In vitro diagnostic analysis devices and reagent cartridges

Abstract

The present invention relates to an in vitro diagnostic analysis device and a reagent cartridge. When the rotary valve is rotated, the first chamber can be connected to any one of the second chambers, so that the reagents in the second chamber can be transferred to the first chamber and processed accordingly, thereby extracting the nucleic acid in the sample liquid. In addition, when the rotary valve is rotated, the first chamber can be connected to the PCR chamber, so that the first chamber can transfer the nucleic acid to the PCR chamber for amplification and detection. It can be seen that it can use highly integrated functional units to realize a multi-step biochemical reaction process, reduce manual operation, realize an automated solution for sample input and result output, reduce the reaction system and the required reagent dosage, greatly shorten the sample processing time, and the fully enclosed chip-reagent integrated system avoids cross contamination. Automatic control reduces the manual operation process and improves the consistency of operation.

Description

Technical Field

[0001] The present invention relates to the technical field of molecular diagnosis, and in particular to an in vitro diagnostic analysis device and a reagent cartridge. Background Art

[0002] Molecular diagnosis refers to the use of molecular biology methods to detect changes in the structure or expression levels of a patient's genetic material. Molecular diagnosis is a primary method for predictive diagnosis, applicable both to the diagnosis of individual genetic diseases and prenatal diagnosis. Molecular diagnosis primarily involves the detection of genes encoding disease-related structural proteins, enzymes, antigens, antibodies, and immunoreactive molecules. Key molecular diagnostic techniques include nucleic acid hybridization, polymerase chain reaction, and biochip technology.

[0003] However, nucleic acid testing of samples is generally divided into three steps: nucleic acid extraction, nucleic acid amplification, and nucleic acid detection. Currently, commercial nucleic acid testing products mostly perform nucleic acid extraction, nucleic acid amplification, and nucleic acid detection independently. After the completion of the previous step, the sample is moved to the subsequent equipment for completion. Consequently, the previous step cannot be effectively integrated with the subsequent step for continuous execution.

[0004] Traditional nucleic acid detection reagent products that complete each step independently require independent equipment to complete each step. Multiple devices are needed in a single nucleic acid detection process, and the equipment takes up a large amount of space. Furthermore, after the previous step is completed, the reagent sample needs to be moved to the subsequent equipment, which is cumbersome and time-consuming, and has high requirements on the environment and personnel. At the same time, for non-integrated reagent products, when switching from the previous step to the subsequent step, the reagent sample is also susceptible to contamination from the external environment or contamination of the detection environment during the movement process. Summary of the Invention

[0005] Based on this, it is necessary to overcome the defects of the existing technology and provide an in vitro diagnostic analysis device and reagent cartridge, which can realize a multi-step biochemical reaction process, thereby reducing manual operation, improving operation consistency, significantly shortening the processing time of reagent samples, avoiding cross contamination, and improving work efficiency.

[0006] The technical solution is as follows: A reagent cartridge, comprising: a microfluidic chip, wherein a first hole, a plurality of second holes, and a third hole are provided on a bottom surface of the microfluidic chip; the plurality of second holes and the third hole are circumferentially spaced apart around the first hole; the microfluidic chip is further provided with a plurality of first microfluidic channels arranged in a one-to-one correspondence with the plurality of second holes, and a PCR chamber connected to the third hole via the second microfluidic channel; a base, disposed on the bottom surface of the microfluidic chip, comprising a rotatable rotary valve; a connecting groove provided on the rotary valve, one end of the connecting groove corresponding to and connected to the first hole, and the other end of the connecting groove corresponding to one of all the second holes or the third hole as the rotary valve rotates; and a storage box, wherein the storage box is provided with a first chamber and a plurality of second chambers; the first chamber is connected to the first hole; the plurality of second chambers are in a one-to-one correspondence with and connected to the plurality of first microfluidic channels; the first chamber can be connected to a power source mechanism for promoting reagent flow, or all the second chambers and the PCR chamber can be connected to a power source mechanism for promoting reagent flow.

[0007] In one embodiment, the base also includes a fixed seat, and the rotary valve is rotatably arranged on the bottom surface of the fixed seat. A plurality of connecting holes are provided on the bottom surface of the fixed seat, and the first hole, all the second holes, and the third hole are respectively arranged in one-to-one correspondence with all the connecting holes and are connected.

[0008] In one embodiment, the base further includes a sealing gasket disposed between the fixing seat and the rotary valve; the sealing gasket is provided with a plurality of through holes; the plurality of through holes are disposed in a one-to-one correspondence with and connected to the plurality of communicating holes.

[0009] In one embodiment, a first recess is provided on the fixing seat, the rotary valve and the sealing gasket are both provided in the first recess and the rotary valve rotates relative to the fixing seat, the top surface of the sealing gasket is tightly fitted with the bottom wall of the first recess; a barb is provided on the wall of the first recess, and the barb is engaged and abutted against the rotary valve.

[0010] In one embodiment, the sealing gasket is fixedly arranged on the bottom wall of the first recess; a second recess is provided on the end surface of the rotary valve facing the sealing gasket, and the bottom of the sealing gasket is adapted to the second recess.

[0011] In one embodiment, the storage box is provided with a positioning post, the microfluidic chip is provided with a first positioning hole corresponding to the position of the positioning post, the fixing seat is provided with a second positioning hole corresponding to the position of the first positioning hole, and the positioning post is inserted into the first positioning hole and the second positioning hole.

[0012] In one embodiment, the reagent cartridge further includes a freeze-drying chamber for placing frozen reagents, and the second microfluidic channel is connected to the PCR chamber through the freeze-drying chamber.

[0013] In one embodiment, the microfluidic chip is further provided with a main flow channel, at least two branch flow channels and at least two first air vents; the main flow channel is connected to the freeze-drying chamber, one end of all the branch flow channels is connected to the main flow channel, and the other end of the branch flow channel is connected to the first air vent in a one-to-one correspondence; each of the branch flow channels is serially provided with the PCR chamber.

