Multi-channel microfluidic sampling device, assembly and application thereof
The multi-channel microfluidic sample loading device uses capillary action and centrifugal force to realize quantitative sample loading of the detection card, solving the problems of complex sample loading operations and cross-contamination in the prior art, and achieving automation and cost reduction effects.
Patent Information
- Application Number
- CN202180078873.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-09-07
- Publication Date
- 2025-05-13
- Estimated Expiration
- 2041-09-07
AI Technical Summary
The existing detection card sample loading device is complex in operation, which easily leads to cross-contamination, and it is difficult to achieve quantitative sample loading, especially when the inner diameter of the reagent card sample loading port is less than 1-2mm, manual sample loading is difficult.
A multi-channel microfluidic sample loading device is adopted, which includes a loading hole, a capillary sample channel and a puncture tube. Quantitative sample loading is achieved through capillary action and centrifugal force to avoid cross-contamination.
Multi-channel sample loading of the detection card is realized, with simple operation, avoiding cross-contamination, which is conducive to the automation of sample loading and testing, and reducing manufacturing and testing costs.
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Figure CN116490281B_ABST
Abstract
Description
[0001] This application claims priority to Chinese application CN2020114314743 filed on December 10, 2020, which is incorporated by reference in its entirety. Technical Field
[0002] The present application relates to a test card loading device, in particular to a multi-channel microfluidic loading device suitable for loading samples simultaneously to multiple loading ports on a test card and a loading component having the loading device. The present application also relates to the application of the test card loading device and the component. Background Art
[0003] Various test cards (such as blood type test cards) often use soft film materials (such as aluminum foil, plastic film) to seal the fillers (such as various reagents and / or gel microspheres) therein. When in use, it is necessary to tear off or puncture this layer of sealing film before adding samples to the test card. For example, traditional blood type cards need to be punched with a hole puncher before use, which easily causes cross contamination; for blood type cards including multiple microcolumns, each blood type card needs to be sampled multiple times, which is cumbersome to operate and difficult to ensure accurate and equal amount of sample addition. In addition, with the miniaturization of various reagent cards, when the inner diameter of the sample addition port on the reagent card is only 1-2 mm or smaller, manual sample addition is also difficult to perform.
[0004] Therefore, some researchers have designed and improved the operations related to the sample addition of the reagent card. For example, the utility model patent with patent announcement number CN204359800U discloses a blood type reagent card piercing device, including: multiple thorn edges and barcode guns all arranged on a frame, and a manipulator used in conjunction with the thorn edges, the barcode gun is arranged on the side of multiple thorn edges, one end of the thorn edge is fixed on the frame, and the other end has a thorn tip, the thorn tip faces the same direction, the thorn edge is arranged in several rows, each row has a different number of thorn edges, and the thorn edges in the same row are arranged at equal intervals. Although this technical solution can achieve the purpose of piercing and adding samples, its overall manufacturing cost is high, the operation is complicated, and there is still the problem of cross contamination.
[0005] For another example, the utility model patent with patent announcement number CN210142129U discloses a microcolumn gel blood type detection card poker, comprising: a barbed edge for poking holes, a mounting base for setting the barbed edge, and a handheld portion for holding the poker; the handheld portion comprises two side surfaces arranged in parallel along the length direction of the mounting base, and the two side surfaces are arranged on the same side of the mounting base as the barbed edge and are perpendicular to the mounting base; the internal distance between the two side surfaces is equal to the width of the microcolumn gel card. By setting up multiple pokers, different detection tubes (microcolumns) can be poked through different barbed edges, avoiding cross contamination when the same barbed edge punctures different detection tubes, but it can only puncture when in use, and cannot play a role in quantitative sampling.
[0006] For quantitative sampling, some researchers have proposed new microfluidic chips. For example, the invention patent application with the Chinese patent publication number CN111604098A discloses two types of sample loading microfluidic chips. The first type is to set the sample loading hole on the surface of the body, and the second type is to set the sample loading hole on the side of the body. Both types are provided with sampling channels, quantitative channels, shut-off valves, reaction channels and waste liquid chambers inside the body. Among them, the sampling channel is used to transport samples to each quantitative channel and waste liquid chamber; the quantitative channel is connected to the downstream reaction channel through the shut-off valve; the reaction channel is used to carry out detection reactions, and reaction reagents can be pre-loaded, or the sample to be detected can be transported to the reaction chamber; the waste liquid chamber is used to accommodate excess samples to be detected. That is, both microfluidic chips realize quantitative sampling through the capillary sampling channel connected to the sample loading hole. These two sampling methods still have problems such as cross-infection and high detection costs. Summary of the invention
[0007] The object of the present invention is to provide a multi-channel microfluidic sample loading device and a sample loading component thereof, so as to partially solve or alleviate the above-mentioned deficiencies in the prior art, and to be able to load samples on multiple channels of a detection card, with simple operation, and avoid cross contamination, which is conducive to the automation of loading and detection.
[0008] In order to solve the above-mentioned technical problems, the present invention specifically adopts the following technical solutions:
[0009] A first aspect of the present invention is to provide a multi-channel microfluidic sampling device, comprising:
[0010] ontology;
[0011] A loading hole for receiving a liquid sample, wherein a loading port (or opening) of the loading hole is located on a first surface (e.g., an upper surface) of the body;
[0012] A plurality of capillary sampling channels are arranged at intervals inside the body, wherein the first ends of the capillary sampling channels are communicated with the loading hole, and when the liquid sample is added to the loading hole, the liquid sample fills the plurality of capillary sampling channels through capillary action;
[0013] A plurality of puncture tubes are arranged at intervals on the first side of the body and extend into the interior of the body, wherein the first ends of the plurality of puncture tubes located inside the body are respectively communicated with the second ends of the plurality of capillary sampling channels, and the second ends of the plurality of puncture tubes located outside the body are sharp ends for puncture.
