechanism (35) is movably disposed relative to the holding device (2) and separates the two temperature control modules (61) before the part to be temperature controlled (207) begins to move outward from between the two temperature control modules (61) so that the part to be temperature controlled (207) can move outward from between the two temperature control modules (61). The separating mechanism (35) is disposed on the piercing mechanism (32) and separates the two temperature control modules (61) as the piercing mechanism (32) moves.
2. The detector (10) according to claim 1, characterized in that, The temperature control device (6) includes two opening parts (621), which are connected to the two temperature control modules (61) in a one-to-one correspondence. The disengaging mechanism (35) separates the two temperature control modules (61) by pushing the two opening parts (621) away from each other.
3. The detector (10) according to claim 2, characterized in that, The opening member (621) includes a protrusion (622), and the disengaging mechanism (35) pushes the two opening members (621) away from each other by acting on the protrusion (622).
4. The detector (10) according to claim 2, characterized in that, The surface of the opening member (621) that contacts the disengaging mechanism (35) is arc-shaped.
5. The detector (10) according to claim 2, characterized in that, The temperature control device (6) includes a reset elastic element (623), which abuts against the opening element (621) and applies an elastic force to the opening element (621) to bring the two opening elements (621) closer to each other.
6. The detector (10) according to claim 1, characterized in that, The separating mechanism (35) includes a separating element (351), which is rotatably disposed, and the separating mechanism (35) separates the two temperature control modules (61) through the separating element (351).
7. The detector (10) according to claim 1, characterized in that, The disengaging mechanism (35) is movable up and down relative to the holding device (2), and the disengaging mechanism (35) separates the two temperature control modules (61) during the up and down movement.
8. The detector (10) according to claim 1, characterized in that, The holding device (2) includes a holding member (21), on which a positioning block (211) is provided. The positioning block (211) is used to engage with the positioning groove (202b) of the microfluidic chip (20) to fix the microfluidic chip (20).
9. The detector (10) according to claim 1, characterized in that, The detector (10) includes a limiting member (28) for inserting into the slot (202c) of the microfluidic chip (20) to press the microfluidic chip (20).
10. The detector (10) according to claim 9, characterized in that, The limiting member (28) is disposed on the temperature control device (6) so that it is inserted into the slot (202c) of the microfluidic chip (20) during the process of inserting the two temperature control modules (61) into the part to be temperature controlled (207).
11. The detector (10) according to claim 9, characterized in that, The limiting member (28) is provided with a correction block (284), and the width of the correction block (284) gradually decreases along the direction in which the limiting member (28) is inserted into the slot (202c).
12. The detector (10) according to claim 1, characterized in that, The holding device (2) is horizontally movable relative to the base (1), and the detector (10) includes a holding drive mechanism (26), which is drivenly connected to the holding device (2) to drive the holding device (2) to move horizontally, closer to or away from the temperature control device (6).
13. The detector (10) according to any one of claims 1-12, characterized in that, The piercing mechanism (32) pierces the sealing film on the storage cavity (201a) by breaking the connecting rib (204d) of the connecting piercing needle (204c) of the microfluidic chip (20).
14. The detector (10) according to claim 13, characterized in that, After the piercing needle (204c) pierces the sealing film, the piercing mechanism (32) further drives the piercing needle (204c) to move toward 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).
15. The detector (10) according to any one of claims 1-12, characterized in that, The detector (10) includes at least one of the following: The rotary valve device (4) includes a rotary valve component (41) and a rotary valve drive mechanism (43). The rotary valve component (41) is disposed on the piercing mechanism (32) and is connected or separated from the rotor (203a) of the switching valve (203) of the microfluidic chip (20) during the movement of the piercing mechanism (32). The rotary valve drive mechanism (43) is driven to connect with the rotary valve component (41) so as to drive the rotor (203a) to rotate when the rotary valve component (41) is connected to the rotor (203a) to realize the switching of the valve position of the switching valve (203). The pump assembly (5) includes a connecting nozzle (52) and a drive pump (51). The connecting nozzle (52) is disposed on the piercing mechanism (32) and connects or disconnects from the communication port (204b) of the microfluidic chip (20) as the piercing mechanism (32) moves. The drive pump (51) is connected to the connecting nozzle (52) to drive the fluid flow in the microfluidic chip (20) when the connecting nozzle (52) is connected to the communication port (204b).
16. The detector (10) according to claim 15, characterized in that, The rotary valve component (41) includes a rotary valve shaft (411), which is used to be sleeved on the valve stem (203b) of the rotor (203a) and drives the valve stem (203b) to rotate under the drive of the rotary valve drive mechanism (43) so as to realize the switching of the valve position of the switching valve (203).
17. The detector (10) according to claim 16, characterized in that, The inner hole of the rotary valve shaft (411) for engaging with the valve stem (203b) is a polygonal hole.