[0014] In one embodiment, the microfluidic chip is further provided with at least two first waterproof and breathable membranes, and the first waterproof and breathable membranes are provided on the hole walls of the first ventilation holes in a one-to-one correspondence.

[0015] In one embodiment, the storage box includes a first box body, a first cover plate covered on the first box body, and a sealing cover; the first chamber and multiple second chambers are all arranged on the first box body; the first cover plate is provided with a first loading hole and multiple second ventilation holes, the first loading hole is arranged corresponding to and connected with one of the second chamber positions, the sealing cover is detachably covered on the first loading hole, and the multiple second ventilation holes are arranged corresponding to and connected with the remaining second chamber positions.

[0016] In one embodiment, the storage box also includes a sealing membrane and a plurality of second waterproof and breathable membranes arranged on the top surface of the first cover plate; a second sample loading hole and a plurality of third ventilation holes are provided on the sealing membrane, the second sample loading hole corresponds to and is connected with the first sample loading hole, the plurality of third ventilation holes are arranged and are connected with the plurality of second ventilation holes in a one-to-one correspondence, and the plurality of second waterproof and breathable membranes are arranged on the hole walls of the plurality of third ventilation holes in a one-to-one correspondence.

[0017] In one embodiment, a first piston hole is provided on the first cover plate; the first piston hole is arranged corresponding to and communicated with the first chamber; the power source mechanism includes a piston head and a piston rod; the piston head is movably arranged in the first chamber; the piston head is connected to the piston rod; and the piston rod extends to the outside of the first chamber through the first piston hole.

[0018] An in vitro diagnostic analysis device includes the reagent cartridge described above, and further includes a temperature raising and lowering mechanism and a fluorescence detection mechanism. The temperature raising and lowering mechanism is arranged on one side of the microfluidic chip for raising or lowering the temperature of the PCR chamber, and the fluorescence detection mechanism is arranged on the other side of the microfluidic chip for optically detecting the PCR chamber.

[0019] When the above-mentioned reagent cartridge is working, reagents such as lysate, sample liquid, cleaning liquid and eluent are respectively installed in the interior of multiple second chambers. By driving the rotary valve to rotate, one end of the connecting groove is connected to the connecting hole corresponding to the first hole, and the other end of the connecting groove can be moved to a position connected to the remaining connecting holes as the rotary valve rotates. When the other end of the connecting groove is connected to one of the remaining connecting holes, the first chamber is connected through the first hole, the connecting groove, one of the second holes, the first microchannel corresponding to the second hole, and the second chamber corresponding to the first microchannel. Under the action of the power source mechanism, the reagent in one of the second chambers can be transferred to the first chamber for processing. Similarly, under the rotation of the rotary valve, the first chamber can also be connected to other second chambers. Under the action of the power source mechanism, the reagents in other second chambers can be transferred between the first chamber and processed accordingly, so that the nucleic acid in the sample liquid can be extracted. Furthermore, when the rotary valve rotates, it connects the first chamber via the first hole, the connecting groove, the third hole, the second microchannel corresponding to the third hole, and the PCR chamber corresponding to the second microchannel. Under the action of the power source mechanism, the first chamber can transfer nucleic acid to the PCR chamber for amplification and detection. Thus, it can utilize highly integrated functional units to implement multi-step biochemical reaction processes, reducing manual operations and achieving an automated sample-in-result-out solution. This reduces the reaction system and the required reagent volume, significantly shortening sample processing time. The fully enclosed chip-reagent integrated system avoids cross-contamination, and automated control reduces manual operations and improves operational consistency.

[0020] Since the above-mentioned in vitro diagnostic analysis device includes the above-mentioned reagent cartridge, the technical effect is brought by the reagent cartridge, and the beneficial effects are the same as those of the reagent cartridge, which will not be repeated here. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The drawings constituting a part of this application are used to provide a further understanding of the present invention. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0022] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0023] Figure 1 This is a schematic structural diagram of an in vitro diagnostic analysis device according to an embodiment of the present invention;

[0024] Figure 2 for Figure 1 The schematic diagram of the structure after the temperature rise and fall mechanism and the fluorescence detection mechanism are hidden;

[0025] Figure 3 for Figure 2 Schematic diagram of the decomposition structure;

[0026] Figure 4 for Figure 2 Schematic diagram of the cross-sectional structure;

[0027] Figure 5 for Figure 2 A perspective view from above;

[0028] Figure 6 This is a schematic diagram of the exploded structure of a base according to one embodiment of the present invention;

[0029] Figure 7 A bottom view of a fixing base according to an embodiment of the present invention;

[0030] Figure 8 A bottom view of a sealing gasket according to an embodiment of the present invention;

[0031] Figure 9 A top view of a rotary valve according to an embodiment of the present invention;

[0032] Figure 10 is a cross-sectional structural diagram of a base according to an embodiment of the present invention;

[0033] Figure 11 Schematic diagram of the structure of a microfluidic chip according to an embodiment of the present invention;

[0034] Figure 12 Schematic diagram of the bottom view of the microfluidic chip according to one embodiment of the present invention;

[0035] Figure 13 This is a schematic diagram of the exploded structure of a freeze-drying box according to one embodiment of the present invention;

[0036] Figure 14 This is a schematic diagram of the exploded structure of a storage box according to an embodiment of the present invention;

[0037] Figure 15 This is a schematic top view of the first box body according to an embodiment of the present invention.

