Rapid diagnosis device for bacteria on wound surface
By combining hollow microneedle and microfluidic chip devices, the problem of interference factors in wound bacteria detection is solved, and efficient and accurate bacteria detection is achieved, reducing costs and simplifying operations.
Patent Information
- Application Number
- CN202421154591.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-05-24
- Publication Date
- 2025-04-25
- Estimated Expiration
- 2034-05-24
AI Technical Summary
The prior art is difficult to effectively solve the interfering factors in wound bacteria detection, such as scabs and biofilms, resulting in low detection efficiency and accuracy.
A device combining hollow microneedle and microfluidic chip is used to automatically collect wound tissue fluid through hollow microneedle, and bacterial detection is performed using the enzyme reaction zone and color development zone in the microfluidic chip.
It significantly improves the efficiency and accuracy of wound bacteria detection, reduces the amount of tissue fluid, reduces costs, and enables rapid testing without the help of medical staff.
Smart Images
Figure CN222787772U_ABST
Abstract
Description
Technical Field
[0001] The utility model belongs to the technical field of biological detection, in particular to a device for rapid diagnosis of wound bacteria. Background Art
[0002] Bacterial infection can cause dramatic changes in the microenvironment around it, including an increase in the amount of enzymes secreted by bacteria (such as β-lactamase) and a decrease in the pH of the microenvironment caused by acidic metabolites. The scabs and biofilms on the wound surface often interfere with the detection and diagnosis of internal bacteria.
[0003] Therefore, there is an urgent need to quickly diagnose and identify bacteria on the wound surface and guide the subsequent selection of antibiotics for targeted treatment. Utility Model Content
[0004] The purpose of the utility model is to overcome the shortcomings of the prior art and provide a wound bacteria rapid diagnosis device which is low in cost, easy to operate and can significantly improve the detection efficiency and accuracy.
[0005] The utility model solves the technical problem by adopting the following technical solutions:
[0006] A wound bacteria rapid diagnosis device, comprising:
[0007] A hollow microneedle, a microneedle base, an isolation membrane, a microfluidic chip and a backing, wherein the hollow microneedle is a hollow setting with upper and lower openings, and the upper end is opened at the microneedle base, the microneedle base is set in a circular groove, and the bottom plate of the microneedle base is provided with a plurality of microholes, each microhole corresponding to a hollow microneedle, and an isolation membrane and a microfluidic chip are coaxially embedded in the bottom plate of the microneedle base from bottom to top, and a backing is coaxially covered on the top of the microfluidic chip;
[0008] The microfluidic chip has a liquid inlet at the center, and an annular groove at the outer edge of the microfluidic chip. A plurality of microfluidic channels are arranged in the microfluidic chip between the liquid inlet and the annular groove. An enzyme reaction area and a color development area are arranged in series on the microfluidic channel, and the enzyme reaction area is located at one end close to the liquid inlet.
[0009] Moreover, each hollow microneedle is composed of a composite of a hydrophobic polymer material and nanoparticles, wherein the hydrophobic polymer material includes but is not limited to polycaprolactone and polylactic acid.
[0010] Moreover, the microfluidic chip is made of highly elastic materials including but not limited to polydimethylsiloxane and polyurethane.
[0011] Furthermore, the isolation membrane is an asymmetric sulfoxide membrane.
[0012] Moreover, the isolation membrane is a detachable isolation membrane.
[0013] Moreover, the bottom plate area of the microneedle base is larger than the areas of the isolation membrane and the microfluidic chip, and the edge height of the microneedle base is equivalent to the height of the isolation membrane and the microfluidic chip.
[0014] Moreover, the microneedle base is provided with an air outlet, and the air outlet and the annular groove of the microfluidic chip are located at the same height.
[0015] Moreover, the backing is a transparent film material, and the area of the backing is larger than the area of the microneedle base. The area exceeding the microneedle base is the adhesion area, and the area coaxial and equal to the microneedle base is the printing instruction area. The corresponding color display position of the printing instruction area is marked with printed instructions.
[0016] Moreover, the thickness of the annular groove is smaller than the thickness of the isolation membrane, the thickness of the isolation membrane is smaller than the thickness of the backing, the thickness of the backing is smaller than the thickness of the microneedle base, and the thickness of the microneedle base is smaller than the thickness of the microfluidic chip.
[0017] Moreover, the color development area is located at the end of the microfluidic channel, and the liquid inlet is connected to the microfluidic channel, the microfluidic channel is connected to the annular groove, and the annular groove is connected to the air outlet.