[0014] The inner diameter of the puncture tube or the inner diameter of the contact point between the puncture tube and 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.
[0015] In some embodiments of the present invention, the body is sheet-shaped or plate-shaped, and the plurality of capillary sampling channels are arranged inside the body at intervals along the length direction of the body.
[0016] In some embodiments of the present invention, the second end of the capillary sampling channel is communicated with the first end of the puncture tube through a connecting channel, and the connecting channel is perpendicular to the plane where the multiple capillary sampling channels are located.
[0017] In some embodiments of the present invention, the connecting channel is a capillary channel.
[0018] In some embodiments of the present invention, the multi-channel microfluidic loading device further comprises: two snap-in openings formed by side walls extending from both sides of the body and used for plugging with a test card; when the test card is pushed into the snap-in openings, the pointed ends of the multiple puncture tubes pierce the sealing film covering the open ends of the multiple microcolumns on the test card.
[0019] In some embodiments, the side wall is provided with a limiting protrusion that can cooperate with the limiting groove on the detection card; or, the side wall is provided with a limiting groove that can cooperate with the limiting protrusion on the detection card.
[0020] In some embodiments of the present invention, a waste liquid tank connected to the loading hole is further provided inside the body. When there is too much liquid sample in the loading hole or under the action of centrifugal force, the liquid sample in the loading hole can flow into the waste liquid tank.
[0021] In some embodiments of the present invention, a baffle is disposed in the waste liquid tank to limit the liquid sample from flowing back to the loading hole.
[0022] 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.
[0023] 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.
[0024] 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 over the top of the sheet-like structure due to excessive liquid sample during the loading process, the overflowed liquid sample enters the waste liquid tank.
[0025] In some embodiments of the present invention, the blocking sheet is subjected to a hydrophobic treatment.
[0026] In some embodiments of the present invention, a hydrophobic layer is disposed on the baffle.
[0027] In some embodiments of the present invention, the loading hole has a conical structure.
[0028] In some embodiments of the present invention, the first ends of the plurality of capillary channels are distributed along the circumference of the loading hole, and preferably, symmetrically distributed along the circumference.
[0029] In some embodiments of the present invention, the capillary channel is covered with a hydrophilic film layer.
[0030] A second aspect of the present invention is to provide a multi-channel microfluidic loading assembly, comprising any one of the multi-channel microfluidic loading devices described above, and a test card, wherein the multi-channel microfluidic loading device is provided with a clamping opening that can be plugged into the test card, and a first clamping position and a second clamping position are provided on a side wall of the clamping opening at intervals along an extension direction of the side wall;
[0031] Wherein, the detection card is installed at the second clamping position in a manner that it can move relative to the clamping opening;
[0032] When the test card is moved from the second clamping position to the first clamping position under the action of an external force, the pointed ends of the multiple puncture tubes on the multi-channel microfluidic loading device pierce the sealing film covered by the open ends of the multiple microcolumns on the test card.
[0033] In some embodiments of the present invention, a limiting clamping protrusion is respectively provided on one side or both sides of the detection card, and accordingly, the clamping opening comprises: a guide rail for providing a moving path for the detection card, and a first limiting clamping groove and a second limiting clamping groove which can cooperate with the limiting clamping protrusion are respectively provided on the guide rail corresponding to the first clamping position and the second clamping position;
[0034] When the limit clamping protrusion cooperates with the second limit clamping groove, the detection card is clamped with the clamping opening at the second clamping position;
[0035] When the limiting clamping protrusion is disengaged from the second limiting clamping 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 clamping protrusion is moved to the first limiting clamping slot and cooperates with the first limiting clamping slot under the action of an external force, the detection card is clamped with the clamping opening at the first clamping position.
[0036] In some embodiments of the present invention, a limiting clamping protrusion is respectively provided on one side or both sides of the detection card, and correspondingly, the clamping opening includes: a guide rail for providing a moving path for the detection card, and the guide rail is respectively provided with a first limiting clamping groove that can cooperate with the limiting clamping protrusion at the positions corresponding to the first clamping positions; wherein the end of the limiting clamping protrusion is fixedly connected to the position corresponding to the second clamping position on the guide rail, and an easily breakable breaking line is provided at the connection between the limiting boss and the second clamping position (that is, in the initial state, the limiting clamping protrusion is fixedly connected to the second clamping position on the guide rail);
[0037] When the limit clamping protrusion is disconnected from the guide rail under the action of external force, the detection card can move along the guide rail toward the puncture tube; and when the limit clamping protrusion moves to the first limit clamping groove under the action of external force and cooperates with the first limit clamping groove, the detection card is clamped with the clamping opening at the first clamping position.
[0038] The third aspect of the present invention is to provide another multi-channel microfluidic loading assembly, which comprises any one of the multi-channel microfluidic loading devices described above, and a detection card, wherein the multi-channel microfluidic loading device is provided with a clamping opening that can be plugged with the detection card, and one side or both sides of the detection card are provided with a second clamping position and a first clamping position at intervals in a direction gradually away from the microcolumn;
[0039] Wherein, the detection card is installed at the second clamping position in a manner that it can move relative to the clamping opening;
[0040] When the test card is moved from the second clamping position to the first clamping position under the action of an external force, the multiple puncture tubes on the multi-channel microfluidic loading device pierce the sealing film covered by the open ends of the multiple microcolumns on the test card.
