Multichannel microfluidic sample delivery unit

Abstract

This paper provides a multi-channel microfluidic sampling device, which includes a body; a sample loading port; multiple capillary sampling channels spaced apart inside the body, with the first end of each capillary sampling channel communicating with the sample loading port; and multiple puncture tubes spaced apart on the first side of the body, each puncture tube communicating with the second end of one of the multiple capillary sampling channels. The second end of each puncture tube extending outside the body is a pointed tip. The inner diameter of the puncture tube, or the inner diameter at the contact point between the puncture tube and the capillary sampling channel, is larger than the inner diameter of the capillary sampling channel, preventing liquid samples from continuing to enter the puncture tubes through capillary action. The multi-channel microfluidic sampling device is provided with a snap-fit ​​opening, and the side wall of the snap-fit ​​opening has first and second snap-fit ​​positions. A detection card is installed at the second snap-fit ​​position. This multi-channel microfluidic sampling device is suitable for simultaneously dispensing samples from multiple sampling ports on a detection card. It is simple to operate, avoids cross-contamination, and easily automates the dispensing of micro-detection cards.

Description

[0001] Priority application This application claims priority to Chinese application CN2020114314743, filed on December 10, 2020, which is incorporated herein by reference in its entirety.

[0002] Divisional application This application is a divisional application of Chinese invention patent application filed on September 7, 2021 [Application No.: 2021800788732] [Title: Multichannel microfluidic sample loading device, components and applications thereof]. Technical Field

[0003] This application relates to a sample dispensing device for a test card, and more particularly to a multi-channel microfluidic sample dispensing device suitable for simultaneously dispensing samples from multiple dispensing ports on a test card, and a sample dispensing assembly having the same device. This application also relates to the application of the test card sample dispensing device and assembly. Background Technology

[0004] Various testing cards (such as blood typing cards) often use soft film materials (such as aluminum foil or plastic film) to seal the filler (such as various reagents and / or gel microspheres) inside. Before use, this sealing film needs to be torn or punctured to add the sample. For example, traditional blood typing cards require punching holes before use, which can easily cause cross-contamination; for blood typing cards containing multiple microspheres, each card requires multiple sample additions, which is cumbersome and makes it difficult to ensure accurate and equal sample addition. Furthermore, with the miniaturization of various reagent cards, the inner diameter of the sample dispensing port on the reagent card is only 1-2 mm or less, making manual sample addition difficult.

[0005] Therefore, some researchers have designed and improved the sample dispensing operation for reagent cards. For example, utility model patent CN204359800U discloses a blood type reagent card puncture device, including: multiple spikes and a barcode scanner mounted on a frame, and a robotic arm used in conjunction with the spikes. The barcode scanner is located on the side of the spikes. One end of each spike is fixed to the frame, and the other end has a spike pointing in the same direction. The spikes are arranged in several rows, with a different number of spikes in each row, and the spikes in the same row are evenly spaced. Although this technical solution can achieve the purpose of puncturing and dispensing samples, its overall manufacturing cost is high, the operation is complex, and cross-contamination is still a problem.

[0006] For example, utility model patent CN210142129U discloses a puncture device for microcolumn gel blood typing cards, comprising: a spike for puncturing, a mounting base for setting the spike, and a handheld part for holding the puncture device; the handheld part includes two sides arranged parallel to each other along the length of the mounting base, and the two sides are located on the same side of the mounting base as the spike and perpendicular to the mounting base; the internal distance between the two sides is equal to the width of the microcolumn gel card. By using multiple puncture devices, different detection tubes (microcolumns) can be punctured by different spikes, avoiding cross-contamination when the same spike punctures different detection tubes. However, in use, it can only puncture and cannot perform quantitative sample separation.

[0007] For quantitative sample dispensing, some researchers have proposed new microfluidic chips. For example, Chinese patent application CN111604098A discloses two types of sample dispensing microfluidic chips. The first type has a sample dispensing orifice on the surface of the chip body, and the second type has a sample dispensing orifice on the side of the chip body. Both types have a dispensing channel, a quantitative channel, a flow control valve, a reaction channel, and a waste liquid chamber inside the chip body. The dispensing channel is used to deliver the sample to each quantitative channel and the waste liquid chamber; the quantitative channel is connected to the downstream reaction channel through the flow control valve; the reaction channel is used for the detection reaction and can be pre-filled with reaction reagents or have the sample to be tested delivered to the reaction chamber; the waste liquid chamber is used to hold excess sample. In other words, both microfluidic chips achieve quantitative sample dispensing through capillary dispensing channels connected to the sample dispensing orifices. However, these two sample dispensing methods still have problems such as cross-contamination and high detection costs. Summary of the Invention

[0008] The purpose of this invention is to provide a multi-channel microfluidic sampling device and its sampling components, so as to partially solve or alleviate the above-mentioned deficiencies in the prior art. It can sample multiple channels of the test card, is simple to operate, avoids cross-contamination, and facilitates the automation of sampling and detection.

[0009] To solve the aforementioned technical problems, the present invention specifically adopts the following technical solution: A first aspect of the present invention is to provide a multi-channel microfluidic sample loading device, comprising: ontology; A sample loading port for receiving liquid samples, wherein the sample loading port (or opening) of the sample loading port is located on the first surface (e.g., the upper surface) of the body. Multiple capillary sampling channels are spaced apart inside the main body. The first end of each capillary sampling channel communicates with the sample loading hole. When the liquid sample is added to the sample loading hole, the liquid sample fills the multiple capillary sampling channels through capillary action. Multiple puncture tubes are spaced apart on the first side of the main body and extend into the interior of the main body. The first ends of the multiple puncture tubes located inside the main body are respectively connected to the second ends of the multiple capillary sampling channels. The second ends of the multiple puncture tubes located outside the main body are pointed tips for puncture. The inner diameter of the puncture tube or the inner diameter of the puncture tube at the contact point with the capillary sampling channel is larger than the inner diameter of the capillary sampling channel, so that the liquid sample will not continue to enter the puncture tube through capillary action.