[0018] The advantages and positive effects of the utility model are:
[0019] The utility model combines the dual advantages of hollow microneedles and microfluidic systems, and can automatically collect, separate, and detect functions by finger operation. The whole device is made of low-cost materials such as polymers, which is cheaper than traditional medical equipment and can be used and discarded. At the same time, the fluid collected by the hollow microneedle is directly introduced into the microfluidic chip for analysis and detection, which significantly reduces the amount of tissue fluid and improves detection efficiency and accuracy.
[0020] The utility model only requires relatively low concentrations of biomarkers, has low reagent loss, high sensitivity and good accuracy, so that users can simply, quickly and effectively collect their own wound tissue fluid without the help of medical personnel. During the sampling process, subcutaneous body fluid is extracted or entered in a minimally invasive and painless manner. It can be used for subcutaneous sampling and analysis in the fields of vital sign detection, tumor markers, biomacromolecule detection, etc. It can also be used in minimally invasive personalized medical equipment, and as a wearable microsensor to achieve real-time monitoring, and has a wide range of applications. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 It is a side view of the utility model.
[0022] Figure 2 It is a top view of the microneedle base of the utility model.
[0023] Figure 3 It is a top view of the microfluidic chip of the present invention.
[0024] Figure 4 It is a schematic diagram of the backing of the utility model.
[0025] Reference numerals
[0026] 1-microneedle base, 2-backing, 3-microfluidic chip, 4-isolation membrane, 5-ring groove, 6-air outlet, 7-hollow microneedle, 8-micropore, 9-enzyme reaction area, 10-liquid inlet, 11-microfluidic channel, 12-color development area, 13-pipette, 14-printing instruction area, 15-adhesion area. DETAILED DESCRIPTION
[0027] The present invention will be further described in detail below with reference to the accompanying drawings and through specific embodiments. The following embodiments are merely descriptive and not restrictive, and the protection scope of the present invention cannot be limited thereto.
[0028] A wound bacteria rapid diagnosis device, comprising:
[0029] A hollow microneedle 7, a microneedle base 1, an isolation membrane 4, a microfluidic chip 3 and a backing 2, wherein the hollow microneedle 7 is a hollow setting with upper and lower openings, and the upper end is opened at the microneedle base 1, and the microneedle base 1 is set in a circular groove. The bottom plate of the microneedle base 1 is provided with a plurality of micropores 8, and each micropore 8 is connected to a corresponding hollow microneedle 7. The isolation membrane 4 and the microfluidic chip 3 are coaxially embedded in the upper part of the bottom plate in the microneedle base 1 from bottom to top, and a backing 2 for printing instructions is coaxially covered on the upper part of the microfluidic chip 3;
[0030] A liquid inlet 10 is provided at the center of the microfluidic chip 3, and an annular groove 5 is formed on the outer edge of the microfluidic chip 3. A plurality of microfluidic channels 11 are arranged in the microfluidic chip 3 between the liquid inlet 10 and the annular groove 5, and an enzyme reaction area 9 and a color development area 12 are arranged in series on the microfluidic channel 11, and the enzyme reaction area 9 is located at one end close to the liquid inlet 10.
[0031] Each hollow microneedle 7 is composed of a composite of a hydrophobic polymer material and nanoparticles, wherein the hydrophobic polymer material includes but is not limited to polycaprolactone and polylactic acid, which is used to enhance the rigidity of the material, and a hollow structure penetrating the microneedle is formed inside the microneedle by molding, soft etching, microcontact printing, etc.
[0032] The microfluidic chip 3 is made of highly elastic material including but not limited to polydimethylsiloxane and polyurethane, and is made by laser, etching, micro-molding, etc.
[0033] The isolation membrane 4 is an asymmetric sulfoxide membrane, which is used to isolate tissue fragments and blood cells in the wound tissue fluid.
[0034] The isolation membrane 4 is a detachable isolation membrane. According to the needs of the user, the isolation membrane can be removed when performing bacterial intracellular enzyme detection, and can be installed and used when performing bacterial extracellular enzyme and other small molecule detection.
[0035] The bottom plate area of the microneedle base 1 is larger than the areas of the isolation membrane 4 and the microfluidic chip 3 , and the edge height of the microneedle base 1 is equivalent to the height of the isolation membrane 4 and the microfluidic chip 3 .
