Rapid multi-temperature-zone fluorescent PCR (polymerase chain reaction) detector applied to micro-fluidic chip

Abstract

The utility model relates to a rapid multi-temperature-zone fluorescent PCR (Polymerase Chain Reaction) detector applied to a micro-fluidic chip. Comprising a bottom plate, a temperature control module, a chip set clamping box, a chip pressing mechanism, a chip set carrying mechanism, a temperature zone switching module, a heat dissipation module and a detection module. Aiming at simultaneous amplification of a plurality of micro-fluidic chips, a plurality of temperature control modules with fixed temperatures are arranged, and the chips can be moved to be switched back and forth among different temperature modules, so that rapid temperature circulation is realized, rapid reaction is maintained, temperature accuracy and uniformity under large-area heating are also maintained, and the amplification efficiency of the micro-fluidic chips is improved. Meanwhile, real-time fluorescent PCR detection of a plurality of micro-fluidic chips can be carried out.

Description

Technical Field

[0001] The utility model relates to the technical field of medical detection equipment, in particular to a rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip. Background Art

[0002] At present, the main method of in vitro amplification of nucleic acids is to mix the reagents and samples and place them in the same sample tube, and use the temperature control system to provide constant temperature or variable temperature control to achieve the amplification reaction. During PCR amplification, the speed of temperature increase and decrease depends mainly on the temperature increase and decrease speed of the temperature control system, which usually changes slowly. There are also some microfluidic chips that use fixed temperature zones to achieve temperature cycling by controlling the liquid to flow through different temperature zones at different times. This type of chip has relatively high requirements for liquid flow rate control and chip design. Also using fixed temperature zones are those that are adapted to 96-well plates, which achieve temperature cycling by moving the 96-well plate between different temperature zones.

[0003] At present, most technologies need to change the temperature of the temperature control module to reach the temperature required for amplification, and the temperature needs to be changed repeatedly, and at the same time, the temperature needs to be accurate, uniform, and the temperature ramp rate needs to be fast. For the design of the temperature control module, the technical difficulty is relatively large. The current common method is the Peltier technology, but although this technology has accurate temperature control, the temperature ramp rate is slow, which greatly limits the speed of PCR detection and cannot meet many occasions where test results need to be obtained quickly. For example, Chinese utility model patent CN221254584U discloses a dual-temperature zone PCR detection device based on a microfluidic chip, which improves detection efficiency by setting a high-temperature zone, a low-temperature zone, and a temperature control module, and entering the high and low temperature zone components through a motor controller. However, it was found in practice that the above technology can only achieve rapid temperature ramp control of a small area of ​​microfluidic chip area, but cannot achieve simultaneous reaction of multiple microfluidic chips at the same time. Utility Model Content

[0004] In order to solve the above problems, the utility model proposes a rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip.

[0005] The utility model provides a rapid multi-temperature zone fluorescence PCR detector for microfluidic chips, comprising a bottom plate, a temperature control module, a chipset cartridge, a chip pressing mechanism, a chipset mounting mechanism, a temperature zone switching module, a heat dissipation module, and a detection module; the temperature control modules are provided in plurality; a raised platform for heating the chip is provided on the top of the temperature control module, a heat sink is provided in the middle, and a heat dissipation fan is provided at the bottom; the chip pressing mechanism and the chipset mounting mechanism are provided on the front and back sides of the same fixed plate, wherein the chip pressing mechanism is provided with a plurality of chip compression springs at positions corresponding to the chips, the chip compression springs are fixed on the compression spring bottom plate, the compression spring bottom plate is fixedly connected to one side of a slide plate, the slide plate slides up and down along a guide rail, the guide rail is fixed to one side of the fixed plate, and the slide plate is on the other side. One side is connected to belt one, and belt one is driven by motor one. The chip pressing mechanism also includes a limiting optical coupler one fixed on the fixed plate, and an optical coupler baffle one is provided on the slide one. When the optical coupler baffle one enters the limiting optical coupler one and is triggered, it is 0 point; the chipset carrying mechanism includes a carrying plate, and two groups of limiting blocks are provided at the position where the chipset cartridge is placed on the carrying plate. The carrying plate is fixed on one side of slide two, and slide two slides up and down along guide rail two. The guide rail two is fixed on the other side of the fixed plate, and the other side of slide two is connected to belt two, and belt two is driven by motor two. The chipset carrying mechanism also includes a limiting optical coupler two fixed on the fixed plate, and an optical coupler baffle two is provided on the slide two. When the optical coupler baffle two enters the limiting optical coupler two and is triggered, it is 0 point.