[0010] In some embodiments of the present invention, the body is sheet-like or plate-like, and the plurality of capillary sampling channels are spaced apart inside the body along the length direction of the body.

[0011] In some embodiments of the present invention, the second end of the capillary sampling channel is connected to the first end of the puncture tube through a connecting channel, the connecting channel being perpendicular to the plane in which the plurality of capillary sampling channels are located.

[0012] In some embodiments of the present invention, the connecting channel is a capillary channel.

[0013] In some embodiments of the present invention, the multi-channel microfluidic sampling device further includes: two snap-fit ​​openings formed by sidewalls extending from both sides of the body for insertion into a detection card; when the detection card is pushed into the snap-fit ​​openings, the pointed ends of the plurality of puncture tubes puncture the sealing membrane covered by the opening ends of the plurality of micropillars on the detection card.

[0014] In some embodiments, the sidewall is provided with a limiting protrusion that can cooperate with the limiting slot on the detection card; or, the sidewall is provided with a limiting slot that can cooperate with the limiting protrusion on the detection card.

[0015] In some embodiments of the present invention, the body is further provided with a waste liquid tank communicating with the sample loading hole. When there is too much liquid sample in the sample loading hole or under the action of centrifugal force, the liquid sample in the sample loading hole can flow into the waste liquid tank.

[0016] In some embodiments of the present invention, a baffle is provided in the waste liquid tank to restrict the liquid sample from flowing back to the sample loading hole.

[0017] In some embodiments of the present invention, the inner diameter of the capillary sampling channel is 0.5 mm, and the inner diameter of the connecting channel is 0.8 mm.

[0018] In some embodiments of the present invention, the inner diameter of the capillary sampling channel or the connecting channel is 0.5 mm-1.2 mm.

[0019] In some embodiments of the present invention, the baffle is a sheet-like structure protruding from the bottom of the waste liquid tank, and the height of the baffle is lower than the height of the waste liquid tank; when the liquid sample overflows the top of the sheet-like structure due to excessive liquid sample during the sample loading process, the overflowing liquid sample enters the waste liquid tank.

[0020] In some embodiments of the present invention, the baffle is hydrophobically treated.

[0021] In some embodiments of the present invention, a hydrophobic layer is provided on the baffle.

[0022] In some embodiments of the present invention, the sample loading hole has a conical structure.

[0023] In some embodiments of the present invention, the first ends of the plurality of capillary channels are distributed circumferentially along the sample loading orifice. Preferably, they are symmetrically distributed circumferentially.

[0024] In some embodiments of the present invention, the capillary channels are covered with a hydrophilic membrane layer.

[0025] A second aspect of the present invention is to provide a multi-channel microfluidic sampling assembly, which includes any of the above-mentioned multi-channel microfluidic sampling devices and a detection card, wherein the multi-channel microfluidic sampling device is provided with a snap-fit ​​opening that can be inserted into the detection card, and a first snap-fit ​​position and a second snap-fit ​​position are provided at intervals along the extension direction of the sidewall of the snap-fit ​​opening. The detection card is mounted at the second card-connecting position in a manner that allows it to move relative to the card-connecting opening; When the detection card is moved from the second snap-fit ​​position to the first snap-fit ​​position under the action of an external force, the tips of the multiple puncture tubes on the multi-channel microfluidic sampling device pierce the sealing membrane covered by the opening ends of the multiple microcolumns on the detection card.

[0026] In some embodiments of the present invention, a limiting card protrusion is provided on one or both sides of the detection card. Correspondingly, the card opening includes a guide rail for providing a moving path for the detection card, and the guide rail is provided with a first limiting card groove and a second limiting card groove that can cooperate with the limiting card protrusion at the first card position and the second card position, respectively. When the limiting card protrusion engages with the second limiting card groove, the detection card engages with the card engagement opening at the second engagement position. When the limiting card protrusion disengages from the second limiting card slot under the action of an external force, the detection card can move along the guide rail toward the puncture tube; and when the limiting card protrusion moves to the first limiting card slot under the action of an external force and cooperates with the first limiting card slot, the detection card engages with the engagement opening at the first engagement position.

[0027] In some embodiments of the present invention, a limiting protrusion is provided on one or both sides of the detection card. Correspondingly, the locking opening includes a guide rail for providing a moving path for the detection card, and the guide rail is provided with a first limiting slot corresponding to the first locking position, which can cooperate with the limiting protrusion. The end of the limiting protrusion is fixedly connected to the guide rail at the second locking position, and the connection between the limiting protrusion and the second locking position is provided with a breakable break line (i.e., in the initial state, the limiting protrusion is fixedly connected to the second locking position on the guide rail). When the limiting card protrusion is disconnected from the guide rail under the action of an external force, the detection card can move along the guide rail toward the puncture tube; and when the limiting card protrusion moves to the first limiting card groove under the action of an external force and cooperates with the first limiting card groove, the detection card and the carding opening are engaged at the first carding position.

[0028] A third aspect of the present invention is to provide another multi-channel microfluidic sampling assembly, which includes any of the above-mentioned multi-channel microfluidic sampling devices and a detection card, wherein the multi-channel microfluidic sampling device is provided with a snap-fit ​​opening that can be inserted into the detection card, and the detection card is provided with a second snap-fit ​​position and a first snap-fit ​​position at intervals on one or both sides along a direction that gradually moves away from the micropillar. The detection card is mounted at the second card-connecting position in a manner that allows it to move relative to the card-connecting opening; When the detection card is moved from the second snap-fit ​​position to the first snap-fit ​​position under the action of an external force, the multiple puncture tubes on the multi-channel microfluidic sampling device puncture the sealing membrane covering the opening ends of the multiple microcolumns on the detection card.