[0036] The microneedle base 1 is provided with an air outlet 6, which is located at the same height as the annular groove 5 of the microfluidic chip 3, and is used to cooperate with the matching plastic straw 13 to enhance the negative pressure attraction, thereby increasing the extraction rate of wound tissue fluid and directly sucking the tissue fluid out into the microfluidic channel 11.
[0037] The backing 2 is a transparent film material, and the area of the backing 2 is larger than the area of the microneedle base 1. The area exceeding the microneedle base 1 is the adhesion area 15, and the area coaxial and equal to the microneedle base 1 is the printed description area 14. The corresponding color display position of the printed description area 14 is marked with printed instructions, which allows users to quickly identify bacteria intuitively.
[0038] The thickness of the annular groove 5 is smaller than that of the isolation membrane 4 , the thickness of the isolation membrane 4 is smaller than that of the backing 2 , the thickness of the backing 2 is smaller than that of the microneedle base 1 , and the thickness of the microneedle base 1 is smaller than that of the microfluidic chip 3 .
[0039] The color development area is located at the end of the microfluidic channel, and the liquid inlet is connected to the microfluidic channel, the microfluidic channel is connected to the annular groove, and the annular groove is connected to the air outlet.
[0040] Reaction principle:
[0041] The utility model combines hollow microneedles with microfluidic technology. The hollow microneedles are made of hydrophobic polymer materials such as polycaprolactone, polylactic acid, etc. and nanoparticle composite reinforcement materials to enhance material rigidity. A hollow structure penetrating the microneedle is formed inside the microneedle by molding, soft etching, microcontact printing, etc. The microfluidic channel is made of highly elastic materials including but not limited to polydimethylsiloxane and polyurethane, and is made by laser, etching, micromolding, etc.
[0042] The device uses finger pressure to insert hollow microneedles into the wound and deform the highly elastic microfluidic chip. The microfluidic channel is compressed. During the deformation recovery process, the hollow channel of the hollow microneedle extracts the tissue fluid inside the wound through negative pressure and capillary action. Tissue fragments and blood cells are separated from the tissue fluid through the isolation membrane through the asymmetric sulfoxide membrane molecular exclusion effect. The remaining tissue fluid enters the enzyme reaction area through the liquid inlet hole of the microfluidic chip, undergoes an exclusive chemical reaction with the specific enzyme substrate in this area, and then flows into the color development area for color development, and the specific enzyme in the bacteria is detected by colorimetry.
[0043] The enzyme reaction area can be replaced by gold nanoparticles labeled with enzyme substrates. The relevant enzymes in the bacteria react with the gold nanoparticles labeled with enzyme substrates. The stability of Au-NPS decreases and aggregation occurs. The particles gradually become larger and the color gradually deepens, from yellow to wine red, purple red, brown, and black, showing the color change of gold nanoparticles related to the particle size. Qualitative analysis can be performed by visual inspection or quantitative analysis can be performed by directly reading the light absorption.
[0044] Embodiment 1:
[0045] The hollow microneedle tip is 0.5-1.0mm high, the outer diameter is 0.3-0.6mm, the hollow hole diameter is 0.05-0.1mm, a hole of 0.1-0.25mm is opened on the 0.5mm thick microneedle base, the microneedle base is concave, the outer height is 1.6-3.1mm, the outer diameter is 30mm, the concave edge thickness is 1-2mm, the concave height is 1.1-2.6mm, the isolation membrane diameter is 26-28mm, the thickness is 0.02-0.04mm, the microfluidic chip diameter is 26-28mm, the height is 1-2.5mm, A liquid inlet with a diameter of 0.1 to 0.25 mm is provided in the middle of the fluidic chip, which is connected to multiple microfluidic channels with a diameter of 0.05 to 0.1 mm and a length of 13 to 14 mm. A 2 mm enzyme reaction area is provided 2 mm away from the liquid inlet, and a 3 mm color development area is provided 2 mm away from the end. The microfluidic chip is provided with a 0.02 mm wide annular groove communicating with the microfluidic channel at the horizontal layer at the end. The backing has a diameter of 35 mm and a thickness of 0.1 to 0.2 mm. The central diameter of 30 mm is a printed description area, and the area greater than 30 cm is a glue coating adhesion area.
[0046] Glycyl-prolyl-arginyl-4-methoxy-β-naphthylamine is added to the enzyme reaction zone 1, and cinnamaldehyde is added to the color development zone 1. When encountering pathogenic Staphylococcus aureus that produces coagulase, it turns purple-red. The printed instruction area has a gray coil at the corresponding color development zone position, with a number mark "1" inside.