[0041] In some embodiments of the present invention, a first limit card slot and a second limit card slot are respectively provided on one side or both sides of the detection card corresponding to the first clamping position and the second clamping position; accordingly, the clamping opening comprises: a sliding guide rail for providing a sliding path for the detection card, and a limit card protrusion that can cooperate with the first limit card slot and the second limit card slot is provided on the sliding guide rail;
[0042] When the limit clamping protrusion cooperates with the second limit clamping groove, the detection card is clamped with the clamping opening at the second clamping position;
[0043] When the limiting clamping protrusion is disengaged from the second limiting clamping slot under the action of an external force, the detection card can move along the guide rail toward the puncture tube; and when the first limiting clamping slot is moved to the position of the limiting clamping protrusion under the action of an external force and cooperates with the limiting clamping protrusion, the detection card is clamped with the clamping opening at the first clamping position.
[0044] In some embodiments of the present invention, the clamping opening includes: a guide rail for providing a moving path for the detection card, and a limit clamping protrusion is provided on the guide rail; accordingly, a first limit clamping groove that can cooperate with the limit clamping protrusion is provided on one side or both sides of the detection card corresponding to the first clamping position; wherein the end of the limit clamping protrusion is fixedly connected to the second clamping position on the detection card, and an easy-to-break breaking line is provided at the connection between the limit clamping protrusion and the second clamping position (that is, in the initial state, the limit clamping protrusion and the detection card are fixedly connected to the second clamping position);
[0045] When the limit clamping protrusion is disconnected from the detection card under the action of an external force, the detection card can move along the guide rail toward the puncture tube; and when the first limit clamping slot is moved to the position of the limit clamping protrusion under the action of an external force and cooperates with the limit clamping protrusion, the detection card is clamped with the clamping opening at the first clamping position.
[0046] The fourth aspect of the present invention is to provide the application of the above-mentioned multi-channel microfluidic sample loading device or multi-channel microfluidic sample loading component in loading samples on a blood type detection card.
[0047] Beneficial effects:
[0048] The multi-channel microfluidic loading device provided by the present invention cleverly combines capillary action and centrifugal force, can realize multi-channel loading of the test card, is easy to operate, avoids cross contamination, and is conducive to the automation of loading and detection. On the other hand, compared with the prior art of loading from the side, in order to ensure that the microfluidic chip is always in a vertical state during the transportation process and the detection process, it is necessary to adjust or improve the structure of the next operation equipment such as the transportation equipment, centrifuge, etc., which leads to the problem of increased manufacturing and detection costs; the multi-channel microfluidic loading device provided by the present invention does not need to adjust or improve the existing equipment during the loading, transportation and next detection process, which greatly reduces the manufacturing and detection costs. That is to say, the multi-channel microfluidic loading device provided by the present invention has a wider range of application and better versatility.
[0049] The multi-channel microfluidic sample loading assembly provided by the present invention can directly connect the test card and the sample loading device at the second connecting position by respectively setting the first and second connecting positions on the sample loading device, or respectively setting the first and second connecting positions on the test card, so that the test card and the sample loading device can be directly connected at the second connecting position (that is, the test card and the sample loading device are integrated into one). At this time, since the tip end of the puncture tube on the sample loading device maintains a certain safety distance from the microcolumn on the test card, it is possible to use the sample loading device in the scene where sample loading and quantitative sample splitting are not required, such as carrying or transporting. In the scene, the one-to-one correspondence between the puncture tube on the sample loading device and the microcolumn on the test card is ensured, and the sealing of the microcolumn on the test card is also ensured; when the scene of sample loading and quantitative sample splitting is required, the test card can be moved to be connected with the sample loading device at the first clamping position. At this time, the pointed end of the puncture tube on the sample loading device pierces the sealing film, and because each puncture tube on the sample loading device corresponds to a microcolumn (that is, the puncture tube corresponds to the microcolumn one by one), quantitative sample splitting is achieved while avoiding cross infection. The multi-channel microfluidic sample loading structure provided by the present invention is simple and easy to carry or transport. BRIEF DESCRIPTION OF THE DRAWINGS
[0050] In order to more clearly illustrate the present invention, the following will briefly introduce the drawings required for the description of the specific embodiments. In all the drawings, similar elements or components are generally identified by similar reference numerals. In the drawings, each element or component is not necessarily drawn according to the actual scale.
[0051] Figure 1 It is a schematic diagram of the three-dimensional structure of the multi-channel microfluidic sample loading device of the present invention, showing a part of the structure of its upper surface;
[0052] Figure 2 is a schematic diagram of the three-dimensional structure of the multi-channel microfluidic sample loading device of the present invention, showing the internal structure close to its lower surface;
[0053] Figure 3is a schematic diagram of the structure of the multi-channel microfluidic sample loading device of the present invention, showing the internal structure close to its lower surface;
[0054] Figure 4 Displays the state of the multi-channel microfluidic sample loading device of the present invention before being plugged into the test card;
[0055] Figure 5 Display the state of the multi-channel microfluidic sample adding device of the present invention after being plugged into the detection card;
[0056] Figure 6 It is a schematic diagram of the three-dimensional structure of a detection card used in conjunction with the multi-channel microfluidic sample loading device of the present invention;
[0057] Figure 7 This is a schematic structural diagram of an initial state of a multi-channel microfluidic sample loading assembly according to an exemplary embodiment of the present invention.
[0058] In the figure, 1, main body; 2, loading hole; 3, capillary sampling channel; 4, connecting channel; 5, puncture tube; 6, pointed end; 7, waste liquid tank; 8, snap-on opening; 9, limit cam; 10, baffle; 11, detection card; 12, limit slot (first limit slot 12a, second limit slot 12b); 13, micro column; 14, side wall. DETAILED DESCRIPTION
[0059] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.
[0060] Herein, suffixes such as "module", "component" or "unit" used to represent elements are only used to facilitate the description of the present invention, and have no specific meanings by themselves. Therefore, "module", "component" or "unit" can be used mixedly.