[0029] In some embodiments of the present invention, a first limiting slot and a second limiting slot are respectively provided on one or both sides of the detection card at the first and second locking positions; correspondingly, the locking opening includes a sliding guide rail for providing a sliding path for the detection card, and the sliding guide rail is provided with a limiting protrusion that can cooperate with the first limiting slot and the second limiting slot; When the limiting card protrusion engages with the second limiting card groove, the detection card engages with the card engagement opening at the second engagement position; When an external force causes the limiting card protrusion to disengage from the second limiting card groove, the detection card can move along the guide rail toward the puncture tube; and when an external force causes the first limiting card groove to move to the position of the limiting card protrusion and cooperate with the limiting card protrusion, the detection card engages with the engagement opening at the first engagement position.

[0030] In some embodiments of the present invention, the snap-fit ​​opening includes: a guide rail for providing a moving path for the detection card, and a limiting snap-fit ​​protrusion is provided on the guide rail; correspondingly, one or both sides of the detection card are provided with a first limiting snap-fit ​​groove that can cooperate with the limiting snap-fit ​​protrusion at the first snap-fit ​​position; wherein, the end of the limiting snap-fit ​​protrusion is fixedly connected to the second snap-fit ​​position on the detection card, and a breakable break line is provided at the connection between the limiting snap-fit ​​protrusion and the second snap-fit ​​position (i.e., in the initial state, the limiting snap-fit ​​protrusion is fixedly connected to the detection card at the second snap-fit ​​position); When an external force causes the limiting card protrusion to disconnect from the detection card, the detection card can move along the guide rail toward the puncture tube; and when an external force causes the first limiting card groove to move to the position of the limiting card protrusion and cooperate with the limiting card protrusion, the detection card and the locking opening are locked at the first locking position.

[0031] A fourth aspect of the present invention is to provide the application of the above-mentioned multi-channel microfluidic sampling device or multi-channel microfluidic sampling assembly in the sampling of blood typing cards.

[0032] Beneficial effects: The multi-channel microfluidic sampling device provided in this invention application ingeniously combines capillary action and centrifugal force to achieve multi-channel sampling of the test card. It is simple to operate, avoids cross-contamination, and facilitates the automation of sampling and testing. Furthermore, compared to existing technologies that use side sampling, requiring adjustments or improvements to the transport equipment, centrifuges, and other subsequent operating equipment to ensure the microfluidic chip remains vertical during transportation and testing, thus increasing manufacturing and testing costs, the multi-channel microfluidic sampling device provided by this invention eliminates the need for adjustments or improvements to existing equipment during sampling, transportation, and subsequent testing. This significantly reduces manufacturing and testing costs, meaning that the multi-channel microfluidic sampling device provided by this invention has a wider range of applications and better versatility.

[0033] The multi-channel microfluidic sample dispensing component provided by this invention, by setting first and second snap-fit ​​positions on the sample dispensing device, or by setting first and second snap-fit ​​positions on the detection card, allows the detection card and the sample dispensing device to be directly snapped into the second snap-fit ​​position (i.e., the detection card and the sample dispensing device are integrated into one unit). In this case, because a certain safe distance is maintained between the tip of the puncture tube on the sample dispensing device and the microcolumn on the detection card, it is suitable for scenarios where sample dispensing and quantitative separation are not required, such as during carrying or transportation. In this scenario, the one-to-one correspondence between the puncture tube on the sampling device and the microcolumn on the test card is ensured, while also guaranteeing the airtightness of the microcolumn on the test card. When sample addition and quantitative dispensing are required, the test card can be moved to engage with the sampling device at the first engagement position. At this point, the tip of the puncture tube on the sampling device pierces the sealing membrane. Since each puncture tube on the sampling device corresponds to one microcolumn (i.e., a one-to-one correspondence between puncture tube and microcolumn), quantitative dispensing is achieved while preventing cross-contamination. The multi-channel microfluidic sampling structure provided by this invention is simple and easy to carry or transport. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0035] Figure 1 This is a three-dimensional structural diagram of the multi-channel microfluidic sample loading device of the present invention, showing a portion of the structure on its upper surface; Figure 2 This is a three-dimensional structural schematic diagram of the multi-channel microfluidic sample loading device of the present invention, showing the internal structure near its lower surface; Figure 3 This is a schematic diagram of the multi-channel microfluidic sample loading device of the present invention, showing the internal structure near its lower surface; Figure 4 This shows the state of the multi-channel microfluidic sampling device of the present invention before it is connected to the detection card; Figure 5 This shows the state of the multi-channel microfluidic sampling device of the present invention after it is connected to the detection card; Figure 6 A three-dimensional structural diagram of a detection card used in conjunction with the multi-channel microfluidic sampling device of the present invention; Figure 7This is a schematic diagram of the structure of a multi-channel microfluidic sampling assembly in its initial state, as an exemplary embodiment of the present invention.

[0036] In the figure, 1. Body; 2. Sample loading port; 3. Capillary sample channel; 4. Connecting channel; 5. Puncture tube; 6. Tip end; 7. Waste liquid tank; 8. Snap-fit ​​opening; 9. Limiting clip protrusion; 10. Baffle; 11. Detection card; 12. Limiting clip groove (first limiting clip groove 12a, second limiting clip groove 12b); 13. Microcolumn; 14. Side wall. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0038] In this document, suffixes such as "module," "part," or "unit" used to denote elements are used only for the purpose of illustrative purposes and have no specific meaning in themselves. Therefore, "module," "part," or "unit" may be used interchangeably.

[0039] In this document, the terms "upper," "lower," "inner," "outer," "front," "rear," "one end," and "the other end," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the present invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0040] In this document, unless otherwise explicitly specified and limited, the terms "installed," "equipped with," "connected," etc., should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium; it can be a connection within two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0041] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0042] In this article, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0043] Since the multi-channel microfluidic sampling device provided in this paper involves centrifugation during use, for ease of description, the end that is relatively far from the centrifuge axis during centrifugation is called the distal end, and the end that is relatively close to the centrifuge axis is called the proximal end.