[0006] Furthermore, the chipset card box includes a frame and side covers on both sides. The chip consisting of multiple chips is assembled at a fixed position in the chipset card box and is placed on the mounting board for use after the side covers are covered.

[0007] Furthermore, the temperature zone switching module is fixed to the base plate through a guide rail three, and the gear is driven to rotate by a motor three, which drives the belt to drive the screw to rotate. The screw drives the slider, and the fixed plate is fixed to the slider by screws. An optical coupler baffle three is provided on the slider, and a limited optical coupler three is provided on the base plate. When the optical coupler baffle three enters the limit optical coupler three and is triggered, it is 0 o'clock.

[0008] Furthermore, the heat dissipation module is a second heat dissipation fan, and the second heat dissipation fan is one or more, installed between multiple groups of temperature control modules and fixed on the support plate.

[0009] Furthermore, the detection module includes an excitation light source and a detection element, and the excitation light source includes a single-channel light source or a multi-channel light source.

[0010] Furthermore, the manner in which the motor 1 drives the slide 1 and the motor 2 drives the slide 2 includes belt transmission, screw transmission or gear transmission.

[0011] Furthermore, the raised platform is provided with a heat-conducting layer, and the material includes aluminum, copper, stainless steel or ceramic.

[0012] Furthermore, the heating source of the temperature control module is one or more of a semiconductor element, a resistance wire, an electric heating film, and a high-frequency electromagnetic.

[0013] The beneficial effects of the utility model are as follows:

[0014] The utility model is aimed at the simultaneous amplification of multiple microfluidic chips, and multiple fixed-temperature temperature control modules are set up. The chips can be moved back and forth between different temperature modules to achieve rapid temperature cycling. While maintaining rapid reaction, it also maintains temperature accuracy and uniformity under large-area heating, and can perform real-time fluorescence PCR detection on multiple microfluidic chips.

[0015] The microfluidic chip and the heating module of the utility model are detachable, and can be fast heated when heating is required, and can be quickly cooled when heating is not required.

[0016] The microfluidic chip of the utility model forms a flexible and detachable fitting structure with the temperature control module. The chip is first installed in the card box, limited for the first time, and then installed on the carrying mechanism. Then the chip is placed on the temperature control module. The clamping is then flexible (only the front, back, left and right positions are limited, and the upper and lower parts are attracted by magnetism and gravity to form flexibility and avoid hard fitting), which facilitates stable fitting with the temperature control module without damaging the chip.

[0017] The chipset carrying mechanism of the present invention is provided with a limiting structure that cooperates with the card box, adapts to the positioning between the card boxes, and ensures that the chip is positioned accurately.

[0018] The utility model fixes the chip pressing mechanism and the chipset loading mechanism to the front and back sides of the fixed plate, forming a dual Z-axis form on the same plate, saving space, and achieving the dual effects of chip loading and chip clamping and heating. It can also use transmission methods such as screw rods and gears instead of belt transmission methods.

[0019] This utility model can be configured with two or more temperature zones, allowing for rapid heating and cooling by separating and aligning the chips with the temperature zones as needed. Furthermore, each temperature control module is equipped with a heat sink and a cooling fan. If a single temperature control module needs to be cooled during different reactions, the cooling fan and heat sink can quickly bring that module to the desired temperature. Furthermore, a heat dissipation module is positioned between the multiple temperature control modules. The purpose of the heat dissipation module is to cool the chipset each time it switches from high to low temperature during the same reaction, accelerating the cooling process.

[0020] The utility model adopts multiple groups of compression springs to attach the chip to the temperature control module. The use of compression springs to compress the chip for heating can reduce the contact area between the compression device and the chip, ensuring the temperature stability of the chip. At the same time, because the compression spring slowly contacts the chip and slowly applies pressure, a certain form of flexible contact is formed, avoiding damage to the chip caused by hard contact.

