HPV-DNA nano sensing patch device for cervix uteri self-inspection

Abstract

The invention discloses a cervical self-test HPV-DNA nano sensing patch device, and relates to the technical field of medical equipment, and the technical scheme is characterized in that the cervical self-test HPV-DNA nano sensing patch device comprises a patch structure and a detection module; the patch structure comprises a flexible substrate, a detection area and a sampling area; the sampling area is provided with a microneedle array, and the surface of the microneedle array is modified with biomolecules capable of being specifically combined with cervical cells; the detection area is provided with a nano sensor, and a specific probe aiming at HPV-DNA is fixed on the surface of an electrode; the detection module comprises a signal reading circuit and a signal processing circuit; the signal reading circuit is used for reading the electric signal detected by the nano sensor and converting the electric signal into a digital signal; and the signal processing circuit is used for analyzing and processing the digital signal to obtain an HPV-DNA quantitative detection result. According to the method, deformation self-correction is realized in the biological patch for the first time through a three-stage technical closed loop of spatial redundancy layout, continuous wrinkle modeling and multi-electrode cooperative calculation.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and more specifically, to a cervical self-examination HPV-DNA nanosensor patch device. Background Technology

[0002] Cervical cancer is one of the most common malignant tumors among women worldwide, and its occurrence is closely related to human papillomavirus (HPV) infection. Currently, commonly used clinical methods for HPV testing mainly include traditional techniques such as cytological examination (e.g., Pap smear) and HPV-DNA testing.

[0003] However, while existing methods can provide a certain degree of accuracy, they have significant shortcomings: (1) They rely on specialized medical equipment and medical personnel: the testing process needs to be carried out in medical institutions, with professional personnel collecting and analyzing samples, which increases time and economic costs. (2) The testing process is complex and time-consuming: samples need to be sent to laboratories for processing, involving multiple preprocessing steps (such as DNA extraction and amplification), resulting in results taking several days or even weeks to obtain. (3) They are not conducive to large-scale screening and daily monitoring: for women (especially in resource-scarce areas), frequent medical visits are inconvenient, making it difficult to achieve early screening and real-time self-monitoring, thus delaying the opportunity for prevention and treatment.

[0004] Therefore, developing a convenient, fast, and accurate cervical self-examination HPV-DNA detection device is of great practical significance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a cervical self-examination HPV-DNA nanosensor patch device. Users can use this patch device to perform sampling and testing on the cervix themselves without the need for professional medical personnel, greatly improving the convenience of testing and facilitating cervical cancer screening in a wider population.

[0006] The above-mentioned technical objective of the present invention is achieved through the following technical solution:

[0007] A cervical self-examination HPV-DNA nanosensing patch device includes a patch structure and a detection module;

[0008] The patch structure includes a flexible substrate, a detection area, and a sampling area arranged sequentially from bottom to top;

[0009] The sampling area is equipped with a microneedle array made of biocompatible material, and the surface of the microneedle array is modified with biomolecules that can specifically bind to cervical cells for collecting cervical cell samples.

[0010] The detection area is equipped with a nanosensor containing an electrode modified with gold nanoparticles, and the surface of the electrode is immobilized with a specific probe for HPV-DNA.

[0011] The detection module includes a signal reading circuit and a signal processing circuit;

[0012] The signal reading circuit is used to read the electrical signal detected by the nanosensor and convert the electrical signal into a digital signal.

[0013] The signal processing circuit is used to analyze and process the digital signal to obtain the HPV-DNA quantitative detection result.

[0014] Furthermore, the biocompatible material is a polylactic acid-glycolic acid copolymer, and the microneedle array is prepared using micromold forming technology.

[0015] Furthermore, the surface of the microneedle array is modified with chitosan and linked with a monoclonal antibody that can specifically recognize cervical cell surface antigens.

[0016] Furthermore, the sampling area and the detection area are connected by a hydrophilic microfluidic channel layer.