[0044] In this paper, the surface on one side of the sample loading port (or sample loading port) of the multichannel microfluidic sample loading device is referred to as the upper surface (or the first surface), and the other side is referred to as the lower surface (or the second surface).

[0045] Unless otherwise stated, when referring to a structure as being "inside" a multichannel microfluidic sample dispenser, it means that the structure is surrounded by the body material or other materials of the multichannel microfluidic sample dispenser and is not in direct contact with the external space.

[0046] In this document, for the purpose of distinction, "sample loading" is usually used to describe the process of the multi-channel microfluidic sample loading device of the present invention receiving samples, while "sample addition" is used to describe the process of the detection card receiving samples.

[0047] Example 1: Reference Figures 1-5 In an exemplary embodiment of the present invention, the body 1 of the multi-channel microfluidic sampling device is generally plate-shaped or block-shaped, that is, its dimensions in the length L and width W directions are much larger than its dimensions in the thickness (or height) H direction. For example, the length L and width W are both several centimeters, while the thickness H is only a few millimeters.

[0048] In an exemplary embodiment of the present invention, the multi-channel microfluidic sample loading device has a sample loading port 2 with an opening (i.e., a sample loading port) located on the upper surface (or first surface) of the body 1. Multiple (i.e., two or more) capillary sample loading channels 3 are spaced apart inside the body 1 along the plane direction (i.e., the plane containing the length and width dimensions, or the horizontal direction). The first end of each capillary sample loading channel 3 communicates with the sample loading port 2, and the other end (i.e., the second end) is evenly spaced at the distal end of the body 1. Multiple connecting channels 4 are provided inside the body 1 generally along the thickness direction (i.e., perpendicular to the plane containing the capillary sample loading channels 3), each communicating with the other end (i.e., the second end) of each capillary sample loading channel 3. Multiple puncture tubes 5 are evenly spaced at the distal side of the body 1 (i.e., the first side near the second end of the capillary sample loading channel 3), extending into the body 1. The first end of each puncture tube 5 located inside the body 1 communicates with the connecting channel 4, and the other end (i.e., the second end extending to the outside of the body 1) is a pointed tip 6 for puncture. Thus, the other end (i.e., the second end) of the capillary sampling channel 3 is connected to the first end of the puncture tube 5 located inside the body 1 via the connecting channel 4. The capillary sampling channel 3 is a capillary channel, meaning its inner diameter is suitable for the flow of liquid samples through capillary action, typically less than 1.5 mm, for example, 0.5-1.2 mm or smaller.

[0049] In some embodiments, the aforementioned connecting channel 4 can be a capillary channel, in which case it can be considered an extension of the capillary sampling channel 3; of course, the connecting channel 4 can also be a non-capillary channel, in which case it can serve as a flow stop. It should be understood that the connecting channel 4 and its arrangement along the thickness direction are also beneficial for processing, facilitating communication between the capillary sampling channel 3 and the inner cavity of the puncture tube 5.

[0050] Figures 2-5 This can be considered a cross-sectional view with part of the lower surface (the area where the capillary sampling channel 3 is located) removed to show the internal structure of the multi-channel microfluidic sample dispensing device of the present invention. Furthermore, for ease of processing (especially the capillary sampling channel 3) and / or hydrophilic treatment, it is also possible to first process it into the structure shown in the figure, and then cover the lower surface layer (such as a hydrophilic membrane) by means of gluing or bonding, achieving the same effect as having these capillary sampling channels 3 and other structures located inside the body 1. Therefore, this multi-channel microfluidic sample dispensing device, whether integrally injection molded, prepared by a layered processing method, or a main structure prepared by a layered processing method but excluding the lower surface layer, should all be covered within the scope of protection of this application.

[0051] In some embodiments, further, in order to accommodate excessive sample added to the sample loading hole 2, a waste liquid tank 7 may be provided inside the body 1 near the sample loading hole 2 (in the distal direction). Furthermore, in order to prevent the sample from entering the waste liquid tank 7 when the sample is not excessive and to prevent the sample in the waste liquid tank 7 from returning to the sample loading hole 2, thereby causing cross-contamination, a baffle 10 may be provided in the waste liquid tank 7 near the sample loading hole 2.

[0052] In some embodiments, the baffle 10 serves as a raised plate at the bottom of the waste liquid tank 7, and can only enter the waste liquid tank 7 when the sample overflows its top due to excessive sample volume.

[0053] In addition, to facilitate sample entry into the waste liquid tank 7, the waste liquid tank 7 may have an opening on the upper surface of the body 1. When the body 1 is made of a hydrophilic material, the baffle 10 may be treated to have hydrophobic properties, for example, by adding a hydrophobic layer, to further prevent the sample entering the waste liquid tank 7 from returning to the sample loading hole 2.

[0054] In some embodiments, for convenient use with the detection card 11, a snap-fit ​​opening 8 is provided at the distal end of the body 1, and limiting snap protrusions 9 are respectively provided on the two opposite sidewalls 14 of the snap-fit ​​opening 8. When the detection card 11 is pushed into the snap-fit ​​opening 8, its two sides abut against the two opposite sidewalls 14 of the snap-fit ​​opening 8 and are positioned by the limiting snap protrusions 9.