[0021] The utility model has a rigorous structure, provides a new way to realize the possibility of biochip amplification detection, has multiple throughput, high integration, convenient operation, strong scalability, and can be used in conjunction with an automated system. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 , schematic diagram of the structure of a rapid multi-temperature zone fluorescence PCR instrument;

[0023] Figure 2 , schematic diagram of the temperature control module structure;

[0024] Figure 3 , schematic diagram of the chipset card box structure;

[0025] Figure 4 , schematic diagram of the chip pressing mechanism structure;

[0026] Figure 5 , schematic diagram of the chipset mounting mechanism structure;

[0027] Figure 6 , schematic diagram of the temperature zone switching module structure;

[0028] Figure 7 , Schematic diagram of the installation position of the heat dissipation module;

[0029] Figure 8 , schematic diagram of the structure of a rapid multi-temperature zone fluorescence PCR instrument from top view;

[0030] Figure 9 , side view of the structure of the rapid multi-temperature zone fluorescence PCR instrument;

[0031] Figure 10 , Schematic diagram of the rapid multi-temperature zone fluorescence PCR instrument with the door closed;

[0032] Figure 11 , Schematic diagram of the rapid multi-temperature zone fluorescence PCR instrument with the door open;

[0033] Figure 12 , Schematic diagram of the correspondence between the number of chips and the number of chip compression springs;

[0034] Figure 13 , Schematic diagram of the detection module using a multi-channel light source. DETAILED DESCRIPTION

[0035] The present invention will be further described below with reference to the following embodiments.

[0036] like Figure 1-5 As shown, a rapid multi-temperature zone fluorescent PCR detector for microfluidic chips includes a base plate 1, a temperature control module 2, a chipset cartridge 3, a chip pressing mechanism 4, a chipset carrying mechanism 5, a temperature zone switching module 6, a heat dissipation module 7, and a detection module 8; the temperature control module 2 is provided with two, a high-temperature temperature control module 25, and a low-temperature temperature control module 24; the top of the temperature control module 2 is provided with a raised platform 21 for heating the chip, the middle is provided with a heat sink 22, and the bottom is provided with a heat dissipation fan 23; the chip pressing mechanism 4 and the chipset carrying mechanism 5 are provided on the front and back sides of the same fixed plate 42, wherein the chip pressing mechanism 4 is provided with multiple groups of chip compression springs 41 at the position corresponding to the chip, the chip compression springs 41 are fixed on the compression spring base plate 49, the compression spring base plate 49 is fixedly connected to one side of a slide plate 44, the slide plate 44 slides up and down along a guide rail 43, the guide rail 43 is fixed to one side of the fixed plate 42, The other side of the slide 44 is connected to the belt 45, and the belt 45 is driven by the motor 46. The chip pressing mechanism 4 also includes a limiting optical coupler 47 fixed on the fixed plate 42, and an optical coupler baffle 48 is provided on the slide 44. When the optical coupler baffle 48 enters the limiting optical coupler 47 and is triggered, it is 0 o'clock; the chipset carrying mechanism 5 includes a carrying plate 59, and two groups of limiting blocks 51 are provided at the position where the chipset cartridge 3 is placed on the carrying plate 59. The carrying plate 59 is fixed on one side of the slide 2 54, and the slide 2 54 slides up and down along the guide rail 2 53. The guide rail 2 53 is fixed on the other side of the fixed plate 42, and the other side of the slide 2 54 is connected to the belt 2 55. The chipset carrying mechanism 5 also includes a limiting optical coupler 57 fixed on the fixed plate 42, and an optical coupler baffle 58 is provided on the slide 2 54. When the optical coupler baffle 58 enters the limiting optical coupler 57 and is triggered, it is 0 o'clock.

[0037] The chip clamping mechanism allows the chip to fit snugly against the temperature control module, ensuring that the temperature control module provides an accurate and stable temperature for the chip. The chipset mounting mechanism is used to position the chip cartridge and can move the chip up and down to control the distance between the chip and the temperature control module.

[0038] Specifically, the chipset cartridge 3 includes a frame 33 and side covers 32 on both sides. A chipset 31, consisting of multiple chips, is mounted in a fixed position within the chipset cartridge 3. After the side covers 32 are closed, the chipset cartridge is placed on the mounting plate 59 for use. The chipset cartridge carries a microfluidic chip and can carry one or more chips.