[0017] Furthermore, the nanosensor includes at least three parallel-connected electrodes;

[0018] Each of the aforementioned electrodes is provided with a plurality of the aforementioned microneedle arrays at intervals;

[0019] The microneedle arrays configured on adjacent electrodes are staggered.

[0020] The difference in the number of microneedle arrays configured on adjacent sub-electrodes is 1.

[0021] Furthermore, the signal processing circuit includes:

[0022] The resistance calculation unit is used to calculate the actual resistance of the unit after the detection is completed, based on the digital signals of multiple electrodes and the configuration parameters of the sampling area and the detection area.

[0023] The quantitative calculation unit is used to convert the actual resistance of the unit into the quantitative detection result of HPV-DNA.

[0024] Furthermore, the configuration parameters include the number of sampling sub-regions in the sub-electrode, the number of interval regions, and the unit resistance of the sub-electrode.

[0025] Furthermore, the formula for calculating the actual resistance of the unit is as follows:

[0026] ;

[0027] in, The actual resistance of the unit; The excitation voltage; This is the current value corresponding to the first electrode. This is the current value corresponding to the second electrode. This is the current value corresponding to the third electrode. This refers to the number of inter-electrode spacing regions in the first sub-electrode. This represents the number of sampling sub-regions in the first electrode. This is the unit resistance.

[0028] Furthermore, the HPV-DNA quantitative detection results are positively correlated with the actual resistance of the unit.

[0029] Furthermore, the device is also equipped with a signal line; one end of the signal line is plugged into the patch structure, and the other end is plugged into the detection module.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] 1. The present invention provides a cervical self-examination HPV-DNA nanosensor patch device, which allows users to use the patch device to perform sampling and testing on the cervix without the need for professional medical personnel, greatly improving the convenience of testing and facilitating cervical cancer screening in a wider population.

[0032] 2. The entire process from sampling to obtaining test results can be completed in a short time. Compared with traditional HPV testing methods, this invention significantly shortens the testing cycle and can provide users with timely test feedback.

[0033] 3. This invention uses gold nanoparticles to modify electrodes and specific probes, which makes the nanosensor patch highly sensitive and specific to HPV-DNA, and can accurately detect low concentrations of HPV-DNA, effectively reducing the risk of missed diagnosis and misdiagnosis.

[0034] 4. By staggering the microneedle array between adjacent sub-electrodes, this invention can accurately calculate the actual resistance of the unit based on the current values ​​of the three sub-electrodes without knowing the specific linear folds. Attached Figure Description

[0035] The accompanying drawings, which are included to provide a further understanding of embodiments of the invention and form part of this application, do not constitute a limitation thereof. In the drawings:

[0036] Figure 1 This is a schematic diagram of the patch structure distribution in an embodiment of the present invention;

[0037] Figure 2 This is a schematic diagram of the distribution of the microneedle array in an embodiment of the present invention;

[0038] Figure 3 This is a schematic diagram of the structure of the nanosensor in an embodiment of the present invention;

[0039] Figure 4 This is a schematic diagram of the distribution of the sampling area in an embodiment of the present invention;

[0040] Figure 5 This is a schematic diagram of the layer structure of the patch structure in an embodiment of the present invention;

[0041] Figure 6 This is a schematic diagram of linear folds in an embodiment of the present invention;

[0042] Figure 7 This is a simplified schematic diagram of linear folds in an embodiment of the present invention.

[0043] The attached diagram shows the markings and corresponding component names:

[0044] 1. Flexible substrate; 2. Nanosensor; 3. Sampling area; 4. Dividing electrode; 5. Microneedle array; 6. Hydrophilic microfluidic channel layer. Detailed Implementation

[0045] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments and accompanying drawings. The illustrative embodiments and descriptions of the present invention are only used to explain the present invention and are not intended to limit the present invention.