[0055] The detection card 11 used in conjunction with the multi-channel microfluidic sampling device of an exemplary embodiment of the present invention has multiple microcolumns 13 (or detection columns), see [link to relevant documentation]. Figure 6The open ends of these micropillars 13 correspond to the tip 6 of the puncture tube 5. When the detection card 11 is pushed into the snap-fit ​​opening 8, the tip 6 of each puncture tube 5 can pierce the thin film material covering the open end of each micropillar 13. The detection card 11 has at least one set of limiting slots 12 on both sides corresponding to the limiting protrusion 9. For example, when the detection card 11 is provided with two sets of limiting slots 12, one set of limiting slots 12 (i.e., the first limiting slot at the first snap-fit ​​position on the detection card) cooperates with the limiting protrusion 9, so that the tip 6 of the puncture tube 5 is in the state of piercing the thin film material. The other set of limiting slots 12 (i.e., the second limiting slot at the second snap-fit ​​position on the detection card) can be slightly higher. When they cooperate with the limiting protrusion 9, they only serve to attach the detection card 11 to the multi-channel microfluidic sample application device of the present invention. At this time, the tip 6 of the puncture tube 5 does not pierce the thin film material on the detection card 11.

[0056] See Figure 4 and Figure 5 In use, insert the detection card 11 into the card slot 8 and push it upwards so that the tip 6 of each puncture tube 5 pierces the covering film material on each micropillar 13. Then, add a liquid sample (such as blood) into the upward sample well 2. Under capillary action, the sample enters each capillary sample channel 3.

[0057] When the connecting channel 4 is a capillary channel, the liquid sample also enters the connecting channel 4; when the connecting channel 4 is a non-capillary channel, the liquid sample only fills each capillary sampling channel 3. The inner diameter of the puncture tube 5, or the inner diameter of the part that contacts the connecting channel 4, can usually be set large enough so that even when the connecting channel 4 is a capillary channel, the liquid sample will not continue to enter it through capillary action.

[0058] After sample loading, the multi-channel microfluidic sample loading device of the present invention, equipped with the detection card 11, is placed into the centrifuge slot of a centrifuge for centrifugation. Under centrifugal force, the remaining sample in the loading orifice 2 will quickly flow into the waste liquid tank 7; the sample in the capillary sampling channel 3 and the connecting channel 4 (when they are capillary channels) will enter the microcolumns 13 of the detection card 11 through the puncture tube 5, thus loading the detection card 11. Due to the presence of the baffle 10, the sample that enters the waste liquid tank 7 after centrifugation cannot return to the loading orifice 2.

[0059] The usage process is described here in chronological order. Those skilled in the art will understand that it is not necessary to operate in this order. For example, the multi-channel microfluidic sample loading device of the present invention can be placed in a centrifuge and then the detection card can be inserted and the sample loaded in sequence, or the sample can be loaded and the detection card can be inserted in sequence.

[0060] Obviously, the sample loading volume of each microcolumn 13 can be ensured to be the same or different by adjusting the length and / or inner diameter of each capillary sampling channel 3 and connecting channel 4 (when it is a capillary channel).

[0061] In some embodiments, the sample loading orifice 2 adopts a tapered structure that is larger at the top and smaller at the bottom. The larger sample loading orifice facilitates sample alignment, while the smaller bottom makes it easier for the sample to contact the capillary sample channel 3, thus speeding up the sample loading process compared to existing sample loading methods.

[0062] Furthermore, in some embodiments, see Figure 4 and Figure 5 Since the first ends of multiple capillary sampling channels 3 are distributed circumferentially (e.g., symmetrically) along the sample loading hole 2 and are directly connected to the bottom of the sample loading hole 2, the sample can enter each capillary sampling channel 3 almost simultaneously during sample addition, thereby further accelerating the sample separation speed. Compared with the prior art, where the sample needs to enter the quantitative channel sequentially according to the arrangement order of the component channels along the length of the body, this greatly increases the sample separation efficiency and detection efficiency.

[0063] Understandably, when the slot on the centrifuge is suitable for simultaneously fixing the multi-channel microfluidic sampling device and the detection card of the present invention, the multi-channel microfluidic sampling device of the present invention may not include the snap-fit ​​opening 8, because when both are fixed on the centrifuge at the same time, the puncture operation can be completed on the centrifuge.

[0064] Understandably, the number of capillary sampling channels 3 in the multi-channel microfluidic sampling device of the present invention can be dozens or more. When used in conjunction with a detection card having the same number of microcolumns, it is suitable for large-scale micro-sampling and enables simultaneous detection of multiple items.

[0065] The multi-channel microfluidic sampling device of the exemplary embodiment of the present invention is particularly suitable for sampling gel microcolumn blood typing cards. Since gel microcolumn blood typing cards require centrifugation to detect cell agglutination reactions during blood typing, by using the multi-channel microfluidic sampling device of the exemplary embodiment of the present invention, centrifugation can be continued after sampling, allowing the entire process of sample loading, separation, addition, and detection to be easily achieved on a centrifuge, making it suitable for automated operation.

[0066] The following is an example of a multi-channel microfluidic sampling device of the present invention, prepared for dispensing samples onto a miniature blood typing card with six microcolumns: The main body of the multi-channel microfluidic sampling device of the present invention is made of polycarbonate (PC) material, with a thickness of approximately 4.5 mm. A hydrophilic membrane layer is adhered to cover the capillary sampling channels and other structures to facilitate the flow of aqueous liquids such as blood. The sample loading orifice has a conical structure with an opening diameter of 5 mm and a bottom diameter of 3 mm. The bottom surface of the waste liquid tank is rectangular, with dimensions of 6 mm x 2 mm. The baffle inside the waste liquid tank has dimensions of 2 mm x 0.5 mm and a thickness of 0.5 mm. Six capillary sampling channels are provided, each with an inner diameter of 0.5 mm and a length of 1.8 cm. The six connecting channels are also capillary channels, each with an inner diameter of 0.8 mm and a length of 1.5 mm. Other structures and dimensions can be set with reference to the description above.