[0039] like Figure 6As shown, the temperature zone switching module 6 is fixed to the base plate 1 via a third guide rail 63. A third motor 66 drives a gear 62 to rotate, which in turn drives a belt 65 to rotate a screw 61. The screw 61 drives a slider 64. The fixing plate 42 is fixed to the slider 64 via screws. The slider 64 is provided with a third optical coupler baffle 68. The base plate 1 is provided with a third limited optical coupler 67. When the third optical coupler baffle 68 enters the third limited optical coupler 67, it is triggered, which is the zero point. The temperature zone switching module drives the chip clamping mechanism and the chipset loading mechanism to switch between different temperature control modules simultaneously.

[0040] like Figure 7 As shown, the heat dissipation module 7 is a second heat dissipation fan, which is one or more and is installed between multiple groups of temperature control modules 2 and fixed on the support plate 71. The heat dissipation module is used to cool the chip.

[0041] like Figure 8-9 As shown, the detection module 8 includes an excitation light source and a detection element. The excitation light source includes a single-channel light source or a multi-channel light source. The detection module is used to provide fluorescence detection after amplification.

[0042] Specifically, the manner in which the motor 1 drives the slide 1 and the motor 2 drives the slide 2 includes belt transmission, screw transmission or gear transmission.

[0043] Specifically, the raised platform 21 is provided with a heat-conducting layer, and the material includes aluminum, copper, stainless steel or ceramic.

[0044] The heating source of the temperature control module 2 is a semiconductor element. Specifically, the heating body of the temperature control module is a semiconductor heating plate or a resistance wire, an electric heating film, a high-frequency electromagnetic device, etc. that can achieve heating and temperature control.

[0045] When using, such as Figure 10-11 As shown, the rapid multi-temperature zone fluorescence PCR detector achieves fully automated detection through hardware and software control. Initially, the chip clamping mechanism 4 is raised to its highest position, with the chipset loading mechanism 5 at the bottom, near the instrument's door opening, making it easy for the operator to place the chipset cartridge 3. The instrument is turned on, and the loaded chipset cartridge 3 is placed onto the chipset loading mechanism 5. The reaction program is set, and the start test button is pressed. Following the program flow, the chip clamping mechanism 4 descends, and the chip compression spring 41 compresses the chip, ensuring that it is fully aligned with the raised platform 21 of the high-temperature temperature control module 25. The high-temperature and low-temperature temperature control modules 25 and 24 are heated to their respective set temperatures, and the reaction begins.

[0046] In the temperature cycle stage, the temperature zone switching module 6 drives the chip pressing mechanism 4 and the chipset loading mechanism 5 to carry the chipset cartridge 3 and move them to the top of the low temperature control module 24 to achieve different temperature cycles.

[0047] First, the chip reacts in the high-temperature temperature control module 25. When the temperature needs to be changed, the chip pressing mechanism 4 rises and completely clears the chip to an appropriate height (without colliding with the detection module). Then, the chipset loading mechanism 5 also rises and lifts the chipset cartridge 3, allowing the chip to completely clear the raised platform 21 of the high-temperature temperature control module 25 to an appropriate height.

[0048] The temperature zone switching module 6 drives the chip pressing mechanism 4 and the chipset loading mechanism 5 to move the chipset cartridge 3 together to above the low temperature control module 24;

[0049] The chipset mounting mechanism 5 descends to a position where the chipset on the chipset cartridge 3 is attached to the raised platform 21 on the low-temperature temperature control module 24; then the chip pressing mechanism 4 descends, and the chip compression spring 41 presses the chip so that the chip is completely fitted with the raised platform 21 of the low-temperature temperature control module 24. The chip obtains the temperature corresponding to the low-temperature temperature control module 24, completing a temperature switch.

[0050] Thus, the chipset cartridge 3 switches to different temperature zones for different periods of time according to the program setting to ensure that the amplification temperature conditions are quickly obtained;

[0051] If the chipset cartridge 3 moves from a high-temperature to a low-temperature zone, heat dissipation module 7 operates. When switching from a low-temperature to a high-temperature zone, heat dissipation module 7 ceases to operate. Furthermore, because temperature control module 2 and heat dissipation module 7 are independent of each other, temperature control module 2 remains operational. When switching from the low-temperature to the high-temperature zone of the chipset cartridge 3, although heat dissipation module 7 ceases to operate, cooling fan 1 23 within temperature control module 2 remains operational, maintaining the temperatures of each temperature control module.

[0052] A detection module 8 is installed above the temperature control module 2 corresponding to fluorescence collection. When collecting fluorescence, the detection module 8 is started to obtain the fluorescence data of the chip, such as Figure 9 shown.