[0061] In this document, the terms "upper", "lower", "inner", "outer", "front", "rear", "one end", "the other end" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be constructed and operate in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.
[0062] In this document, unless otherwise clearly specified or limited, the terms "installed", "provided with", "connected", etc. should be understood in a broad sense. For example, "connected" 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, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this utility model can be understood according to specific circumstances.
[0063] Since the multi-channel microfluidic loading device provided in this article involves centrifugation operation when used, for the convenience of description, the end relatively far away from the centrifugal shaft during centrifugation is called the distal end, and the end relatively close to the centrifugal shaft is called the proximal end.
[0064] In this article, the surface on one side where the opening of the loading hole (or loading port) of the multi-channel microfluidic loading device is located is called the upper surface (or first surface), and the other side is called the lower surface (or second surface).
[0065] Unless otherwise specified, when a structure is mentioned as being "inside" the multi-channel microfluidic loading device, it means that it is surrounded by the main body material or other materials of the multi-channel microfluidic loading device and is not directly in contact with the external space.
[0066] In this article, for the purpose of distinction, "loading" is generally used to describe the process of the multi-channel microfluidic loading device of the present invention itself accepting a sample, and "adding" is used to describe the process of the detection card accepting a sample.
[0067] Embodiment 1
[0068] refer to Figure 1-5 The multi-channel microfluidic loading device body 1 in an exemplary embodiment of the present invention 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 several millimeters.
[0069] In an exemplary embodiment of the present invention, the multi-channel microfluidic loading device is provided with a loading hole 2 on the body 1, the opening (i.e., loading port) being located on the upper surface (or first surface) of the body 1. Multiple (i.e., two or more) capillary sampling channels 3 are arranged at intervals inside the body 1 along the plane direction of the body 1 (i.e., the plane where the length and width dimensions are located, or the horizontal direction), the first ends of these capillary sampling channels 3 are connected to the loading hole 2, and the other ends (i.e., the second ends) are evenly spaced and distributed at the far end of the body 1. Multiple communication channels 4 are arranged inside the body 1 substantially along the thickness direction (i.e., perpendicular to the plane where the capillary sampling channels 3 are located), which are respectively connected to the other ends (i.e., the second ends) of each capillary sampling channel 3. Multiple puncture tubes 5 extending to the inside of the body 1 are evenly spaced at the far end side of the body 1 (i.e., the first side close to the second ends of the capillary sampling channels 3). The first end of the puncture tube 5 located inside the body 1 is connected to the communication channel 4, and the other end (i.e., the second end extending to the outside of the body 1) is a sharp end 6 for puncture. In this way, the other end (i.e., the second end) of the capillary sampling channel 3 is communicated with the first end of the puncture tube 5 located inside the body 1 through the connecting channel 4. The capillary sampling channel 3 is a capillary channel, i.e., its inner diameter is suitable for the liquid sample to flow therein by capillary action, and is usually less than 1.5 mm, such as 0.5-1.2 mm or less.
[0070] In some embodiments, the above-mentioned connecting channel 4 can be a capillary channel, in which case it can be considered as 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 play a role in stopping flow. It should be understood that the connecting channel 4 and its arrangement along the thickness direction are also conducive to processing, and facilitate the communication between the capillary sampling channel 3 and the inner cavity of the puncture tube 5.
[0071] Figure 2-5 It can be considered as 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 sampling device of the present invention. In addition, for the convenience of processing (especially the capillary sampling channel 3) and / or hydrophilic treatment, it can also be processed into the illustrated structure first, and then the lower surface layer (such as a hydrophilic film) can be covered by pasting or bonding to achieve the same effect as these capillary sampling channels 3 and other structures located inside the body 1. Therefore, the multi-channel microfluidic sampling device, whether it is integrally injection molded or prepared by layered processing, or processed by layered processing but does not include the main structure of the lower surface layer, should be covered within the scope of protection of this application.
[0072] In some embodiments, further, in order to accommodate the excessive sample added to the loading well 2, a waste liquid tank 7 may be provided inside the body 1 near the loading well 2 (in the distal direction). Furthermore, in order to prevent the sample from entering the waste liquid tank 7 when there is not an excessive amount of sample and the sample in the waste liquid tank 7 from returning to the loading well 2, thereby causing cross infection, a baffle 10 may be provided in the waste liquid tank 7 near the loading well 2.
[0073] In some embodiments, the baffle 10 is a raised sheet at the bottom of the waste liquid tank 7. When loading samples, only when there is too much sample and it overflows over the upper end can the baffle 10 enter the waste liquid tank 7.
[0074] In addition, in order to facilitate the sample to enter 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 processed to have a hydrophobic property, such as adding a hydrophobic layer, to further prevent the sample entering the waste liquid tank 7 from returning to the loading hole 2.
[0075] In some embodiments, in order to facilitate the use with the detection card 11, a clamping opening 8 is provided at the far end of the body 1, and a limit clamping protrusion 9 is provided on the two opposite side walls 14 of the clamping opening 8. When the detection card 11 is pushed into the clamping opening 8, its two sides are respectively tightly matched with the two opposite side walls 14 of the clamping opening 8, and the limit clamping protrusion 9 is used for positioning.