[0067] Example 2 Based on the multi-channel microfluidic sampling device in Embodiment 1 above, the present invention also provides a multi-channel microfluidic sampling assembly, which includes: the multi-channel microfluidic sampling device in Embodiment 1 above, and a detection card; the difference is that, see [link to previous section]. Figure 7 In some embodiments, the multi-channel microfluidic sampling device has a first snap-fit ​​position and a second snap-fit ​​position spaced apart on the sidewall of the snap-fit ​​opening, extending along the sidewall (i.e., extending along the distal end, or gradually approaching the detection card). The detection card 11 is installed at the second snap-fit ​​position in a way that it can move relative to the snap-fit ​​opening 8. At this time, the detection card 11 is only installed on the multi-channel microfluidic sampling device, and the tip 6 of the puncture tube 5 on the multi-channel microfluidic sampling device does not pierce the sealing film covered by the microcolumn opening end on the detection card 11. When the detection card 11 is moved from the second snap-fit ​​position to the first snap-fit ​​position under the action of an external force, the multiple puncture tubes on the multi-channel microfluidic sampling device puncture the sealing membrane covered by the opening ends of the multiple micropillars 13 on the detection card 11.

[0068] In some embodiments, when the component is shipped (or in its initial state), the detection card 11 is installed at the second snap-fit ​​position of the snap-fit ​​opening on the multi-channel microfluidic sample dispenser. For example, it is fixedly connected to the second snap-fit ​​position by a limiting snap 9 provided on the detection card 11, and the connection is provided with a break line that is easy to break. In this state, there is a certain distance e between the tip of the puncture tube and the film on the micropillar, and this distance is slightly less than or equal to the interval between the first snap-fit ​​position and the second snap-fit ​​position, that is, the puncture tube has not yet pierced the film on the micropillar of the detection card. When the connection is broken along the break line, and the detection card is moved from the second snap-fit ​​position to the first snap-fit ​​position (for example, the limiting snap 9 engages with the limiting slot), the tip of the puncture tube can pierce the film on the micropillar.

[0069] In other embodiments, the detection card and the sample application device are independent of each other when the component is manufactured. However, after the first assembly, the detection card 11 is snapped onto the multi-channel microfluidic sample application device (specifically, it is snapped onto the second snapping position of the snapping opening 8 by the snap-fit ​​between the limiting card protrusion 9 and the limiting card groove). Similarly, at this time, there is a certain distance e between the tip of the puncture tube and the film on the microcolumn, and this distance is slightly less than or equal to the interval between the first snapping position and the second snapping position. When the detection card is moved from the second snapping position to the first snapping position under the action of an external force (for example, the limiting card protrusion and the limiting card groove snap-fit), the tip of the puncture tube can pierce the film on the microcolumn.

[0070] See Figure 7 In some specific embodiments, a limiting card protrusion 9 is provided on each of the two sides (or one side) of the detection card. Correspondingly, the card-connecting opening 8 includes: a guide rail for providing a moving path for the detection card (specifically, the guide rail can be two side walls 14 extending from both sides of the main body, or the guide rail is provided on the side wall 14 along the length direction of the side wall 14), and the guide rail is provided with a first limiting card groove 12a and a second limiting card groove 12b corresponding to the first card-connecting position and the second card-connecting position, respectively, which can cooperate with the limiting card protrusion 9; When an external force is applied, causing the limiting protrusions 9 on both sides of the detection card 11 to be positioned at the second limiting groove 12b and engage with it, the detection card 11 engages with the engagement opening 8 at the second engagement position. At this time, the detection card 11 is merely engaged with the multi-channel microfluidic sample application device, and the tip 6 of the puncture tube 5 does not pierce the thin film material covered by the micropillar on the detection card 11. Furthermore, there is a certain distance e between the tip 6 and the thin film of the micropillar 13, which is slightly less than or equal to the first engagement position and the second engagement position (or the distance between the first limiting groove 12a and the second limiting groove 12b). When the limiting protrusion 9 disengages from the second limiting slot 12b under the action of an external force, the detection card 11 can move along the guide rail toward the puncture tube 5. When the limiting protrusion 9 on the detection card 11 moves to the first limiting slot 12a under the action of an external force and engages with the first limiting slot 12a, the detection card 11 engages with the engagement opening 8 at the first engagement position. At this time, the tip 6 of the puncture tube 5 does not pierce the thin film material covered by the micropillar on the detection card 11.

[0071] In other embodiments, a limiting protrusion 9 is provided on one or both sides of the detection card 11. Correspondingly, the snap-fit ​​opening 8 includes a guide rail for providing a moving path for the detection card (specifically, the two side walls 14 extending from the main body, or the guide rail is provided on the two side walls 14 along its length direction). The guide rail is provided with a first limiting slot 12a that can cooperate with the limiting protrusion 9 corresponding to the first snap-fit ​​position. The end of the limiting protrusion 9 is fixedly connected to the second snap-fit ​​position, and the connection is provided with a breakable break line (of course, a connecting piece that can be fixedly connected to the limiting protrusion 9 and is easy to break can also be provided at the second snap-fit ​​position). In the initial state, the end of the limiting card protrusion 9 is fixedly connected to the guide rail, so that the detection card is fixedly connected at the second snap-fit ​​position; similarly, at this time, the tip 6 of the puncture tube 5 does not pierce the thin film material covered by the micropillar on the detection card 11. When the limiting card protrusion 9 is disconnected from the guide rail under the action of an external force, the detection card can move along the guide rail towards the puncture tube; and when the limiting card protrusion 9 moves to the first limiting card groove 12a under the action of an external force and cooperates with the first limiting card groove 12a, the detection card and the carding opening are engaged in the first engagement position; at this time, the tip 6 of the puncture tube 5 pierces the thin film material covered by the micropillar on the detection card 11.

[0072] Example 3 Based on the multi-channel microfluidic sampling device of Embodiment 1 above, the present invention also provides another multi-channel microfluidic sampling assembly, which includes the multi-channel microfluidic sampling device of the above embodiment and a detection card; the difference is that, see [link to documentation]. Figure 5 In some embodiments, the multi-channel microfluidic sampling device is provided with a snap-fit ​​opening that can be inserted into the detection card, and the detection card is provided with a second snap-fit ​​position and a first snap-fit ​​position at intervals on one or both sides along the direction that gradually moves away from the micropillar.