[0038] 10. Reagent cartridge; 11. Base; 111. Fixing seat; 1111. Connecting hole; 1112. First recess; 1113. Barb; 1114. Positioning opening; 1115. Second positioning hole; 112. Rotary valve; 1121. Connecting groove; 1122. Second recess; 1123. Insertion hole; 113. Sealing pad; 1131. Through hole; 1132. Protrusion; 12. Microfluidic chip; 121. First recess; 1123. Insertion hole; 113. Sealing pad; 1131. Through hole; 1132. Protrusion; 12. Microfluidic chip; 121. First hole; 122, second hole; 123, third hole; 124, first microfluidic channel; 125, PCR chamber; 126, second microfluidic channel; 127, first positioning hole; 1283, main flow channel; 1284, branch flow channel; 1285, first vent hole; 1286, first waterproof breathable membrane; 13, storage box; 131, first chamber; 1311, first via hole; 132, second chamber; 1321, Second through hole; 132a, first reagent chamber; 132b, second reagent chamber; 132c, third reagent chamber; 132d, fourth reagent chamber; 132e, fifth reagent chamber; 132f, sixth reagent chamber; 133, positioning column; 134, first box body; 135, first cover plate; 1351, first piston hole; 1352, first sample addition hole; 1353, second vent hole; 136, blocking cover; 137, sealing membrane; 1371, second piston hole; 1372, second sample addition hole; 1373, third vent hole; 138, second waterproof and breathable membrane; 17, freeze-drying box; 171, second docking hole; 172, freeze-drying chamber; 173, third docking hole; 174, second box body; 175, second cover plate; 18, piston head; 19, piston rod; 20, temperature raising and lowering mechanism; 30, fluorescence detection mechanism; 40, driving rod. DETAILED DESCRIPTION

[0039] To make the above-mentioned objects, features, and advantages of the present invention more readily apparent, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings. The following description sets forth numerous specific details to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art may make similar modifications without departing from the scope of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0040] See Figures 1 to 3 , Figure 1 FIG1 shows a schematic structural diagram of an in vitro diagnostic analysis device according to an embodiment of the present invention. Figure 2 Shown Figure 1 The structural diagram after the temperature rise and fall mechanism 20 and the fluorescence detection mechanism 30 are hidden, Figure 3 Shown Figure 2Schematic diagram of an exploded structure. One embodiment of the present invention provides an in vitro diagnostic analysis device, comprising a reagent cartridge 10, a temperature control mechanism 20, and a fluorescence detection mechanism 30. The temperature control mechanism 20 is disposed on one side of a microfluidic chip 12 for increasing or decreasing the temperature of a PCR chamber 125. The fluorescence detection mechanism 30 is disposed on another side of the microfluidic chip 12 for optically detecting the PCR chamber 125.

[0041] See also Figures 4 to 10 , Figure 4 Shown Figure 2 Schematic diagram of the cross-sectional structure, Figure 5 Shown Figure 2 A perspective view from above, Figure 6 FIG. 1 is a schematic diagram of the exploded structure of the base 11 according to an embodiment of the present invention. Figures 7 and 8 The bottom views of the fixing seat 111 and the sealing gasket 113 according to an embodiment of the present invention are shown respectively. Figure 9 shows a top view of the rotary valve 112, Figure 10 FIG2 shows a cross-sectional structural diagram of a base 11 according to an embodiment of the present invention. Specifically, the reagent cartridge 10 includes a base 11 , a microfluidic chip 12 and a storage box 13 .

[0042] Also, see Figures 10 to 12 , Figure 11 FIG. 1 shows a schematic structural diagram of a microfluidic chip 12 according to an embodiment of the present invention. Figure 12 FIG. 1 is a bottom view schematic diagram of the microfluidic chip 12 according to an embodiment of the present invention.

[0043] The bottom surface of the microfluidic chip 12 is provided with a first hole 121, multiple second holes 122, and a third hole 123. The multiple second holes 122 and the third holes 123 are spaced circumferentially around the first hole 121. The microfluidic chip 12 is also provided with multiple first microchannels 124, which correspond one-to-one with the multiple second holes 122. The microfluidic chip 12 is also provided with a PCR chamber 125, and the third hole 123 is connected to the PCR chamber 125 via a second microchannel 126.

[0044] See also Figure 3 、 Figure 4 and Figure 6The base 11 is provided on the bottom surface of the microfluidic chip 12. Specifically, the base 11 includes a fixed base 111 and a rotary valve 112 rotatably provided on the bottom surface of the fixed base 111. The bottom surface of the fixed base 111 is provided with a plurality of connecting holes 1111. The plurality of connecting holes 1111 are connected to the plurality of connecting holes in a one-to-one correspondence. The rotary valve 112 is provided with a connecting groove 1121. One end of the connecting groove 1121 is connected to the connecting hole 1111 corresponding to the first hole 121. The other end of the connecting groove 1121 can move to a position connected to the remaining connecting holes 1111 as the rotary valve 112 rotates.

[0045] It is understandable that, as an optional solution, the fixed seat 111 may not be set, that is, the rotary valve 112 may be rotatably set on the base 11 and located on the bottom surface of the microfluidic chip 12, one end of the connecting groove 1121 corresponds to and is connected to the first hole 121, and the other end of the connecting groove 1121 corresponds to and is connected to one of all the second holes 122 or the third hole 123 as the rotary valve 112 rotates.

[0046] See also Figure 3 、 Figure 4 and Figure 6 The storage box 13 is disposed on the top surface of the microfluidic chip 12. The storage box 13 is provided with a first chamber 131 and a plurality of second chambers 132. A first via 1311 is provided on the bottom wall of the first chamber 131, and the first via 1311 is connected to the first hole 121. The plurality of second chambers 132 correspond to and are connected to the plurality of first microchannels 124. Specifically, a second via 1321 is provided on the bottom wall of the second chamber 132, and the plurality of second vias 1321 correspond to and are connected to the plurality of first microchannels 124.