18. The detector (10) according to claim 16, characterized in that, Along the direction of the rotary valve shaft (411) toward the retaining device (2), the cross-sectional dimensions of one of the inner hole of the rotary valve shaft (411) and the valve stem (203b) remain unchanged, while the cross-sectional dimensions of the other change, so that the tightness of the connection between the rotary valve shaft (411) and the valve stem (203b) increases along the direction of the rotary valve shaft (411) toward the retaining device (2).
19. The detector (10) according to claim 15, characterized in that, The piercing mechanism (32) includes a piercing element (322). During the movement of the piercing element (322) relative to the base (1), it acts on the microfluidic chip (20), causing the piercing needle (204c) to move relative to the storage cavity (201a). The piercing element (322) is sleeved on the outside of the rotary valve (41).
20. The detector (10) according to claim 19, characterized in that, The end of the rotary valve (41) near the retaining device (2) protrudes from the end of the piercing member (322) near the retaining device (2).
21. The detector (10) according to claim 20, characterized in that, The distance between the end of the rotary valve (41) near the holding device (2) and the end of the piercing member (322) near the holding device (2) is less than the distance between the top of the rotor (203a) and the plane where the connecting rib (204d) of the microfluidic chip (20) is located.
22. The detector (10) according to claim 15, characterized in that, The pump assembly (5) includes a constraint member (54) and an elastic member (55). The constraint member (54) supports the connecting nozzle (52), and the elastic member (55) is sleeved on the outside of the connecting nozzle (52) and abuts against the constraint member (54) to apply an elastic force toward the connecting port (204b) to the connecting nozzle (52).
23. The detector (10) according to claim 15, characterized in that, The drive pump (51) includes a cylinder (511), a piston rod (512), and a piston drive mechanism (513). The piston rod (512) is retractably inserted into the cylinder (511). The piston drive mechanism (513) is drivenly connected to the piston rod (512) and drives the fluid flow in the microfluidic chip (20) by driving the piston rod (512) to extend and retract.
24. The detector (10) according to claim 23, characterized in that, The drive pump (51) includes a guide rod (514) which is connected to the cylinder (511) and guides the piston rod (512) during its movement.
25. The detector (10) according to any one of claims 1-12, characterized in that, The detector (10) includes at least one of the following: The ultrasonic device (7) includes an ultrasonic transducer (72) and an ultrasonic driving mechanism (73). The ultrasonic driving mechanism (73) drives the ultrasonic transducer (72) to move relative to the holding device (2). After the ultrasonic transducer (72) contacts the outer wall of the reaction chamber (202a) of the microfluidic chip (20), it transmits vibration to the reaction chamber (202a) of the microfluidic chip (20). The magnetic attraction device (8) includes a magnet (81) and a magnetic attraction driving mechanism (82). The magnetic attraction driving mechanism (82) drives the magnet (81) to move between a magnetic attraction position and a non-magnetic attraction position to control whether the magnet (81) attracts the magnetic material for attracting the target object in the reaction chamber (202a) of the microfluidic chip (20). The detection device (91) is set on the base (1) and detects the target material obtained by amplification in the amplification cavity (205a) of the microfluidic chip (20); A monitoring device (92) is disposed on the base (1) and is used to perform at least one of the following functions: acquiring information about the storage container containing the sample to be added to the storage cavity (201a) of the microfluidic chip (20), acquiring the detection item information of the microfluidic chip (20), monitoring the reaction in the microfluidic chip (20), and alarming for abnormal situations.
26. The detector (10) according to claim 25, characterized in that, The ultrasonic device (7) includes a pressure sensor (74) for detecting the pressure applied by the ultrasonic transducer (72) to the reaction chamber (202a). The pressure sensor (74) is located on the side of the ultrasonic transducer (72) away from the holding device (2) and is driven to be connected to the ultrasonic driving mechanism (73) so that it moves closer to and away from the ultrasonic transducer (72) under the drive of the ultrasonic driving mechanism (73). The ultrasonic driving mechanism (73) drives the ultrasonic transducer (72) to move by driving the pressure sensor (74) to move after the pressure sensor (74) contacts the ultrasonic transducer (72).
27. The detector (10) according to claim 26, characterized in that, The ultrasonic device (7) includes a blocking member (77) for blocking the ultrasonic transducer (72) as the pressure sensor (74) and the ultrasonic transducer (72) move away from the holding device (2) together, thereby separating the pressure sensor (74) from the ultrasonic transducer (72).
28. The detector (10) according to claim 25, characterized in that, The ultrasonic transducer (72) and / or the magnet (81) move in the up-down direction.
29. The detector (10) according to claim 25, characterized in that, The monitoring device (92) includes at least one of the following: A first barcode scanner (921) is used to scan the barcode on the storage container to obtain a sample; The second barcode scanner (922) is used to scan the barcode on the microfluidic chip (20) to obtain the detection item information of the microfluidic chip (20); A camera (923) is used to capture the reaction in the microfluidic chip (20).
30. A detection system (100) comprising a microfluidic chip (20), characterized in that, It also includes the detector (10) as described in any one of claims 1-29.
Citation Information
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