HIV detection device

Abstract

The present application relates to the technical field of biological monitoring, and aims at the technical problem that secondary pollution may occur in the existing detection process, resulting in inaccurate detection results, and provides an HIV detection device, which comprises, from bottom to top, a backing layer, a collection layer, a sample processing and chromatography layer, and a result observation layer; the collection layer comprises a microneedle array layer above the backing layer and a fixed patch on the upper surface of the microneedle array layer; wherein the fixed patch in contact with the bottom of the microneedle array layer is provided with a plurality of sample flow guide channels at the corresponding positions. The present application integrates the precise quantitative collection and transmission of trace samples, flow guide and detection into a disposable patch, realizes the full-process integration of patching, blood sampling, detection and reading, and can avoid secondary pollution, so that the detection result is more accurate.

Description

Technical Field

[0001] This invention relates to the field of biological monitoring technology, and in particular to HIV detection devices and methods of use. Background Technology

[0002] AIDS, short for Acquired Immune Deficiency Syndrome, is an infectious disease caused by infection with the human immunodeficiency virus (HIV). HIV itself does not cause any disease; rather, it is the destruction of the immune system by HIV that leads to the body's inability to fight off other diseases, ultimately resulting in death.

[0003] Whole blood HIV testing has become more widespread, and there are many simple and quick test kits on the market. However, current test kits usually only include the test strip and the test strip container, while the blood collection needle, blood collection tube, and buffer solution used for the test plate are packaged separately. Secondary contamination may occur during the blood collection process, leading to inaccurate test results. Summary of the Invention

[0004] To address the aforementioned problems, this invention aims to provide an HIV testing device that integrates the precise quantitative collection and transmission, diversion and detection of trace samples into a disposable patch, achieving a fully integrated process of patch application, blood collection, detection and reading, thus avoiding secondary contamination and making the test results more accurate.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The HIV testing device includes, from bottom to top, a backing layer, a collection layer, a sample processing and chromatography layer, and a result observation layer; The acquisition layer includes a microneedle array layer located above the backing layer and a fixing patch located on the upper surface of the microneedle array layer; Among them, multiple sample flow channels are provided at the corresponding positions of the fixing patch that contacts the bottom of the microneedle array layer.

[0006] Preferably, the microneedle array layer includes multiple solid microneedles, and the spacing between two adjacent solid microneedles is 200-500 μm; Each solid microneedle has its tip pointing away from the end of the adhesive patch.

[0007] Preferably, the length of each solid microneedle is 500~1000μm.

[0008] Preferably, multiple solid microneedles form a regular hexagonal honeycomb array structure with an array density of 200~500 needles / cm².

[0009] Preferably, each solid microneedle is a multi-stage frustum, consisting of a pointed cone section, a transition cone section, and a cylindrical base section from the tip to the root.

[0010] Preferably, each solid microneedle has a spiral liquid guiding groove on its surface, and the width of the spiral liquid guiding groove is 0.05-0.1mm.

[0011] Preferably, the inlet width of each sample flow channel is greater than the outlet width.

[0012] Preferably, the inlet width of each sample flow channel is 1.5-3mm, the outlet width is 1-2mm, and the depth is 0.1-0.3mm.

[0013] Preferably, the surface of each solid microneedle is coated with a hydrophilic hyaluronic acid coating.

[0014] Compared with the prior art, the beneficial effects of the present invention are: This application integrates the precise quantitative collection and transmission, diversion and detection of trace samples into a disposable patch, realizing the whole process of patching, blood collection, detection and reading, which can avoid secondary pollution and make the test results more accurate.

[0015] Specifically, in the precise quantitative collection and transmission of trace samples, this application achieves efficient sample induction and exudation by synergistically optimizing the length of the solid microneedles, the hexagonal honeycomb array structure, and their density and spacing. This allows the solid microneedles to penetrate only the epidermis and superficial dermis, ensuring painlessness and safety while achieving efficient sample induction and exudation. The densely packed honeycomb structure distributes stress evenly, ensuring consistency in puncture depth and maximizing the number of solid microneedles per unit area. The mutual restraint between the arrays effectively enhances the mechanical strength of the solid microneedles, making them less prone to bending or breakage.