[0047] Nitrocefin is added to the enzyme reaction zone 2, and bromothymol blue is added to the color development zone 2. When encountering β-lactamase-producing resistant bacteria, it will turn red. The printed instruction area has a gray coil with a number "2" in it at the corresponding color development zone position.
[0048] Tryptophan is added to the enzyme reaction zone 3, and p-dimethylaminobenzaldehyde is added to the color development zone 2. When encountering tryptophanase-producing Escherichia coli, Proteus and Vibrio cholerae, rose red color appears. There is a gray coil with a number "3" in the printed instruction area at the corresponding color development zone position.
[0049] Cytochrome C is added to the enzyme reaction zone 4, and p-phenylenediamine is added to the color development zone 4. When encountering Pseudomonas aeruginosa that produces cytochrome oxidase, it will turn pink or purple. The printed instruction area has a gray coil at the corresponding color development zone position, with the number "4" inside.
[0050] Phenylalanine is added to the enzyme reaction zone 5, and ferric chloride is added to the color development zone 5. When it encounters Proteus that produces phenylalanine deaminase, it will turn green. The printed instruction area has a gray coil with a number "5" inside at the corresponding color development zone position.
[0051] Hyaluronic acid is added to the enzyme reaction zone 6, and Alcian blue is added to the color development zone 6. When encountering hemolytic streptococci and Staphylococcus aureus that produce hyaluronidase, blue color will appear. There is a gray coil with a number "6" in the printed instruction area at the corresponding color development zone position.
[0052] According to the color of the printed mark area, refer to the instructions for use provided by the product to determine the bacterial infection of the wound.
[0053] The bacterial detection type, enzyme reaction substrate and color developing agent are not limited to the above examples and can be adjusted as needed.
[0054] Although the embodiments and drawings of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments and drawings.
Claims
1. A rapid wound bacteria diagnosis device, characterized by: include: A hollow microneedle, a microneedle base, an isolation membrane, a microfluidic chip and a backing, wherein the hollow microneedle is a hollow setting with upper and lower openings, and the upper end is opened at the microneedle base, the microneedle base is set in a circular groove, and the bottom plate of the microneedle base is provided with a plurality of microholes, each microhole corresponding to a hollow microneedle, and an isolation membrane and a microfluidic chip are coaxially embedded in the bottom plate of the microneedle base from bottom to top, and a backing is coaxially covered on the top of the microfluidic chip; The microfluidic chip has a liquid inlet at the center, and an annular groove at the outer edge of the microfluidic chip. A plurality of microfluidic channels are arranged in the microfluidic chip between the liquid inlet and the annular groove. An enzyme reaction area and a color development area are arranged in series on the microfluidic channel, and the enzyme reaction area is located at one end close to the liquid inlet.
2. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: Each hollow microneedle is composed of a composite of a hydrophobic polymer material and nanoparticles, wherein the hydrophobic polymer material includes but is not limited to polycaprolactone and polylactic acid.
3. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: The microfluidic chip is made of highly elastic material including but not limited to polydimethylsiloxane and polyurethane.
4. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: The isolation membrane is an asymmetric sulfoxide membrane.
5. A wound bacteria rapid diagnosis device according to claim 4, characterized in that: The isolation membrane is a detachable isolation membrane.
6. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: The bottom plate area of the microneedle base is larger than the area of the isolation membrane and the microfluidic chip, and the edge height of the microneedle base is equivalent to the height of the isolation membrane and the microfluidic chip.
7. A wound bacteria rapid diagnosis device according to claim 6, characterized in that: The microneedle base is provided with an air outlet, and the air outlet and the annular groove of the microfluidic chip are located at the same height.
8. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: The backing is a transparent film material, and the area of the backing is larger than the area of the microneedle base. The area exceeding the microneedle base is the adhesion area, and the area coaxial and equal to the microneedle base is the printing description area. The corresponding color display position of the printing description area is marked with printed instructions.
9. A wound bacteria rapid diagnosis device according to claim 1, characterized in that: The thickness of the annular groove is smaller than the thickness of the isolation membrane, the thickness of the isolation membrane is smaller than the thickness of the backing, the thickness of the backing is smaller than the thickness of the microneedle base, and the thickness of the microneedle base is smaller than the thickness of the microfluidic chip.
10. A wound bacteria rapid diagnosis device according to claim 1 or 7, characterized in that: The color development area is located at the end of the microfluidic channel, and the liquid inlet is connected to the microfluidic channel, the microfluidic channel is connected to the annular groove, and the annular groove is connected to the air outlet.