[0046] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly or indirectly attached to that other component. When a component is referred to as being "connected to" another component, it can be directly or indirectly connected to that other component.

[0047] It should be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the present invention.

[0048] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0049] Example: A cervical self-examination HPV-DNA nanosensor patch device, including patch structure and detection module.

[0050] like Figure 1 As shown, the patch structure includes a flexible substrate 1, a detection area, and a sampling area 3 arranged sequentially from bottom to top. The sampling area 3 is equipped with a microneedle array 5 made of biocompatible material, and the surface of the microneedle array 5 is modified with biomolecules that can specifically bind to cervical cells for collecting cervical cell samples. The detection area is equipped with a nanosensor 2 containing an electrode modified with gold nanoparticles, and the electrode surface is immobilized with a specific probe targeting HPV-DNA.

[0051] The detection module includes a signal reading circuit and a signal processing circuit; the signal reading circuit is used to read the electrical signal detected by the nanosensor 2 and convert the electrical signal into a digital signal; the signal processing circuit is used to analyze and process the digital signal to obtain the HPV-DNA quantitative detection result.

[0052] In some examples, such as Figure 2 As shown, for microneedle array 5: polylactic acid-glycolic acid copolymer (PLGA) can be used as the biocompatible material for microneedle array 5. It has both degradability and mechanical strength, which facilitates penetration of the cervical mucosa layer. Microneedle array 5 is prepared by micromold forming technology, and chitosan is modified on its surface. Chitosan adsorbs cervical exfoliated cells (negatively charged) by positive charge, which improves the collection efficiency. Furthermore, monoclonal antibodies that can specifically recognize cervical cell surface antigens are linked to achieve specific capture, reduce impurity interference, and enhance the collection ability of cervical cells.

[0053] For the fabrication of nanosensor 2: First, gold nanoparticles were prepared and modified onto the electrode surface. Then, a specific probe targeting HPV-DNA was immobilized on the surface of the gold nanoparticles using a chemical modification method, thus constructing nanosensor 2 for detecting HPV-DNA. The electrode substrate was fabricated using conductive materials such as gold, platinum, or carbon electrodes.

[0054] For patch assembly: The prepared microneedle array 5 and nanosensor 2 are fixed on the flexible substrate 1 according to the design requirements to complete the assembly of the nanosensor patch. The flexible substrate 1 can be made of materials such as polyimide or polylactic acid.

[0055] It should be noted that the above-mentioned specific probes, chitosan, and monoclonal antibodies targeting HPV-DNA are all publicly available technologies and can be consistent with the detection standards, so they will not be described in detail here.

[0056] Furthermore, the detection module in this invention can be packaged as a standalone handheld device. The patch structure also includes an interface, with a power supply terminal connected to one end of the nanosensor 2 and a signal terminal connected to the other end of the nanosensor 2. The detection module can be connected to the patch structure via a signal line, which includes a power line and a signal sub-line. One end of the signal line is plugged into the patch structure, and the other end is plugged into the detection module. Alternatively, the detection module can also be connected to the patch structure wirelessly, without limitation.

[0057] The patch device of the present invention is also equipped with a protective layer, such as polyethylene terephthalate (PET) film, which covers the sampling area 3 and the detection area to prevent contamination and physical damage, and is peeled off before use.

[0058] Before use, an excitation voltage is supplied to the nanosensor 2 through the power supply in the detection module, and the initial electrode current value output by the nanosensor 2 is detected. During use, the microneedle array 5 of the patch is gently pressed onto the cervical surface. The microneedles penetrate the cervical tissue to collect cell samples. After being collected by the microneedle array 5, the cell samples are transferred to the detection area. If HPV-DNA is present in the cell samples, it will hybridize with the specific probes on the nanosensor 2. The complex produced by the reaction hinders the transfer of electrons between gold nanoparticles, thereby changing the electron transport characteristics of the gold nanoparticles (increasing impedance). This changes the current magnitude under the same excitation voltage. By comparing and analyzing the actual current value collected during use with the initial electrode current value, quantitative detection of HPV-DNA can be achieved.