[0053] like Figure 12 As shown, the number of chip compression springs 41 is determined according to the number of chips, and each chip corresponds to one chip compression spring 41 .

[0054] like Figure 13 As shown, the detection module 8 of the rapid multi-temperature zone fluorescence PCR detector applied to the microfluidic chip of the present invention can be a single-channel light source or a multi-channel light source.

[0055] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the present invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations that come within the meaning and range of equivalents of the claims be embraced within the present invention.

[0056] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. A rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip, characterized in that: The invention comprises a base plate (1), a temperature control module (2), a chipset card box (3), a chip pressing mechanism (4), a chipset mounting mechanism (5), a temperature zone switching module (6), a heat dissipation module (7), and a detection module (8); the temperature control module (2) is provided in plurality; a raised platform (21) for heating the chip is provided on the top of the temperature control module (2), a heat sink (22) is provided in the middle, and a heat dissipation fan (23) is provided at the bottom; the chip pressing mechanism (4) and the chipset mounting mechanism (5) are provided on the same fixed plate (42) on both sides, wherein the chip pressing mechanism (4) is provided with a plurality of chip compression springs (41) at positions corresponding to the chips, the chip compression springs (41) are fixed on a compression spring base plate (49), the compression spring base plate (49) is fixedly connected to one side of a slide plate (44), the slide plate (44) slides up and down along a guide rail (43), the guide rail (43) is fixed to one side of a fixed plate (42), the other side of the slide plate (44) is connected to a belt (45), and the belt (45) is driven by a motor (46) The chip pressing mechanism (4) further comprises a limiting optical coupler (47) fixed on the fixing plate (42), and an optical coupler baffle (48) is provided on the slide plate (44). When the optical coupler baffle (48) enters the limiting optical coupler (47) and is triggered, it is 0 o'clock; the chipset carrying mechanism (5) comprises a carrying plate (59), and two sets of limiting blocks (51) are provided at the position where the chipset cartridge (3) is placed on the carrying plate (59). The carrying plate (59) is fixed on one side of the slide plate (54). The slide plate (54) is provided with a plurality of limiting blocks (51). (54) slides up and down along the second guide rail (53), the second guide rail (53) is fixed on the other side of the fixed plate (42), the other side of the second slide plate (54) is connected to the second belt (55), and the second belt (55) is driven by the second motor (56), and the chipset mounting mechanism (5) also includes a second limiting optical coupler (57) fixed on the fixed plate (42), and an optical coupler baffle (58) is provided on the second slide plate (54), and when the optical coupler baffle (58) enters the second limiting optical coupler (57) and is triggered, it is 0 point.

2. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The chipset cartridge (3) comprises a frame (33) and side covers (32) on both sides. A chipset (31) consisting of a plurality of chips is installed at a fixed position in the chipset cartridge (3) and placed on the mounting plate (59) for use after the side covers (32) are closed.

3. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The temperature zone switching module (6) is fixed on the base plate (1) through the guide rail three (63), and the gear (62) is driven to rotate by the motor three (66), which drives the belt (65) to drive the screw rod (61) to rotate. The screw rod (61) drives the slider (64). The fixed plate (42) is fixedly mounted on the slider (64) by screws. The slider (64) is provided with an optical coupling baffle three (68). The base plate (1) is provided with a limited optical coupling three (67). When the optical coupling baffle three (68) enters the limited optical coupling three (67) and is triggered, it is 0 o'clock.

4. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The heat dissipation module (7) is a second heat dissipation fan. There are one or more second heat dissipation fans installed between multiple groups of temperature control modules (2) and fixed on the support plate (71).

5. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The detection module (8) comprises an excitation light source and a detection element, and the excitation light source comprises a single-channel light source or a multi-channel light source.

6. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The manner in which the motor 1 drives the slide 1 and the motor 2 drives the slide 2 includes belt transmission, screw transmission or gear transmission.

7. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The raised platform (21) is provided with a heat-conducting layer, and the material includes aluminum, copper, stainless steel or ceramic.

8. The rapid multi-temperature zone fluorescence PCR detector applied to a microfluidic chip according to claim 1, characterized in that: The heating source of the temperature control module (2) is one or more of a semiconductor element, a resistance wire, an electric heating film, and a high-frequency electromagnetic.

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