[0076] The detection card 11 used in conjunction with the multi-channel microfluidic sample loading device of the exemplary embodiment of the present invention has a plurality of microcolumns 13 (or detection columns), see Figure 6 , the open ends of these micro-pillars 13 correspond to the positions of the pointed ends 6 of the puncture tubes 5. When the test card 11 is pushed into the snap-fit opening 8, the pointed ends 6 of each puncture tube 5 can pierce the thin film material covered on the open ends of each micro-pillar 13. The test card 11 corresponds to the limit clamping protrusion 9, and at least one set of limit clamping grooves 12 is arranged on both sides thereof. For example, when two sets of limit clamping grooves 12 are arranged on the test card 11, one set of limit clamping grooves 12 (i.e., the first limit clamping groove at the first snap-fit position on the test card) cooperates with the limit clamping protrusion 9, so that the pointed end 6 of the puncture tube 5 is in a state of piercing the thin film material, and the other set of limit clamping grooves 12 (i.e., the second limit clamping groove at the second snap-fit position on the test card) can be slightly higher. When they cooperate with the limit clamping protrusion 9, they only play the role of combining the test card 11 on the multi-channel microfluidic sample loading device of the present invention, and at this time, the pointed end 6 of the puncture tube 5 does not pierce the thin film material on the test card 11.
[0077] See also Figure 4 and Figure 5When in use, the test card 11 is inserted into the card opening 8 and pushed upward with force, so that the pointed end 6 of each puncture tube 5 just pierces the covering film material on each microcolumn 13. Then, a liquid sample (such as blood) is added to the upper sampling hole 2, and the sample enters each capillary sampling channel 3 under capillary action.
[0078] When the communication channel 4 is a capillary channel, the liquid sample also enters the communication channel 4; when the communication 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 portion in contact with the communication channel 4 can usually be set large enough so that even if the communication channel 4 is a capillary channel, the liquid sample will not continue to enter it by capillary action.
[0079] After loading, the multi-channel microfluidic loading device of the present invention with the test card 11 is placed in the centrifugal slot of the centrifuge for centrifugation. Under the action of centrifugal force, the remaining sample in the loading hole 2 will quickly flow into the waste liquid tank 7; the sample in the capillary sampling channel 3 and the connecting channel 4 (when it is a capillary channel) will enter the microcolumns 13 of the test card 11 through the puncture tube 5 to achieve the loading of the test 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 hole 2.
[0080] The use process is described here in chronological order. Those skilled in the art will appreciate that it is not necessary to perform the operations in this order. For example, the multi-channel microfluidic loading device of the present invention may be placed in a centrifuge, and then the test card may be plugged in and sampled, or sampled and the test card may be loaded and plugged in sequentially.
[0081] Obviously, the length and / or inner diameter of each capillary sampling channel 3 and the connecting channel 4 (when it is a capillary channel) can be adjusted to ensure that the sample loading amount of each microcolumn 13 is the same or different.
[0082] In some embodiments, the sample loading hole 2 adopts a tapered structure with a large top and a small bottom. The large loading port is easy to align the sample, and the small bottom makes it easier for the sample to contact the capillary sampling channel 3, which speeds up the sample splitting speed compared with the sample loading method in the prior art.
[0083] Further, in some embodiments, see Figure 4 and Figure 5 Since the first ends of the plurality of capillary sampling channels 3 are distributed along the circumference of the loading hole 2 (for example, symmetrically distributed) and are directly connected to the bottom of the loading hole 2, when adding samples, the samples can enter each capillary sampling channel 3 almost simultaneously, thereby further accelerating the sampling speed. Compared with the prior art, the samples need to enter the quantitative channels in sequence according to the arrangement order of the component channels along the length direction of the body, which greatly increases the sampling efficiency and detection efficiency.
[0084] It is understandable that when the card slot on the centrifuge is suitable for simultaneously fixing the multi-channel microfluidic loading device and the detection card of the present invention, the multi-channel microfluidic loading device of the present invention may not include the card connection opening 8, because when both are fixed on the centrifuge at the same time, the puncture operation can be completed on the centrifuge.
[0085] It is understandable that the number of capillary sampling channels 3 of the multi-channel microfluidic sampling device of the present invention can be dozens or more, and 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.
[0086] The multi-channel microfluidic sample loading device of the exemplary embodiment of the present invention is particularly suitable for loading samples on gel microcolumn blood typing cards. When performing blood typing, the gel microcolumn blood typing card itself needs to be centrifuged to detect the cell agglutination reaction. Therefore, by cooperating with the multi-channel microfluidic sample loading device of the exemplary embodiment of the present invention, centrifugation is continued after loading the sample, and the entire process of loading, splitting, loading and detecting can be simply realized on a centrifuge, which is suitable for automated operation.
[0087] The following is an example of a multi-channel microfluidic loading device of an exemplary embodiment of the present invention, which is prepared for loading samples on a micro blood type detection card with 6 microcolumns: the main body of the multi-channel microfluidic loading device of the present invention is made of polycarbonate (PC) material, with a thickness of about 4.5 mm, and a hydrophilic film layer is pasted to cover structures such as capillary sampling channels, so that aqueous liquids such as blood can flow therein. The loading hole is a conical structure with a mouth diameter of 5 mm and a bottom diameter of 3 mm. The bottom surface of the waste liquid tank is rectangular with a size of 6 mmx2 mm, and the size of the baffle in the waste liquid tank is 2 mmx0.5 mm and a thickness of 0.5 mm. Six capillary sampling channels are set, 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.
[0088] Embodiment 2
[0089] Based on the multi-channel microfluidic sample loading device in the above embodiment 1, the present invention further provides a multi-channel microfluidic sample loading component, which includes: the multi-channel microfluidic sample loading device in the above embodiment 1, and a detection card; the difference is that, see Figure 7 In some embodiments, a first clamping position and a second clamping position are provided on a side wall of the clamping opening of the multi-channel microfluidic loading device at intervals along a direction extending from the side wall (i.e., extending along a distal end, or gradually approaching a detection card);
[0090] The test card 11 is installed at the second clamping position in a manner that it can move relative to the clamping opening 8. At this time, the test card 11 is only installed on the multi-channel microfluidic loading device, and the pointed end 6 of the puncture tube 5 on the multi-channel microfluidic loading device does not pierce the sealing film covered by the opening end of the microcolumn on the test card 11;
[0091] When the test card 11 is gradually moved from the second engaging position to the first engaging position under the action of an external force, the multiple puncture tubes on the multi-channel microfluidic loading device pierce the sealing film covered by the open ends of the multiple microcolumns 13 on the test card 11 .