[0016] In terms of flow guidance and detection, this application combines a multi-stage frustum solid microneedle with a spiral liquid-guiding groove on the surface of the solid microneedle to achieve rapid liquid guidance through capillary action. A sample flow channel directly connecting sample processing and the chromatography layer is designed in the fixing patch at the bottom of the solid microneedle. The inlet width of this sample flow channel is greater than the outlet width, which can rapidly capture and collect the trace sample guided by the solid microneedle through the hydrodynamic convergence effect, preventing lateral diffusion and evaporation loss, ensuring uniform diffusion of the sample in the detection area, and enabling the sample to enter the detection system immediately after collection. This maximizes the utilization rate, transmission efficiency, and detection stability of trace samples, laying a key foundation for achieving rapid, accurate, and highly repeatable HIV detection. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the HIV detection device of the present invention.

[0018] Figure 2 This is a schematic diagram of the regular hexagonal honeycomb array structure composed of multiple solid microneedles of the present invention.

[0019] Figure 3 This is a schematic diagram of the solid microneedle of the present invention.

[0020] Figure 4 This is a flowchart of the HIV detection device of the present invention.

[0021] The structure includes: 1. Backing layer, 2. Microneedle array layer, 3. Fixing patch, 4. Sample processing and chromatography layer, 5. Result observation layer, 6. Quality control line, 7. Test line, 8. Cylindrical base section, 9. Transition cone section, 10. Tip cone section, 11. Spiral liquid guide groove, 12. Solid microneedle. Detailed Implementation

[0022] To enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and embodiments. Example 1

[0023] Please see Figure 1-4 The HIV testing device of this application is based on the principle of colloidal gold immunochromatography, which integrates microneedle blood collection, sample chromatography and result color development into a disposable patch, realizing the whole process of patching, blood collection, testing and reading. Patients can determine whether they are HIV antibody positive by visually observing the color development results within a few minutes after patching.

[0024] The HIV testing device of this application includes, from bottom to top, a backing layer 1, a collection layer, a sample processing and chromatography layer 4, and a result observation layer 5.

[0025] Specifically, backing layer 1 is made of medical breathable and waterproof non-woven fabric, which serves to fix and protect the skin. The edges are designed with medical pressure-sensitive adhesive to ensure close contact with the skin during application.

[0026] The collection layer includes a microneedle array layer 2 located above the backing layer 1 and a fixing patch 3 located on the upper surface of the microneedle array layer 2; and the edge of the fixing patch 3 is designed as an adhesive layer, which can be tightly attached to the backing layer 2. The microneedle array layer 2 includes multiple solid microneedles 12, with a spacing of 200-500 μm between adjacent solid microneedles 12. The tip of each solid microneedle 12 points away from the fixed patch 3; the length of each solid microneedle 12 is 500-1000 μm. The multiple solid microneedles form a regular hexagonal honeycomb array structure with an array density of 200-500 needles / cm².

[0027] These solid microneedles 12 are all made of biodegradable polymers (such as polylactic acid PLA). The microneedle array layer 2 penetrates the epidermal layer of the skin to collect blood (containing HIV antibodies) without causing obvious pain. The bottom of the microneedle array layer 2 is connected to the sample flow channel, and the collected sample can directly enter the sample processing and chromatography layer 4.