[0059] Quantitative detection can be achieved by directly comparing the magnitude of current changes or the magnitude of resistance changes in nanosensor 2. This can be done by matching the current or resistance change value with a reference interval, or by matching the actual current or resistance value with a reference interval. Each reference interval corresponds to a quantitative result for HPV-DNA, and the reference intervals differ depending on the matching method. The reference interval and the corresponding quantitative result for HPV-DNA are determined using conventional experimental calibration methods, which will not be described in detail here.

[0060] Because the cervical surface is not perfectly flat, when the patch is applied to the cervical surface, there is a possibility that the microneedle array 5 may not penetrate the cervical tissue, leading to significant errors in the test results. Furthermore, the entire testing process takes a considerable amount of time, and changes in the user's posture can easily cause the patch to wrinkle, also resulting in significant errors in the test results.

[0061] like Figure 3 and Figure 4 As shown, the nanosensor 2 in this invention is composed of three parallel sub-electrodes 4, which are insulated from each other. Each sub-electrode 4 is provided with multiple microneedle arrays 5 at intervals. The microneedle arrays 5 of adjacent sub-electrodes 4 are staggered, and the difference in the number of microneedle arrays 5 of adjacent sub-electrodes 4 is 1.

[0062] In order to reduce the complexity of subsequent quantitative detection analysis, the interval between the two microneedle arrays 5 in one electrode 4 of this invention is exactly the width of one microneedle array 5. The sampling area 3 is composed of all microneedle arrays 5, and the detection area is composed of the area in the electrode that is directly opposite to all microneedle arrays 5.

[0063] like Figure 5 As shown, the sampling area 3 and the detection area are connected by a hydrophilic microfluidic layer 6. The hydrophilic microfluidic layer 6 can be made of the same biocompatible material as described above, and sample migration is achieved by capillary action or the hydrophilicity of the material.

[0064] Taking resistance analysis as an example, the signal processing circuit includes a resistance calculation unit and a quantitative calculation unit. The resistance calculation unit calculates the actual resistance of the unit after detection in the detection area based on the digital signals from multiple electrodes 4 and the configuration parameters of the sampling area 3 and the detection area. The quantitative calculation unit converts the actual resistance of the unit into the HPV-DNA quantitative detection result. The configuration parameters include the number of sampling sub-regions in the electrodes 4, the number of interval regions, and the unit resistance of the electrodes 4. Each region of the microneedle array 5 is a sampling sub-region.

[0065] It should be noted that the signal processing circuit can be implemented using algorithms built into the processor, or it can be implemented using arithmetic circuits for addition, subtraction, multiplication, and division; there are no restrictions on this.

[0066] like Figure 3 and Figure 4 As shown, the first electrode 4 has 4 ( ) sampling sub-regions and 3 ( The first electrode 4 has 4 sampling sub-regions and 3 interval regions. The second electrode 4 has 3 sampling sub-regions and 4 interval regions. Assume the total resistance of all electrode 4 is... Each electrode 4 is composed of 7 unit resistors connected in series, so the unit resistor One-seventh Excitation voltage Unit resistance All data are known.

[0067] Because the patch device is small in size, the wrinkles are generally linear or nearly linear. Therefore, the microneedle array 5 and the spacing region are simplified by dot matrix processing. Errors can also be reduced by treating the failure of a single sampling sub-region as a linear wrinkle. Figure 6 and Figure 7 As shown, a, b, c, and d represent different linear wrinkles or equivalent linear wrinkles. The sampling sub-region is simplified to a black dot, and the interval region is simplified to a hollow dot. A wrinkle at the center of the sampling sub-region is considered a failure value of 1; while a wrinkle at the center of the interval region is considered a failure value of 0; and the failure value between the center of the sampling sub-region and the center of the interval region changes linearly from 1 to 0.