[0047] Furthermore, the first chamber 131 can be connected to a power source mechanism for driving the flow of reagents; alternatively, all of the second chambers 132 and the PCR chamber 125 can be connected to a power source mechanism for driving the flow of reagents. In this embodiment, the power source mechanism includes, but is not limited to, a piston drive mechanism, an air pump drive mechanism, etc., as long as it can provide a driving force to allow the reagents to flow from the first chamber 131 into the second chamber 132 and the PCR chamber 125, and from the second chamber 132 into the first chamber 131.

[0048] It should be noted that first hole 121 is a through hole because it needs to connect the first through hole and the first via hole 1311. Furthermore, second hole 122, third hole 123, and fourth hole can all be blind holes or through holes, without limitation. Furthermore, first via hole 1311 and second via hole 1321 are both through holes, meaning that first chamber 131 connects to first hole 121 via first via hole 1311, and second chamber 132 connects to the fourth hole via second via hole 1321.

[0049] When the reagent cartridge 10 is working, reagents such as lysate, sample solution, cleaning solution and eluent are respectively installed in the interior of the plurality of second chambers 132, and the rotary valve 112 is driven to rotate, so that one end of the communicating groove 1121 is connected to the communicating hole 1111 corresponding to the first hole 121, and the other end of the communicating groove 1121 can be moved to a position connected to the remaining communicating holes 1111 as the rotary valve 112 rotates. When the other end of the communicating groove 1121 is connected to one of the remaining communicating holes 1111, the first chamber 131 is connected through the first hole 121, the communicating hole 1111 corresponding to the first hole 121, the communicating groove 1121, and the other end of the communicating groove 1121. The connecting hole 1111, the second hole 122, the first microchannel 124 corresponding to the second hole 122, and one of the second chambers 132 corresponding to the first microchannel 124 are connected. Under the action of the power source mechanism, the reagent in one of the second chambers 132 can be transferred to the first chamber 131 for processing. Similarly, under the rotation of the rotary valve 112, the first chamber 131 can also be connected with other second chambers 132. Under the action of the power source mechanism, the reagents in other second chambers 132 can be transferred to the first chamber 131 and processed accordingly, so that the nucleic acid in the sample liquid can be extracted. Furthermore, when the rotary valve 112 rotates, it can also connect the first chamber 131 through the first hole 121, the connecting hole 1111 corresponding to the first hole 121, the connecting groove 1121, the connecting hole 1111 corresponding to the other end of the connecting groove 1121, the third hole 123, the second microchannel 126 corresponding to the third hole 123, and the PCR chamber 125 corresponding to the second microchannel 126. Under the action of the power source mechanism, the first chamber 131 can transfer the nucleic acid to the PCR chamber 125 for amplification and detection. Thus, it can utilize highly integrated functional units to implement multi-step biochemical reaction processes, reduce manual operations, and realize an automated sample-in-result-out solution, reducing the reaction system and the required reagent volume, significantly shortening sample processing time, and the fully enclosed chip-reagent integrated system avoids cross-contamination. Automated control reduces manual operations and improves operational consistency.

[0050] See also Figures 6 to 10In one embodiment, the base 11 further comprises a sealing gasket 113 arranged between the fixed seat 111 and the rotary valve 112. The sealing gasket 113 is provided with a plurality of through holes 1131. The plurality of through holes 1131 are arranged in a one-to-one correspondence with the plurality of communicating holes 1111 and are in communication. In this way, by arranging the sealing gasket 113 between the rotary valve 112 and the fixed seat 111, the sealing gasket 113 can ensure good sealing performance at the docking position between one end of the communicating groove 1121 and the communicating hole 1111 corresponding to the first hole 121, and ensure the sealing performance at the docking position between the other end of the communicating groove 1121 and the remaining communicating holes 1111. In addition, in order to ensure sealing performance, the top surface of the sealing gasket 113 is in close contact with the bottom surface of the fixed seat 111, and the bottom surface of the sealing gasket 113 is in close contact with the top surface of the rotary valve 112. This can avoid the presence of a gap between the top surface of the sealing gasket 113 and the bottom surface of the fixed seat 111, which would cause the reagent to flow into any other communicating hole 1111 through the gap. In addition, the sealing gasket 113 is specifically an elastic gasket, such as a silicone gasket, a rubber gasket, a latex gasket, etc. Of course, it can also be an elastic gasket made of other elastic materials, which is not limited here.

[0051] See also Figure 10 In one embodiment, a first recess 1112 is provided on the bottom surface of the fixed seat 111. The rotary valve 112 and the sealing gasket 113 are both disposed within the first recess 1112, and the rotary valve 112 rotates relative to the fixed seat 111. Specifically, the sidewalls of the rotary valve 112 can rotate relative to the sidewalls of the first recess 1112. The top surface of the sealing gasket 113 is tightly fitted against the bottom wall of the first recess 1112. Barbs 1113 are provided on the walls of the first recess 1112, and the barbs 1113 engage and contact the rotary valve 112. Thus, the sealing gasket 113 and the rotary valve 112 are mounted within the first recess 1112, and the barbs 1113 contact the bottom surface of the rotary valve 112, thereby restricting the position of the rotary valve 112. This ensures that the two side surfaces of the sealing gasket 113 are in close contact with the rotary valve 112 and the fixed seat 111, respectively. Furthermore, the rotary valve 112 operates more stably during rotation. Specifically, to improve stability, the number of barbs 1113 is not limited to one, and can be, for example, two, three, or another number, that is, two or more barbs 1113 are used to synchronously contact the bottom surface of the rotary valve 112. The barbs 1113 can be, for example, elastic hooks, such as metal hooks, silicone hooks, rubber hooks, plastic hooks, etc., and can be an integrated structure with the fixing seat 111, or a separate structure assembled together. There is no limitation here, and the configuration can be based on actual needs. In addition, to facilitate the free rotation of the rotary valve 112 within the first recess 1112, the rotary valve 112 is cylindrical, and the first recess 1112 is adapted to the shape of the rotary valve 112.