[0028] Specifically, the honeycomb-like dense arrangement ensures uniform stress distribution, consistent puncture depth, and maximizes the number of microneedles per unit area. The array mutually restrains each other, making the solid microneedles less prone to bending and breakage. The 500-1000μm microneedle length allows for precise control of blood collection depth, penetrating only the epidermis and superficial dermis. This avoids pain nerves and deep blood vessels, ensuring painlessness and safety while effectively inducing sufficient interstitial and tissue fluid exudation. The array density of 200-500 needles / cm², combined with a spacing of 200-500μm, not only enables simultaneous multi-point blood collection within a limited area to improve collection efficiency but also avoids excessive skin damage or sample spillage through appropriate spacing, thus ensuring the stability of the blood volume collected per session. Preferably, the microneedle length is 1000μm, the array density is 500 needles / cm², and the spacing between adjacent microneedles is 500μm. Meanwhile, the sample guide channel adopts a hydrophilic coating and directly connects to the sample processing and chromatography layer 4, enabling the sample to enter the detection system immediately after collection. The entire process is free of exposure, transfer, and residue. This device truly achieves controllable and quantitative one-pattern sampling and testing without the need for external buffer solutions, pipettes, and blood collection tubes, greatly improving the convenience, accuracy, and repeatability of home self-testing.

[0029] Preferably, each solid microneedle 12 is a multi-stage frustum structure, comprising a pointed cone section 10, a transition cone section 9, and a cylindrical base section 8 sequentially from the tip to the root. Furthermore, each solid microneedle 12 has a spiral liquid-guiding groove 11 on its surface, the width of which is 0.05-0.1 mm, preferably 0.1 mm. The core effect of this application's combination of the multi-stage frustum structure and the 0.1 mm spiral liquid-guiding groove 11 is to utilize capillary force to achieve rapid liquid guidance of trace amounts of HIV samples. The multi-stage frustum transition from the tip to the root guides the sample to uniformly fill the spiral liquid-guiding groove 11 through a gradually increasing cross-section, avoiding air bubble residue; while the 0.1 mm narrow groove design ensures sufficient capillary driving force and limits the liquid flow rate, allowing the sample to diffuse slowly and stably in the detection area, reducing sample waste and improving the repeatability and accuracy of the detection, especially suitable for the rapid sample loading requirements of trace amounts.

[0030] In addition, each solid microneedle 12 is coated with a hydrophilic hyaluronic acid coating. It should be noted that the hydrophilic hyaluronic acid coating is a hydrophilic modified coating with hyaluronic acid as the main functional component, fixed to the surface of materials (such as medical devices, implants, or dressings) through physical or chemical means. Its composition and ratio are existing technologies, and this application has not improved upon them; therefore, they will not be elaborated further here. This coating significantly enhances the hydrophilicity of the microneedle surface. Since interstitial fluid and tissue fluid are inherently aqueous systems, the strong hydrophilic properties of hyaluronic acid can significantly reduce the contact angle of the liquid on the microneedle surface, thereby strengthening the capillary driving force within the spiral fluid-conducting groove 11. This improved wettability allows micro-volume tissue fluid to more quickly and uniformly wet and fill the fluid-conducting groove, effectively avoiding air bubble residue or liquid adhesion caused by hydrophobicity, ensuring the continuity and stability of the fluid-conducting process.

[0031] Secondly, hyaluronic acid, a naturally occurring component of the skin, possesses excellent biocompatibility and lubricity. At the moment the microneedle pierces the skin, this coating not only lubricates and reduces resistance, decreasing mechanical friction during puncture to alleviate pain, but also promotes instantaneous hydration of skin tissue, helping to open transcellular pathways and thereby inducing a greater amount of interstitial fluid exudation, thus improving blood collection efficiency from the source.

[0032] Finally, the coating forms a perfect, seamless connection with the funnel-shaped, gradually shrinking drainage channel on the fixation patch. When the hyaluronic acid-rich microneedles are withdrawn or in place, the hydrophilic coating on their surface guides the exudated tissue fluid to rapidly converge towards the fixation patch 3 at the bottom, preventing lateral diffusion and evaporation loss of the sample at the bottom of the solid microneedles 12 or the interface of the fixation patch 3. This deep synergy between material and structure ensures efficient sample capture and non-destructive transport, further solidifying the accuracy and repeatability of HIV testing results.