[0073] The detection card 11 is installed at the second snap-fit ​​position in a manner that allows it to move relative to the snap-fit ​​opening 8; at this time, the tip 6 of the puncture tube 5 on the multi-channel microfluidic sampling device does not pierce the sealing film covered by the opening end of the microcolumn 13 on the detection card 11 (that is, the tip 6 is at a certain distance from the opening end of the microcolumn 13).

[0074] When an external force is applied, the detection card 11 moves relative to the snap-fit ​​opening 8, and when the snap-fit ​​opening 8 snaps into the detection card 11 at the first snap-fit ​​position, the tips 6 of the multiple puncture tubes 5 on the multi-channel microfluidic sample application device pierce the sealing membrane covered by the openings of the multiple micropillars on the detection card 11.

[0075] See Figure 5In some embodiments, the detection card 11 has a first limiting slot 12a and a second limiting slot 12b respectively provided on one or both sides corresponding to the first and second locking positions; correspondingly, the locking opening 8 includes a guide rail for providing a sliding path for the detection card 11 (specifically, the two side walls 14 extending from the body, or the guide rail is provided on the two side walls 14 along its length direction), and the guide rail is provided with a limiting protrusion 9 that can cooperate with the first limiting slot 12a and the second limiting slot 12b; When an external force is applied, causing the limiting card protrusion 9 to engage with the second limiting card groove 12b on the detection card 11, the detection card 11 and the engagement opening 8 engage at the second engagement position. At this time, the tip 6 of the puncture tube 5 on the multi-channel microfluidic sampling device does not pierce the thin film material on the micropillar on the detection card 11. Of course, the micropillar is still a certain distance away from the tip 6 of the puncture tube 5. When the limiting card protrusion 9 is disengaged from the second limiting card groove 12b under the action of an external force, the detection card 11 can move along the guide rail toward the puncture tube 5; and when the first limiting card groove 12a on the detection card 11 moves to the position of the limiting card protrusion 9 on the guide rail and cooperates with the limiting card protrusion 9, the detection card 11 is engaged with the engagement opening 8 at the first engagement position, at which time the tip 6 of the puncture tube 5 pierces the thin film material on the micropillar on the detection card 11.

[0076] In other embodiments, the snap-fit ​​opening 8 includes: a guide rail for providing a moving path for the detection card 11 (specifically, the two side walls 14 extending from the body, or the guide rail is provided on the two side walls 14 along its length direction), and a limiting snap-fit ​​protrusion 9 is provided on the guide rail; correspondingly, a first limiting snap-fit ​​groove 12a that can cooperate with the limiting snap-fit ​​protrusion is provided on one or both sides of the detection card 11 at the first snap-fit ​​position, and the end of the limiting snap-fit ​​protrusion 9 (i.e. the end away from the guide rail and corresponding to the detection card 11) is fixedly connected to the second snap-fit ​​position on the detection card 11, and the connection is provided with an easily breakable break line; In the initial state, the limiting protrusion 9 on the snap-fit ​​opening 8 is fixedly connected to the detection card 11 at the second snap-fit ​​position. At this time, the tip 6 of the puncture tube 5 does not pierce the film material on the micropillar on the detection card 11. In specific implementation, at this time, the tip 6 of the puncture tube 5 actually has a certain distance e between it and the micropillar. Specifically, this distance only needs to be sufficient to ensure that the tip 6 cannot pierce the film at the opening end of the micropillar. When the limiting card protrusion 9 is disconnected from the guide rail under the action of an external force, the detection card 11 can move along the guide rail toward the direction of the puncture tube 5; and when the first limiting card groove 12a on the detection card 11 moves to the position of the limiting card protrusion 9 on the guide rail under the action of an external force and cooperates with the limiting card protrusion 9, the detection card 11 and the locking opening 8 are locked at the first locking position, and at this time the tip 6 of the puncture tube 5 pierces the thin film material on the micropillar on the detection card 11.

[0077] Example 4 This paper provides a multi-channel microfluidic sample loading device, comprising: a body; a sample loading port located on the surface of the body for receiving liquid samples; multiple capillary sample loading channels disposed inside the body, the first end of each capillary sample loading channel communicating with the sample loading port, wherein when the liquid sample is added to the sample loading port, the liquid sample fills the capillary sample loading channel through capillary action; and multiple puncture tubes disposed on one side of the body and extending into the body, wherein the first end of each puncture tube located inside the body communicates with the second end of each capillary sample loading channel, and the second end of each puncture tube located outside the body is a pointed tip. The inner diameter of the puncture tube or the inner diameter of the puncture tube at the contact point with the capillary sampling channel is larger than the inner diameter of the capillary sampling channel, so that the liquid sample will not continue to enter the puncture tube through capillary action.

[0078] In some embodiments, the body is sheet-like or plate-like, and the plurality of capillary sampling channels are arranged horizontally inside the body.

[0079] In some implementations, the second end of the capillary sampling channel is connected to the first end of the puncture tube through a connecting channel, which is perpendicular to the plane in which the plurality of capillary sampling channels are located.

[0080] In some implementations, the connecting channel is a capillary channel.

[0081] In some embodiments, the multichannel microfluidic sampling device further includes two sidewalls extending from both sides of the body to form snap-fit ​​openings for insertion with a detection card. When a detection card with multiple micropillars and a sealing membrane is pushed into the snap-fit ​​openings, the tips of the multiple puncture tubes puncture the sealing membrane covering the multiple micropillars.

[0082] In some implementations, the sidewall is provided with a limiting protrusion that cooperates with the limiting slot on the detection card.