[0092] In some embodiments, when the assembly leaves the factory (or is in the initial state), the test card 11 is installed at the second clamping position of the clamping opening on the multi-channel microfluidic loading device. For example, the limit clamp 9 provided on the test card 11 is fixedly connected to the second clamping position, 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 end of the puncture tube and the film on the microcolumn, and the distance is slightly less than or equal to the interval distance between the first clamping position and the second clamping position, that is, the puncture tube has not pierced the film on the microcolumn on the test card. When the connection is broken along the break line, and when the test card is moved from the second clamping position to the first clamping position (for example, the limit clamp convex and the limit clamping groove are buckled), the tip end of the puncture tube can pierce the film on the microcolumn.
[0093] In other embodiments, when the component leaves the factory, the detection card and the sample loading device are independent of each other, but after the first assembly, the detection card 11 is snapped onto the multi-channel microfluidic sample loading device (specifically, snapped onto the second snapping position of the snapping opening 8 by snap-fitting between the limiting snapping protrusion 9 and the limiting snapping groove). Similarly, at this time, there is a certain distance e between the pointed end of the puncture tube and the film on the microcolumn, and the distance is slightly less than or equal to the spacing distance between the first snapping position and the second snapping position; and when the detection card is moved from the second snapping position to the first snapping position (for example, the limiting snapping protrusion and the limiting snapping groove are snap-fitted) under the action of an external force, the pointed end of the puncture tube can pierce the film on the microcolumn.
[0094] See also Figure 7 In some specific embodiments, a limiting clamping protrusion 9 is respectively provided on both sides (of course, it can also be one side) of the detection card, and accordingly, the clamping opening 8 includes: a guide rail for providing a moving path for the detection card (specifically, the guide rail can be a side wall 14 formed by 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 a first limiting clamping groove 12a and a second limiting clamping groove 12b that can cooperate with the limiting clamping protrusion 9 are respectively provided on the guide rail at positions corresponding to the first clamping position and the second clamping position;
[0095] When the limiting clamping protrusions 9 on both sides of the test card 11 are located at the second limiting clamping groove 12b and matched with the second limiting clamping groove 12b under the action of external force, the test card 11 is clamped with the clamping opening 8 at the second clamping position; at this time, the test card 11 is only clamped on the multi-channel microfluidic loading device, and the pointed end 6 of the puncture tube 5 does not pierce the film material covered by the microcolumn on the test card 11, and there is a certain distance e between the pointed end 6 and the film of the microcolumn 13, which is slightly less than or equal to the first clamping position and the second clamping position (or the distance between the first limiting clamping groove 12a and the second limiting clamping groove 12b);
[0096] When the limiting clamping protrusion 9 is disengaged from the second limiting clamping 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 limiting clamping protrusion 9 on the detection card 11 is moved to the first limiting clamping groove 12a under the action of an external force and cooperates with the first limiting clamping groove 12a, the detection card 11 is clamped with the clamping opening 8 at the first clamping position; at this time, the pointed end 6 of the puncture tube 5 does not pierce the film material covered by the microcolumns on the detection card 11.
[0097] In other embodiments, a limiting clamping protrusion 9 is respectively provided on one side or both sides of the detection card 11, and accordingly, the clamping opening 8 includes: a guide rail for providing a moving path for the detection card (specifically, two side walls 14 extending from the body, or guide rails are provided on the two side walls 14 along the length direction thereof), and a first limiting clamping groove 12a that can cooperate with the limiting clamping protrusion 9 is provided on the guide rail corresponding to the first clamping position, and the end of the limiting clamping protrusion 9 is fixedly connected to the second clamping position, and a breaking line that is easy to break is provided at the connection (of course, a connecting piece that can be fixedly connected to the limiting clamping protrusion 9 and is easy to break can also be provided at the second clamping position);
[0098] In the initial state, the end of the limit clamping protrusion 9 is fixedly connected to the guide rail, so that the detection card is fixedly connected at the second clamping position; similarly, at this time, the pointed end 6 of the puncture tube 5 does not pierce the film material covered by the micro-column on the detection card 11;
[0099] When the limiting clamping protrusion 9 is disconnected from the guide rail under the action of external force, the detection card can move along the guide rail toward the puncture tube; and when the limiting clamping protrusion 9 moves to the first limiting clamping groove 12a under the action of external force and cooperates with the first limiting clamping groove 12a, the detection card is clamped with the clamping opening at the first clamping position; at this time, the pointed end 6 of the puncture tube 5 pierces the film material covered by the micro-columns on the detection card 11.
[0100] Embodiment 3
[0101] Based on the multi-channel microfluidic sample loading device of the above embodiment 1, the present invention also provides another multi-channel microfluidic sample loading component, which includes the multi-channel microfluidic sample loading device of the above embodiment and a detection card; the difference is that, see Figure 5 In some embodiments, the multi-channel microfluidic loading device is provided with a snap-in opening that can be plugged into the detection card, and a second snap-in position and a first snap-in position are spaced apart on one side or both sides of the detection card in a direction gradually away from the microcolumn.
[0102] Among them, the detection card 11 is installed at the second locking position in a manner that it can move relative to the locking opening 8; at this time, the pointed end 6 of the puncture tube 5 on the multi-channel microfluidic loading device does not pierce the sealing film covered by the opening end of the microcolumn 13 on the detection card 11 (that is, the pointed end 6 is at a certain distance from the opening end of the microcolumn 13).