[0033] More specifically, the base of the microneedle array layer 2 is fixedly connected to the fixing patch 3; the fixing patch 3 at the bottom of the solid microneedle 12 has a sample flow channel, with one solid microneedle 12 corresponding to one sample flow channel. The solid microneedle 12 punctures the skin epidermis to form tiny exudate channels. Tissue fluid or trace amounts of blood exudated from the skin collect at the bottom of the solid microneedle 12 and, under capillary action, directly enter the sample processing and chromatography layer 4 through the sample flow channel, achieving stable and quantitative sample delivery without the need for needle aspiration.

[0034] The sample diversion channels are specifically located in the area where the fixing patch 3 adheres to the bottom of the microneedle array layer 2. Multiple sample diversion channels form a connected channel array covering the entire microneedle array layer 2. Each sample diversion channel is a funnel-shaped, gradually contracting channel with an inlet width greater than its outlet width. The inlet width of each sample diversion channel is 1.5-3 mm, the outlet width is 1-2 mm, and the depth is 0.1-0.3 mm. One end of each sample diversion channel corresponds to the microneedle blood collection area, and the other end connects to the sample processing and chromatography layer 4, achieving diversion without exposure of exudate and without dead space.

[0035] Specifically, this application achieves efficient collection and directional transport of micro-collected samples by setting a sample guide channel with the aforementioned specific structure on the fixing patch in contact with the bottom of the microneedle array layer. The funnel-shaped, gradually contracting channel design of the sample guide channel creates a natural convergence effect in terms of hydrodynamics, enabling the rapid capture of trace amounts of tissue fluid or blood extracted after the microneedles pierce the skin from the wider inlet end and concentrating it towards the narrower end. This structure not only significantly improves sample collection efficiency but also effectively prevents lateral diffusion and loss of liquid during transport, ensuring the integrity of the sample entering the subsequent detection layer.

[0036] Preferably, this application precisely sets the inlet width of the sample flow channel to 2.0 mm, the outlet width to 1.0 mm, and the depth to 0.2 mm. The width ratio of the inlet to the outlet creates an ideal funnel effect: the wider inlet (2.0 mm) provides ample lateral space for the micro-volume tissue fluid collected by the microneedle, effectively preventing sample overflow or blockage due to an excessively narrow channel; while the gradually narrowing outlet (1.0 mm) forms a smooth transition with the inlet, avoiding excessive spreading of the liquid during transport. This wide-inlet, narrow-outlet structure not only utilizes fluid dynamics principles to naturally collect the sample, reducing exposed surface area and the risk of evaporation, but also ensures that the sample can be concentrated and directed towards the outlet. Combined with the specific depth of 0.2 mm, this design maintains appropriate capillary driving force while ensuring smooth fluid entry, assisting the sample to spontaneously and rapidly flow downstream to sample processing and chromatography layer 4. Overall, this size combination, through the coordination of the inlet and outlet, perfectly balances sample capacity, transmission flow rate, and anti-evaporation requirements, maximizing sample utilization and laying a key foundation for achieving rapid and accurate HIV detection, while further ensuring the smoothness and stability of sample transmission.

[0037] Sample processing and chromatography layer 4 includes a sample pad, a colloidal gold pad, and an NC membrane; Among them, the sample pad is located next to the sample flow channel outlet in the fixation patch 3. It contains absorbent fibers, which can quickly absorb the interstitial fluid collected by the solid microneedles 12 and perform preliminary filtration and slow release of the sample; a small amount of stabilizer is pre-embedded to avoid antibody inactivation.

[0038] Colloidal gold pad: Located above the sample pad, it contains HIV recombinant antigen (type 1+2) labeled with colloidal gold. When the sample solution flows through this area, if it contains HIV antibodies, it will bind with the colloidal gold-labeled antigen to form an antibody-colloidal gold antigen complex.