[0052] As an optional solution, a slot can also be provided on the wall of the first recess 1112, and the outer edge of the rotary valve 112 can be rotatably provided in the slot. On the one hand, the two side surfaces of the sealing gasket 113 can be in close contact and cooperation with the rotary valve 112 and the fixed seat 111 respectively, and on the other hand, the rotation of the rotary valve 112 can also be achieved.

[0053] See also Figure 10 In one embodiment, the sealing gasket 113 is fixedly mounted on the bottom wall of the first recess 1112. A second recess 1122 is provided on the end surface of the rotary valve 112 facing the sealing gasket 113. The bottom of the sealing gasket 113 is adapted to fit within the second recess 1122, and both the bottom surface of the sealing gasket 113 and the bottom wall of the second recess 1122 are circular. In this manner, the rotary valve 112 can freely rotate relative to the sealing gasket 113, and the rotary valve 112 and the sealing gasket 113 are accurately aligned. Thus, when the rotary valve 112 is rotated by a predetermined angle, the other end of the connecting groove 1121 can be accurately moved to a position where it communicates with one of the plurality of through-holes 1131.

[0054] See also Figure 1 and Figure 10 Furthermore, to facilitate the rotation of the rotary valve 112, the rotary valve 112 is connected to the drive rod 40, and the rotary valve 112 is driven to rotate by the drive rod 40. For example, a socket 1123 for assembling with the drive rod 40 is provided on the end surface of the rotary valve 112 facing away from the sealing gasket 113. The shape of the socket 1123 is adapted to the shape of the end of the drive rod 40. In this way, by inserting the end of the drive rod 40 into the socket 1123 and rotating the drive rod 40, the rotary valve 112 can be rotated accordingly, thereby adjusting the angle. Of course, the drive rod 40 can also use other methods to drive the rotary valve 112 to rotate, which is not limited here.

[0055] See Figure 7 and Figure 8 It should be noted that, in order to ensure that the sealing gasket 113 is fixedly arranged on the bottom wall of the first recess 1112, as an example, a protrusion 1132 is provided on the outer edge of the sealing gasket 113, and a limiting opening 1114 adapted to the protrusion 1132 is provided on the bottom wall of the first recess 1112. The protrusion 1132 is arranged in the limiting opening 1114, so that the sealing gasket 113 can be fixedly arranged on the bottom wall of the first recess 1112, that is, when the rotary valve 112 rotates, the sealing gasket 113 will not rotate with the rotary valve 112.

[0056] In one embodiment, the microfluidic chip 12 is glued, welded, or fixed on the top surface of the fixing seat 111 through a mounting member; the storage box 13 is glued, welded, or fixed on the top surface of the microfluidic chip 12 through a mounting member.

[0057] In one embodiment, a positioning post 133 is provided on the bottom surface of the storage box 13. A first positioning hole 127 corresponding to the position of the positioning post 133 is provided on the microfluidic chip 12, and a second positioning hole 1115 corresponding to the position of the first positioning hole 127 is provided on the fixing seat 111. The positioning post 133 is inserted into the first positioning hole 127 and the second positioning hole 1115. In this way, after the positioning post 133 is inserted into the first positioning hole 127 and the second positioning hole 1115, the fixing seat 111, the microfluidic chip 12 and the storage box 13 can be accurately aligned, which is conducive to rapid assembly and high assembly efficiency. Specifically, the number of positioning posts 133 can be, for example, one, two, three or more, and the number of the first positioning hole 127 and the second positioning hole 1115 can be, for example, one, two, three or more.

[0058] See Figure 3 、 Figure 5 、 Figure 12 and Figure 13 In one embodiment, the reagent cartridge 10 further includes a freeze-drying chamber 172 for placing frozen reagents. The second microfluidic channel 126 is communicated with the PCR chamber 125 through the freeze-drying chamber 172. Specifically, the reagent cartridge 10 further includes a freeze-drying box 17 for placing frozen reagents. The freeze-drying box 17 is provided with a freeze-drying chamber 172. In addition, specifically, the freeze-drying box 17 is provided with a second docking hole 171 communicated with the second microfluidic channel 126, a freeze-drying chamber 172 communicated with the second docking hole 171, and a third docking hole 173 communicated with the freeze-drying chamber 172. The third docking hole 173 is communicated with the PCR chamber 125. In this way, the freeze-dried reagent can be set inside the freeze-drying chamber 172, and after the nucleic acid is extracted from the first chamber 131, the rotary valve 112 is rotated to make the first chamber 131 communicate with the first hole 121, the connecting hole 1111 corresponding to the first hole 121, the connecting groove 1121, the connecting hole 1111 corresponding to the other end of the connecting groove 1121, the third hole 123, the second microchannel 126 corresponding to the third hole 123, and the PCR chamber 125 corresponding to the second microchannel 126. For example, the piston pushes the first chamber 131 to make the second microchannel 126 communicate with the PCR chamber 125. The nucleic acid in a chamber 131 enters the freeze-drying chamber 172 through the first through-hole 1311, the first hole 121, the connecting hole 1111 corresponding to the first hole 121, the connecting groove 1121, the connecting hole 1111 corresponding to the other end of the connecting groove 1121, the third hole 123, the second microfluidic channel 126 corresponding to the third hole 123, and the second docking hole 171. After the nucleic acid dissolves the freeze-drying reagent in the freeze-drying chamber 172, it continues to move forward under the pushing pressure of the first chamber 131 and enters the PCT chamber for amplification and optical detection.