[0083] In some embodiments, the body is further provided with a waste liquid tank communicating with the sample loading port. When there is too much liquid sample in the sample loading port or under the action of centrifugal force, the liquid sample in the sample loading port can flow into the waste liquid tank.

[0084] In some implementations, the waste liquid tank is provided with a baffle to restrict the flow of the liquid sample back to the sample loading hole.

[0085] In some implementations, the inner diameter of the capillary sampling channel is 0.5 mm, and the inner diameter of the connecting channel is 0.8 mm.

[0086] On the other hand, this paper provides the application of the multi-channel microfluidic sampling device for sampling blood typing cards.

[0087] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0088] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A multi-channel microfluidic sample delivery assembly, characterized in that, include: A multi-channel microfluidic sampling device and a detection card, wherein the multi-channel microfluidic sampling device includes: ontology, A sample loading orifice with a conical structure for receiving liquid samples, wherein the sample loading port of the orifice is located on the first surface of the body; Multiple capillary sampling channels are spaced apart inside the main body, and the first end of each capillary sampling channel communicates with the sample loading hole; when the liquid sample is added to the sample loading hole, the liquid sample fills the multiple capillary sampling channels through capillary action. Multiple puncture tubes are spaced apart on the first side of the body and extend into the body. The first ends of the multiple puncture tubes extending into the body are respectively connected to the second ends of the multiple capillary sampling channels. The second ends of the multiple puncture tubes extending into the outside of the body are pointed tips for puncture. Wherein, the inner diameter of the puncture tube or the inner diameter of the puncture tube at the contact point with the capillary sampling channel is larger than the inner diameter of the capillary sampling channel, so that the liquid sample will not continue to enter the puncture tube through capillary action. The main body also includes a waste liquid tank communicating with the sample loading port. When there is too much liquid sample in the sample loading port or under centrifugal force, the liquid sample in the sample loading port can flow into the waste liquid tank. The waste liquid tank is equipped with a baffle to prevent the liquid sample from flowing back into the sample loading port. The multi-channel microfluidic sampling device is provided with a snap-fit ​​opening that can be inserted into the detection card, and the sidewall of the snap-fit ​​opening is provided with a first snap-fit ​​position and a second snap-fit ​​position at intervals along the extension direction of the sidewall. The detection card is mounted at the second card-connecting position in a manner that allows it to move relative to the card-connecting opening; When the detection card is moved from the second snap-fit ​​position to the first snap-fit ​​position under the action of an external force, the tips of the multiple puncture tubes on the multi-channel microfluidic sampling device pierce the sealing membrane covered by the opening ends of the multiple microcolumns on the detection card. The detection card has a limiting protrusion on one or both sides. Correspondingly, the locking opening includes a guide rail for providing a moving path for the detection card, and the guide rail is provided with a first limiting slot that can cooperate with the limiting protrusion at the first locking position. The end of the limiting protrusion is fixedly connected to the guide rail at the second locking position, and the connection between the limiting protrusion and the second locking position is provided with a breakable line. When the limiting card protrusion is disconnected from the guide rail under the action of an external force, the detection card can move along the guide rail toward the direction of the puncture tube. When the limiting card protrusion moves to the first limiting card groove and cooperates with the first limiting card groove, the detection card and the carding opening are engaged at the first engaging position.

2. A multi-channel microfluidic sample delivery assembly, characterized in that, include: A multi-channel microfluidic sampling device and a detection card, wherein the multi-channel microfluidic sampling device includes: The body has a sample loading port with a conical structure for receiving liquid samples, and the sample loading port of the sample loading port is located on the first surface of the body; Multiple capillary sampling channels are spaced apart inside the main body, and the first end of each capillary sampling channel communicates with the sample loading hole; when the liquid sample is added to the sample loading hole, the liquid sample fills the multiple capillary sampling channels through capillary action. Multiple puncture tubes are spaced apart on the first side of the body and extend into the body. The first ends of the multiple puncture tubes extending into the body are respectively connected to the second ends of the multiple capillary sampling channels. The second ends of the multiple puncture tubes extending into the outside of the body are pointed tips for puncture. Wherein, the inner diameter of the puncture tube or the inner diameter of the puncture tube at the contact point with the capillary sampling channel is larger than the inner diameter of the capillary sampling channel, so that the liquid sample will not continue to enter the puncture tube through capillary action. The main body also includes a waste liquid tank communicating with the sample loading port. When there is too much liquid sample in the sample loading port or under centrifugal force, the liquid sample in the sample loading port can flow into the waste liquid tank. The waste liquid tank is equipped with a baffle to prevent the liquid sample from flowing back into the sample loading port. The multi-channel microfluidic sampling device is provided with a snap-fit ​​opening that can be inserted into the detection card, and the detection card is provided with a second snap-fit ​​position and a first snap-fit ​​position at intervals on one or both sides along the direction that gradually moves away from the microcolumn. The detection card is mounted at the second card-connecting position in a manner that allows it to move relative to the card-connecting opening; When the detection card is moved from the second snap-fit ​​position to the first snap-fit ​​position under the action of an external force, the multiple puncture tubes on the multi-channel microfluidic sampling device puncture the sealing film covering the opening ends of the multiple microcolumns on the detection card. The snap-fit ​​opening includes: a guide rail for providing a moving path for the detection card, and a limiting snap protrusion is provided on the guide rail; correspondingly, one or both sides of the detection card are provided with a first limiting snap groove that can cooperate with the limiting snap protrusion at the first snap-fit ​​position; wherein, the end of the limiting snap protrusion is fixedly connected to the second snap-fit ​​position on the detection card, and a breakable break line is provided at the connection between the limiting snap protrusion and the second snap-fit ​​position; When an external force causes the limiting card protrusion to disconnect from the detection card, the detection card can move along the guide rail toward the puncture tube; and when the first limiting card groove moves to the position of the limiting card protrusion and cooperates with the limiting card protrusion, the detection card and the locking opening are locked at the first locking position.

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