[0039] NC membrane (nitrocellulose membrane): Covering the colloidal gold pad, it serves as a reaction carrier. Two detection lines are drawn on its upper surface: test line 7 (T line) and control line 6 (C line). Test line 7 (T line): Coated with HIV recombinant antigen, it turns red upon binding to the antibody-colloidal gold antigen complex due to the aggregation of colloidal gold. It should be noted that coating means: stably immobilizing the antigen or antibody on the surface of the test strip material for specific binding and color development.

[0040] Control line 6 (C line): Coated with a specific antibody corresponding to the gold-labeled antigen. Regardless of whether the sample contains HIV antibodies, it will bind to the colloidal gold-labeled antigen and produce a color change, which is used to verify the effectiveness of the test.

[0041] The result observation layer 5 includes an absorbent filter paper layer located above the NC membrane, and a transparent PET window located on the upper surface of the absorbent filter paper layer, corresponding to the positions of the test line 7 and the quality control line 6, to facilitate visual reading of the results.

[0042] It should be noted that the absorbent filter paper layer can provide the driving force for sample chromatography through capillary action, ensuring that the liquid flows through the detection line at a uniform speed.

[0043] Through the coordination of the aforementioned structures, this device enables precise control of the interstitial fluid collection volume from the source. Specifically, the length, density, and spacing of the microneedle array are optimized to achieve multi-point simultaneous blood collection within a limited skin area, ensuring that the volume of interstitial fluid collected in a single session remains stable at approximately 50 μL. This precise quantitative blood collection capability, combined with the matching absorbency and conduction rate of the sample pad, effectively avoids the pre- or post-traumatic banding phenomena caused by excessively large or small sample volumes in traditional blood collection methods, providing a reliable sample basis for the accuracy of subsequent test results.

[0044] To ensure the complete and efficient utilization of the 50μL sample by the detection system, the device features targeted designs in the connection between the microneedles and the detection layer, as well as reagent integration. On one hand, a sample flow channel is created within the fixing patch at the bottom of the microneedle array layer. One end of this channel connects to the blood collection area, and the other end directly connects to the chromatography sample pad. A hydrophilic coating completely eliminates dead space in sample transport, ensuring the sample enters the detection membrane strip without loss. On the other hand, the required 10μL buffer solution (divided evenly into 5 portions of 2μL each) is pre-embedded in a dry state and then vacuum-dried and fixed onto the sample pad. When the 50μL sample collected by the solid microneedles 12 flows through, the pre-embedded buffer solution automatically dissolves and releases, eliminating the cumbersome step of adding external buffer solution and achieving perfect sample-reagent matching and fully automated reaction. Example 2

[0045] The usage process of the HIV testing device in this application is as follows: 1. Application of the patch and quantitative blood collection After the patient cleans smooth skin areas such as the inner arm, the backing layer 1 is removed, and the entire device is fitted onto the skin surface. Moderate pressure is applied to allow the microneedle array layer 2 to penetrate the epidermis and superficial dermis. Under pressure, solid microneedles 12, with a length of 500-1000 μm, penetrate the skin to form micropores, inducing the exudation of interstitial fluid. At this time, the hydrophilic hyaluronic acid coating on the surface of the solid microneedles 12 is rapidly wetted, and in conjunction with the spiral fluid-guiding grooves 11 on the surface of the solid microneedles 12, capillary action guides the exudate from the tip of the solid microneedles 12 towards its root. Due to the optimized hexagonal honeycomb array structure and its synergistic density and spacing, the solid microneedles 12 penetrate only the epidermis and superficial dermis, achieving efficient sample induction and exudation while ensuring painlessness and safety. The densely packed honeycomb structure ensures uniform stress distribution, guaranteeing consistent puncture depth and maximizing the number of solid microneedles per unit area. The mutual restraint between the arrays effectively enhances the mechanical strength of the solid microneedles, making them less prone to bending or breakage. This process allows for precise control of puncture depth and blood collection volume, achieving a quantitative blood collection of approximately 50 μL, ensuring a stable single-sample volume to meet subsequent testing requirements.