[0059] See Figure 3 、 Figure 5 、 Figure 12 and Figure 13 In one embodiment, the microfluidic chip 12 is further provided with a main channel 1283, at least two branch channels 1284 and at least two first vents 1285. The main channel 1283 is connected to the freeze-drying chamber 172, one end of all the branch channels 1284 is connected to the main channel 1283, and the other end of the branch channel 1284 is connected to the first vent 1285 in a one-to-one correspondence. A PCR chamber 125 is provided in series on each branch channel 1284. In this way, the nucleic acid and the freeze-dried reagent enter the interior of the PCR chamber 125 in each branch channel 1284 respectively through the main channel 1283. By performing amplification and optical detection simultaneously in more than two PCR chambers 125, the work efficiency can be greatly improved, and the reliability of the test results can be improved. Furthermore, since the first vent 1285 can exhaust air outward, it can maintain air pressure balance, allowing the nucleic acid and lyophilized reagent to enter the interior of the PCR chamber 125 in the branch channel 1284 under the pressure of the air. In addition, each PCR chamber 125 can specifically encapsulate different reaction reagents, for example, to achieve multiple nucleic acid detection. It should be noted that the specific number of PCR chambers 125, such as 2, 3, 4, 8, 16, etc., is set according to actual needs and is not limited here.

[0060] See Figure 5 and Figure 11 In one embodiment, the microfluidic chip 12 is further provided with at least two first waterproof breathable membranes 1286, which are disposed one-to-one on the walls of the at least two first vent holes 1285. Thus, the first waterproof breathable membranes 1286 allow gas to escape, maintaining pressure balance within the branch channel 1284, while preventing liquid from escaping and external liquid from entering, thereby preventing contamination of the reagents within the PCR chamber 125.

[0061] See also Figure 14 In one embodiment, the storage box 13 includes a first box body 134, a first cover plate 135 covering the first box body 134, and a blocking cover 136. The first chamber 131 and the plurality of second chambers 132 are both provided on the first box body 134. The first cover plate 135 is provided with a first piston hole 1351, a first sample loading hole 1352 and a plurality of second ventilation holes 1353. The first piston hole 1351 is arranged in correspondence with and communicated with the first chamber 131, the first sample loading hole 1352 is arranged in correspondence with and communicated with one of the second chambers 132, the blocking cover 136 is detachably covered on the first sample loading hole 1352, and the plurality of second ventilation holes 1353 are arranged in correspondence with and communicated with the remaining second chambers 132.

[0062] See also Figure 14Furthermore, the storage box 13 also includes a sealing membrane 137 and a plurality of second waterproof and breathable membranes 138 disposed on the top surface of the first cover plate 135. The sealing membrane 137 is provided with a second piston hole 1371, a second sample loading hole 1372, and a plurality of third vent holes 1373. The second piston hole 1371 corresponds to and is connected to the first piston hole 1351, the second sample loading hole 1372 corresponds to and is connected to the first sample loading hole 1352, the plurality of third vent holes 1373 are disposed in a one-to-one correspondence with and are connected to the plurality of second vent holes 1353, and the plurality of second waterproof and breathable membranes 138 are disposed in a one-to-one correspondence on the walls of the plurality of third vent holes 1373.

[0063] See also Figure 14 , an embodiment of the above-mentioned power source mechanism includes a piston head 18 and a piston rod 19. The piston head 18 is movably arranged in the first chamber 131, and the piston head 18 is connected to the piston rod 19. The piston rod 19 extends to the outside of the first chamber 131 through the first piston hole 1351. In this way, when the first chamber 131 is connected to one of the second chambers 132 by rotating to the specified position, the piston head 18 is driven to move by the piston rod 19. During the movement of the piston head 18, a pushing force or a suction force can be provided. When a pushing force is provided, the reagent in the first chamber 131 can be pushed into one of the second chambers 132. When a suction force is provided, the reagent in one of the second chambers 132 can be sucked into the interior of the first chamber 131.

[0064] It should be noted that the specific number and specific volume size of the plurality of second chambers 132 are set according to actual conditions and are not limited here.

[0065] As an optional solution, the piston head 18 and the piston rod 19 are not set in the first chamber 131, but instead the piston head 18 and the piston rod 19 are set in multiple second chambers 132, that is, the piston head 18 in the second chamber 132 is used to provide power to achieve transfer between the first chamber 131; similarly, a suction mechanism is set at the end of the branch channel 1284, and power is provided according to the actual working state to move the nucleic acid in the first chamber 131 to the PCR chamber 125 in the branch channel 1284.

[0066] As an optional solution, the piston head 18 and the piston rod 19 are not provided in the first chamber 131 , but the pushing force and the suction force are provided by connecting the first chamber 131 to a device with inflation and suction functions.

[0067] To make this embodiment clearer, the specific methods of nucleic acid extraction, amplification, and optical detection are described in detail below. The nucleic acid extraction steps are as follows:

[0068] Step S10: Provide Figures 1 to 3 The reagent cartridge 10 shown;

[0069] Specifically, see Figure 4 、 Figure 14 and Figure 15 , the specific number of the second chamber 132 is 6, and according to Figure 4 From left to right, the chambers shown are named as the first reagent chamber 132a, the second reagent chamber 132b, the third reagent chamber 132c, the fourth reagent chamber 132d, the fifth reagent chamber 132e and the sixth reagent chamber 132f respectively; the first reagent chamber 132a is used to load the magnetic bead lysis solution, for example, 1000ul; the second reagent chamber 132b is in an empty state and is used to inject the sample to be tested; the third reagent chamber 132c is used to load the first cleaning solution, for example, 500ul; the fourth reagent chamber 132d is used to load the second cleaning solution, for example, 500ul; the fifth reagent chamber 132e is in an empty state; and the sixth reagent chamber 132f is used to load the eluent, for example, 80ul. When there are six second chambers 132, correspondingly, there are six second vias 1321, six first microfluidic channels 124, and six second holes 122. When the rotary valve 112 is rotated, the first chamber 131 can be connected via the first hole 121, the connecting hole 1111 corresponding to the first hole 121, the connecting groove 1121, the connecting hole 1111 corresponding to the other end of the connecting groove 1121, the second hole 122, the first microfluidic channel 124 corresponding to the second hole 122, and one of the second chambers 132 corresponding to the first microfluidic channel 124. In other words, by rotating the rotary valve 112, the first chamber 131 can be connected to the first reagent chamber 132a, the second reagent chamber 132b, the third reagent chamber 132c, the fourth reagent chamber 132d, the fifth reagent chamber 132e, and the sixth reagent chamber 132f, respectively. In addition, there are specifically eight PCR chambers 125 , and different reaction reagents are encapsulated in the eight PCR chambers 125 to achieve multiple nucleic acid detection.