[0103] When an external force acts on the test card 11 to move relative to the snap-in opening 8, and when the snap-in opening 8 and the test card 11 are snap-into a first snap-in position, the pointed ends 6 of the multiple puncture tubes 5 on the multi-channel microfluidic loading device pierce the sealing film covered by the open ends of the multiple microcolumns on the test card 11.
[0104] See also Figure 5 In some embodiments, a first limit card slot 12a and a second limit card slot 12b are respectively provided on one side or both sides of the detection card 11 corresponding to the first clamping position and the second clamping position; accordingly, the clamping opening 8 includes: a guide rail for providing a sliding path for the detection card 11 (specifically, two side walls 14 extending from the body, or guide rails are provided on the two side walls 14 along the length direction thereof), and a limit card protrusion 9 is provided on the guide rail that can cooperate with the first limit card slot 12a and the second limit card slot 12b;
[0105] When the limiting clamping protrusion 9 is matched with the second limiting clamping groove 12b on the detection card 11 under the action of external force, the detection card 11 is clamped with the clamping opening 8 at the second clamping position, and at this time, the sharp end 6 of the puncture tube 5 on the multi-channel microfluidic loading device does not pierce the film material on the microcolumn on the detection card 11; of course, the microcolumn is actually still at a certain distance from the sharp end 6 of the puncture tube 5;
[0106] When the limiting clamping protrusion 9 is disengaged from the second limiting clamping groove 12b under the action of external force, the detection card 11 can move along the guide rail toward the puncture tube 5; and when the first limiting clamping groove 12a on the detection card 11 moves to the position of the limiting clamping protrusion 9 on the guide rail and cooperates with the limiting clamping protrusion 9, the detection card 11 is clamped with the clamping opening 8 at the first clamping position, and at this time, the pointed end 6 of the puncture tube 5 pierces the thin film material on the microcolumn on the detection card 11.
[0107] In other embodiments, the clamping opening 8 includes: a guide rail for providing a moving path for the detection card 11 (specifically, two side walls 14 extending from the body, or guide rails are arranged on the two side walls 14 along the length direction thereof), and a limit clamping protrusion 9 is arranged on the guide rail; accordingly, a first limit clamping groove 12a that can cooperate with the limit clamping protrusion is arranged on one side or both sides of the detection card 11 corresponding to the first clamping position, and the end of the limit clamping protrusion 9 (i.e., the end away from the guide rail and corresponding to the detection card 11) is fixedly connected to the second clamping position on the detection card 11, and the connection is provided with a break line that is easy to break;
[0108] In the initial state, the limit clamping protrusion 9 on the clamping opening 8 is fixedly connected to the detection card 11 at the second clamping position. At this time, the sharp end 6 of the puncture tube 5 does not pierce the thin film material on the microcolumn on the detection card 11. In specific implementation, at this time, the sharp end 6 of the puncture tube 5 actually has a certain distance e from the microcolumn. Specifically, the distance only needs to satisfy that the sharp end 6 cannot pierce the thin film at the opening end of the microcolumn.
[0109] When the limiting clamping protrusion 9 is disconnected from the guide rail under the action of external force, the detection card 11 can move along the guide rail toward the puncture tube 5; and when the first limiting clamping groove 12a on the detection card 11 moves to the position of the limiting clamping protrusion 9 on the guide rail under the action of external force, and cooperates with the limiting clamping protrusion 9, the detection card 11 is clamped with the clamping opening 8 at the first clamping position, and at this time, the pointed end 6 of the puncture tube 5 pierces the thin film material on the microcolumn on the detection card 11.
[0110] Embodiment 4
[0111] The present invention provides a multi-channel microfluidic sampling device, which comprises: a body; a loading hole with an opening located on the surface of the body for receiving a liquid sample; a plurality of capillary sampling channels arranged inside the body, wherein the first end of the capillary sampling channel is communicated with the loading hole, and when the liquid sample is added to the loading hole, the liquid sample will fill the capillary sampling channel through capillary action; a plurality of puncture tubes arranged on one side of the body and extending into the body, wherein the first ends of the puncture tubes located inside the body are respectively communicated with the second ends of the capillary sampling channels, and the second ends of the puncture tubes located outside the body are pointed ends.
[0112] The inner diameter of the puncture tube or the inner diameter of the contact point between the puncture tube and 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.
[0113] In some embodiments, the body is in the shape of a sheet or a plate, and the plurality of capillary sampling channels are arranged in a horizontal direction inside the body.
[0114] In some embodiments, the second end of the capillary sampling channel is connected to the first end of the puncture tube through a connecting channel, and the connecting channel is perpendicular to the plane where the multiple capillary sampling channels are located.
[0115] In some embodiments, the communicating channel is a capillary channel.
[0116] In some embodiments, the multi-channel microfluidic loading device further comprises two side walls extending from both sides of the body, forming a snap-in opening for plugging with a detection card, and when a detection card having a plurality of microcolumns and covered with a sealing film is pushed into the snap-in opening, the pointed ends of the plurality of puncture tubes pierce the sealing film covering the plurality of microcolumns.
[0117] In some embodiments, the side wall is provided with a limiting protrusion for use with a limiting groove on the detection card.
[0118] In some embodiments, a waste liquid tank connected to the loading hole is further provided inside the body. When there is too much liquid sample in the loading hole or under the action of centrifugal force, the liquid sample in the loading hole can flow into the waste liquid tank.
[0119] In some embodiments, a baffle is disposed in the waste liquid tank to limit the liquid sample from flowing back to the loading hole.