[0046] 2. Lossless transmission and sample import The collected samples, driven by capillary force, converge at the base of the solid microneedle 12 and enter the pre-set sample flow channel within the fixing patch 3. This flow channel features a funnel-shaped, gradually contracting design with an inlet width of 2.0 mm and an outlet narrowness of 1.0 mm, which efficiently captures the sample and prevents lateral diffusion. Within this channel, the sample is rapidly concentrated and guided to the outlet, directly and non-destructively injected into the sample pad of the sample processing and chromatography layer 4. The entire process requires no manual transfer, eliminating the risk of sample exposure and secondary contamination.

[0047] 3. Automated Chromatographic Reaction After the sample enters the sample pad, chromatography begins thanks to the capillary force provided by the absorbent filter paper layer. The pre-embedded buffer solution (dry state) in the sample pad dissolves upon contact with the liquid, filtering and releasing the sample. If the sample contains HIV antibodies, they will bind to the colloidal gold-labeled antigen released from the colloidal gold pad, forming an antibody-colloidal gold antigen complex. As this complex flows through the NC membrane, in positive samples, the complex will be specifically captured and aggregated for color development by the HIV recombinant antigen coated on test line 7 (T line); regardless of whether the sample is positive or negative, excess colloidal gold-labeled antigen will continue to flow and be captured and developed for color development by control line 6 (C line) to verify the effectiveness of the reaction system.

[0048] 4. Result Interpretation Five to ten minutes after application, once the chromatography process is complete, the patient can directly observe the color development through the transparent PET window of the results observation layer 5: if both the T and C lines are red, the result is positive; if only the C line is red, the result is negative; if the C line is not colored, the test process is invalid and needs to be repeated. This process achieves a fully integrated operation of one-time application and immediate testing, significantly improving the convenience of testing and the accuracy of results.

[0049] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. An HIV testing device, comprising, from bottom to top, a backing layer (1), a collection layer, a sample processing and chromatography layer (4), and a result observation layer (5); characterized in that, The acquisition layer includes a microneedle array layer (2) located above the backing layer (1) and a fixing patch (3) located on the upper surface of the microneedle array layer (2). Among them, the corresponding position of the fixing patch (3) that is in contact with the bottom of the microneedle array layer (2) is provided with multiple sample guide channels.

2. The HIV detection device according to claim 1, characterized in that, The microneedle array layer (2) includes multiple solid microneedles (12), and the spacing between two adjacent solid microneedles (12) is 200-500μm; In this case, the tip of each solid microneedle (12) is directed toward the end away from the fixing patch (3).

3. The HIV detection device according to claim 2, characterized in that, Each solid microneedle (12) has a length of 500~1000μm.

4. The HIV detection device according to claim 2, characterized in that, Multiple solid microneedles (12) form a regular hexagonal honeycomb array structure with an array density of 200~500 needles / cm².

5. The HIV detection device according to claim 3, characterized in that, Each solid microneedle (12) is a multi-stage frustum, consisting of a pointed cone section (10), a transition cone section (9), and a cylindrical base section (8) from the tip to the root.

6. The HIV detection device according to claim 3, characterized in that, Each solid microneedle (12) has a spiral liquid guiding groove (11) on its surface, and the width of the spiral liquid guiding groove (11) is 0.05-0.1mm.

7. The HIV detection device according to claim 1, characterized in that, The inlet width of each sample flow channel is greater than the outlet width.

8. The HIV detection device according to claim 7, characterized in that, The inlet width of each sample flow channel is 1.5-3mm, the outlet width is 1-2mm, and the depth is 0.1-0.3mm.

9. The HIV detection device according to claim 3, characterized in that, Each solid microneedle (12) is coated with a hydrophilic hyaluronic acid coating.

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