[0070] Step S20: Open the blocking cover 136, inject, for example, 1000 μl of the sample liquid to be tested into the second reagent chamber 132 b, and seal the sample injection port with the blocking cover 136;

[0071] Step S30: Rotate the rotary valve 112 to a designated position so that the second reagent chamber 132b is connected to the first chamber 131, and pull the piston rod 19 to draw the sample liquid in the second reagent chamber 132b into the first chamber 131; then rotate the rotary valve 112 to a designated position so that the first reagent chamber 132a is connected to the first chamber 131, and pull the piston rod 19 to draw the lysate in the first reagent chamber 132a into the first chamber 131; continue to rotate the rotary valve 112 to a designated position so that the fifth reagent chamber 132e is connected to the first chamber 131, and push the piston rod 19 to push the mixed liquid of the sample liquid and the lysate into the fifth reagent chamber 132e. Repeatedly push and pull the piston rod 19, for example 3 to 4 times, to fully mix the sample liquid and the lysate, so that the analyte in the sample liquid is fully lysed, releasing the nucleic acid, and the magnetic beads in the lysate adsorb the nucleic acid to the surface of the magnetic beads through chemical bonding. At this time, move the external magnet to the side wall of the fifth reagent chamber 132e to adsorb the magnetic beads to the side wall of the fifth reagent chamber 132e; pull the piston rod 19 to draw the waste liquid without magnetic beads in the fifth reagent chamber 132e into the first chamber 131, then rotate the rotary valve 112 to connect the second chamber 132 with the fifth reagent chamber 132e, and push the piston rod 19 to push the waste liquid into the second reagent chamber 132b. At this time, the nucleic acid lysis process is completed; the external magnet is removed, and the rotary valve 112 is rotated to the specified position so that the first chamber 131 is connected to the third reagent chamber 132c, and the piston rod 19 is pulled to draw the first cleaning liquid in the third reagent chamber 132c into the first chamber 131. The rotary valve 112 is continued to be rotated to the specified position so that the first chamber 131 is connected to the fifth reagent chamber 132e, and the piston rod 19 is pushed to push the first cleaning liquid into the fifth reagent chamber 132e. The piston rod 19 is repeatedly pushed and pulled, for example 3 to 4 times, to fully mix the first cleaning liquid with the magnetic beads in the fifth reagent chamber 132e, and to wash away impurities such as cell walls and proteins remaining on the surface of the magnetic beads. Repeat the steps of removing the sample lysate mixture, pushing the first cleaning solution containing impurities back into the third reagent chamber 132c, completing the first cleaning of the nucleic acids. Similar to the first cleaning step for nucleic acids, by rotating the rotary valve 112 in different positions, the second cleaning solution in the fourth reagent chamber 132d can be used to complete the second cleaning of the nucleic acids. At this time, the magnetic beads adsorbed with nucleic acids remain in the fifth reagent chamber 132e, and the second cleaning solution containing impurities is pushed back into the fourth reagent chamber 132d. Similar to the first cleaning step for nucleic acids described above, by rotating the rotary valve 112 in different positions, the nucleic acids are eluted from the surface of the magnetic beads using the eluent in the sixth reagent chamber 132f. The eluent is mixed with the eluent, and the nucleic acid-containing eluent is pumped into the first chamber 131. Simultaneously, the magnetic beads are adsorbed to the sidewalls of the fifth reagent chamber 132e.

[0072] In addition, the steps of nucleic acid amplification and optical detection are as follows:

[0073] Step S40: Turn the rotary valve 112 to a designated position to connect the first chamber 131 with the freeze-drying chamber 172, push the eluent containing nucleic acid into the freeze-drying chamber 172 of the freeze-drying cartridge 17 to dissolve the freeze-dried powder in the freeze-drying cartridge 17, and then pump the eluent back into the first chamber 131. Repeat this process, for example, 3 to 4 times, until the freeze-dried powder is completely redissolved.

[0074] Step S50: After the lyophilized powder is completely redissolved in the eluent containing nucleic acid, the piston rod 19 is pushed to allow the eluent to fill the interior of the eight PCR chambers 125. The PCR chambers 125 are subjected to thermal cycling treatment by the temperature raising and lowering mechanism 20, and the samples in the PCR chambers 125 are subjected to fluorescence detection by the optical detection mechanism, thereby completing PCR amplification and detection.

[0075] The technical features of the above embodiments can be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0076] The above embodiments merely illustrate several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make various modifications and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

[0077] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like to indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0078] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0079] In the present invention, unless otherwise specified or limited, the terms "installed," "connected," "connect," "fixed," etc. should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection, electrical connection; direct connection, or indirect connection through an intermediate medium; internal communication between two components, or interaction between two components, unless otherwise specified. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0080] In the present invention, unless otherwise expressly specified or limited, when a first feature is "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediary. Furthermore, when a first feature is "above," "above," or "above" a second feature, it may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. When a first feature is "below," "below," or "below" a second feature, it may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0081] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it may be directly on the other element or there may be an intermediate element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be an intermediate element. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used herein are for illustrative purposes only and do not represent the only implementation methods.