[0120] In some embodiments, the inner diameter of the capillary sampling channel is 0.5 mm, and the inner diameter of the connecting channel is 0.8 mm.
[0121] On the other hand, the present invention provides the application of the multi-channel microfluidic loading device to load samples on a blood type detection card.
[0122] It should be noted that, in this article, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, an element defined by the sentence "comprises a ..." does not exclude the existence of other identical elements in the process, method, article or device including the element.
[0123] Those skilled in the art should understand that the technical solutions described in this document may be modified, or some or all of the technical features therein may be replaced by equivalents, and these modifications or replacements should all be included in the protection scope of the present invention.
Claims
1. A multi-channel microfluidic sampling device, characterized in that: include: 1) Ontology; 2) a loading hole for receiving a liquid sample, wherein the loading port of the loading hole is located on the first surface of the body; the loading hole is a conical structure; 3) a plurality of capillary sampling channels are arranged at intervals inside the body, wherein the first ends of the capillary sampling channels are connected to the loading hole; when the liquid sample is added to the loading hole, the liquid sample fills the plurality of capillary sampling channels through capillary action; 4) a plurality of puncture tubes arranged at intervals on the first side of the body and extending into the interior of the body, wherein the first ends of the plurality of puncture tubes extending into the interior of the body are respectively connected to the second ends of the plurality of capillary sampling channels; and the second ends of the plurality of puncture tubes extending outside the body are sharp ends for puncture; The inner diameter of the puncture tube or the inner diameter of the contact point between the puncture tube and 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; Among them, a waste liquid tank connected to the loading hole is also provided inside the main body. When there is too much liquid sample in the loading hole or under the action of centrifugal force, the liquid sample in the loading hole can flow into the waste liquid tank. A baffle is provided in the waste liquid tank to limit the liquid sample from flowing back to the loading hole.
2. The multi-channel microfluidic sampling device according to claim 1, characterized in that: The body is in the shape of a sheet or a plate, and the plurality of capillary sampling channels are arranged at intervals inside the body along the length direction of the body.
3. The multi-channel microfluidic sampling device according to claim 2, characterized in that: The second end of the capillary sampling channel is communicated with the first end of the puncture tube through a connecting channel, and the connecting channel is perpendicular to the plane where the multiple capillary sampling channels are located.
4. The multi-channel microfluidic sampling device according to claim 3, characterized in that: The communicating channel is a capillary channel.
5. The multi-channel microfluidic sampling device according to claim 4, characterized in that: The inner diameter of the capillary sampling channel is 0.5 mm, and the inner diameter of the connecting channel is 0.8 mm.
6. The multi-channel microfluidic sampling device according to claim 3, characterized in that: The inner diameter of the capillary sampling channel or the connecting channel is 0.5 mm-1.2 mm.
7. The multi-channel microfluidic sampling device according to claim 1, characterized in that: 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; during the loading process, when the liquid sample overflows over the top of the sheet-like structure due to excessive liquid sample, the overflowed liquid sample enters the waste liquid tank.
8. The multi-channel microfluidic sampling device according to claim 1, characterized in that: The baffle is subjected to hydrophobic treatment; or a hydrophobic layer is provided on the baffle.
9. The multi-channel microfluidic sample loading device according to claim 1, characterized in that: The first end of the capillary sampling channel is distributed along the circumference of the loading hole.
10. The multi-channel microfluidic sampling device according to claim 1, characterized in that: The capillary sampling channel is covered with a hydrophilic film layer.
11. The multi-channel microfluidic sample loading device according to any one of claims 1 to 10, characterized in that: Also includes: Two side walls extending from two sides of the body form a card-engaging opening for plugging with a detection card; When the test card is pushed into the card-joining opening, the pointed ends of the plurality of puncture tubes pierce the sealing film covered by the opening ends of the plurality of micro-columns on the test card.
12. The multi-channel microfluidic sample loading device according to claim 11, characterized in that: The side wall is provided with a limiting card protrusion that can cooperate with the limiting card groove on the detection card; or, the detection card is provided with at least one group of limiting card grooves on both sides thereof corresponding to the limiting card protrusion on the side wall; and when the detection card is provided with two groups of limiting card grooves, one group of limiting card grooves cooperates with the limiting card protrusions so that the pointed end of the puncture tube is in a state of piercing the film material, and the other group of limiting card grooves is slightly higher. When it cooperates with the limiting card protrusions, the detection card is combined with the multi-channel microfluidic loading device, and the pointed end of the puncture tube does not pierce the film material on the detection card.
13. Use of the multi-channel microfluidic sample loading device according to any one of claims 1 to 12 in loading samples on a blood type detection card.
14. A multi-channel microfluidic sample loading assembly, characterized in that: include: The multi-channel microfluidic loading device and the detection card according to any one of claims 1 to 10, wherein the multi-channel microfluidic loading device is provided with a card connection opening that can be plugged into the detection card, and the detection card is provided with a second limit card slot and a first limit card slot on both sides; accordingly, the card connection opening includes: a sliding path for the detection card to slide, and the sliding path is provided with a limit card protrusion that can cooperate with the first limit card slot and the second limit card slot; Wherein, the detection card is installed at the second limit card slot in a manner that it can move relative to the card opening; When the limiting card protrusion is disengaged from the second limiting card slot under the action of an external force, the detection card can move along the sliding path toward the puncture tube, and when the first limiting card slot moves to the position of the limiting card protrusion and cooperates with the limiting card protrusion, the detection card and the engaging opening are engaged with the first limiting card slot, and the multiple puncture tubes on the multi-channel microfluidic loading device pierce the sealing film covered by the open ends of the multiple microcolumns on the detection card.
15. Use of the multi-channel microfluidic sample loading assembly according to claim 14 in sample loading on a blood type detection card.
Citation Information
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