Claims

1. A reagent cartridge, characterized in that: The reagent cartridge comprises: A microfluidic chip, wherein a first hole, a plurality of second holes, and a third hole are provided on a bottom surface of the microfluidic chip; the plurality of second holes and the third holes are circumferentially spaced apart around the first hole; the microfluidic chip is further provided with a plurality of first microfluidic channels arranged in a one-to-one correspondence with the plurality of second holes, and a PCR chamber connected to the third hole via the second microfluidic channel; The base is arranged on the bottom surface of the microfluidic chip, and the base includes a fixed base and a rotary valve rotatably arranged on the bottom surface of the fixed base; a connecting groove is provided on the rotary valve, one end of the connecting groove corresponds to and is connected with the first hole, and the other end of the connecting groove is connected with one of all the second holes or the third hole as the rotary valve rotates; a plurality of connecting holes are provided on the bottom surface of the fixed base, and the first hole, all the second holes, and the third hole are respectively arranged in a one-to-one correspondence with all the connecting holes and are connected; the base also includes a sealing gasket arranged between the fixed base and the rotary valve; a sealing gasket is provided on the sealing gasket There are multiple through holes; the multiple through holes are arranged in a one-to-one correspondence with the multiple communicating holes and are connected; a first recess is provided on the fixing seat, the rotary valve and the sealing gasket are both arranged in the first recess and the rotary valve rotates relative to the fixing seat, and the top surface of the sealing gasket is tightly fitted with the bottom wall of the first recess; a barb is provided on the wall of the first recess, and the barb is engaged and abuts against the rotary valve; the bottom surface of the sealing gasket is in close contact with the top surface of the rotary valve; a protrusion is provided on the outer edge of the sealing gasket, and a limiting opening adapted to the protrusion is provided on the bottom wall of the first recess, and the protrusion is provided in the limiting opening; A storage box, wherein the storage box is provided with a first chamber and a plurality of second chambers; the first chamber is connected to the first hole; the plurality of second chambers correspond to and are connected to the plurality of first microfluidic channels one by one; the first chamber can be connected to a power source mechanism for promoting the flow of reagents, or all of the second chambers and the PCR chambers can be connected to a power source mechanism for promoting the flow of reagents.

2. The reagent cartridge according to claim 1, wherein The sealing gasket is an elastic gasket.

3. The reagent cartridge according to claim 1, wherein There are at least two barbs, and the two or more barbs synchronously abut against the bottom surface of the rotary valve.

4. The reagent cartridge according to claim 1, wherein The barb is an elastic hook body.

5. The reagent cartridge according to claim 1, wherein The sealing gasket is fixedly arranged on the bottom wall of the first recess; a second recess is provided on the end surface of the rotary valve facing the sealing gasket, and the bottom of the sealing gasket is adapted to the second recess.

6. The reagent cartridge according to claim 1, wherein The storage box is provided with a positioning post, the microfluidic chip is provided with a first positioning hole corresponding to the position of the positioning post, the fixing seat is provided with a second positioning hole corresponding to the position of the first positioning hole, and the positioning post is inserted into the first positioning hole and the second positioning hole.

7. The reagent cartridge according to claim 1, wherein The reagent cartridge further includes a freeze-drying chamber for placing frozen reagents, and the second microfluidic channel is connected to the PCR chamber through the freeze-drying chamber.

8. The reagent cartridge according to claim 7, wherein: The microfluidic chip is also provided with a main flow channel, at least two branch flow channels and at least two first ventilation holes; the main flow channel is connected to the freeze-drying chamber, one end of all the branch flow channels is connected to the main flow channel, and the other end of the branch flow channel is connected to the first ventilation hole in a one-to-one correspondence; each of the branch flow channels is serially provided with the PCR chamber.

9. The reagent cartridge according to claim 8, wherein At least two first waterproof and breathable membranes are also provided on the microfluidic chip, and the first waterproof and breathable membranes are provided on the hole walls of the first ventilation holes in a one-to-one correspondence.

10. The reagent cartridge according to claim 1, wherein The storage box includes a first box body, a first cover plate covered on the first box body, and a blocking cover; the first chamber and multiple second chambers are all arranged on the first box body; the first cover plate is provided with a first sample loading hole and multiple second ventilation holes, the first sample loading hole is arranged corresponding to and connected with one of the second chamber positions, the blocking cover is detachably covered on the first sample loading hole, and the multiple second ventilation holes are arranged corresponding to and connected with the remaining second chamber positions.

11. The reagent cartridge according to claim 10, wherein: The storage box also includes a sealing film and multiple second waterproof and breathable membranes arranged on the top surface of the first cover plate; the sealing film is provided with a second sample loading hole and multiple third ventilation holes, the second sample loading hole corresponds to and is connected with the first sample loading hole, the multiple third ventilation holes are arranged and connected with the multiple second ventilation holes in a one-to-one correspondence, and the multiple second waterproof and breathable membranes are arranged on the hole walls of the multiple third ventilation holes in a one-to-one correspondence.

12. The reagent cartridge according to claim 10, wherein: A first piston hole is provided on the first cover plate; the first piston hole is arranged corresponding to and communicated with the first chamber; the power source mechanism includes a piston head and a piston rod; the piston head is movably arranged in the first chamber; the piston head is connected to the piston rod; and the piston rod extends to the outside of the first chamber through the first piston hole.

13. An in vitro diagnostic analysis device, characterized in that: The in vitro diagnostic analysis device includes a reagent cartridge as described in any one of claims 1 to 12, and further includes a temperature raising and lowering mechanism and a fluorescence detection mechanism. The temperature raising and lowering mechanism is arranged on one side of the microfluidic chip for performing temperature raising or temperature lowering treatment on the PCR chamber, and the fluorescence detection mechanism is arranged on the other side of the microfluidic chip for performing optical detection on the PCR chamber.

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