[0068] Therefore, assuming the failure value of the first electrode 4 is... The failure value of the third electrode 4 is In the case of misaligned distribution, the failure value of the second electrode 4 is .

[0069] According to the excitation voltage and the current values ​​of each of the 4 sub-electrodes , , Establish the resistance of each electrode 4 after detection , , The system of equations is as follows:

[0070] ;

[0071] in, The resistance after detection by the first electrode 4; The resistance after detection by the second electrode 4; The resistance after detection by the third electrode 4; The resistance value after detection of the effective sampling sub-region in the first electrode 4; The resistance value after detection of the effective sampling sub-region in the second electrode 4; The resistance value is the result of detection of the effective sampling sub-region in the third electrode 4.

[0072] Without significant error effects, the final actual resistance of the unit is calculated by averaging multiple resistance values. Therefore, the apparent actual resistance R of the unit is: = = = Through the and After elimination, the actual resistance of the unit is obtained as follows:

[0073] ;

[0074] in, The actual resistance of the unit; The excitation voltage; This is the current value corresponding to the first electrode 4; This is the current value corresponding to the second electrode 4; This is the current value corresponding to the third electrode 4; This refers to the number of inter-dividend regions in the first electrode 4; This refers to the number of sampling sub-regions in the first electrode 4; This is the unit resistance.

[0075] As can be seen from the calculation expression of the actual resistance of the unit, by staggering the micro-needle array 5 between adjacent sub-electrodes 4, the present invention can accurately calculate the actual resistance of the unit based on the current value of the three sub-electrodes 4 without knowing the specific linear folds.

[0076] Working process: When using this device, the microneedle array 5 of the patch is gently pressed onto the surface of the cervix. The microneedles penetrate the cervical tissue to collect cell samples. After being collected by the microneedle array 5, the cell samples are transferred to the detection area. If HPV-DNA is present in the cell samples, it will hybridize with the specific probe on the nanosensor 2. The complex produced by the reaction hinders the transfer of electrons between gold nanoparticles, thereby changing the electron transport characteristics of the gold nanoparticles (increasing the impedance). This changes the current magnitude under the same excitation voltage. By comparing and analyzing the actual current value collected during use with the initial electrode current value, quantitative detection of HPV-DNA can be achieved.

[0077] Those skilled in the art will understand that embodiments of this application can be provided as methods, systems, or computer program products. Therefore, this application can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, this application can take the form of a computer program product embodied on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0078] This application is described with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of this application. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, generate instructions for implementing the flowchart... Figure 1 One or more processes and / or boxes Figure 1 A device that provides the functions specified in one or more boxes.

[0079] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing device to function in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means, which are implemented in a process Figure 1 One or more processes and / or boxes Figure 1 The function specified in one or more boxes.

[0080] These computer program instructions may also be loaded onto a computer or other programmable data processing equipment to cause a series of operational steps to be performed on the computer or other programmable equipment to produce a computer-implemented process, thereby providing instructions that execute on the computer or other programmable equipment for implementing the process. Figure 1 One or more processes and / or boxes Figure 1 The steps of the function specified in one or more boxes.

[0081] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A cervical self-examination HPV-DNA nanosensor patch device, characterized in that, Includes patch structure and detection module; The patch structure includes a flexible substrate (1), a detection area, and a sampling area (3) arranged sequentially from bottom to top. The sampling area (3) is equipped with a microneedle array (5) made of biocompatible material, and the surface of the microneedle array (5) is modified with biomolecules that can specifically bind to cervical cells for collecting cervical cell samples. The detection area is equipped with a nanosensor (2) containing an electrode modified with gold nanoparticles, and the surface of the electrode is immobilized with a specific probe for HPV-DNA. The detection module includes a signal reading circuit and a signal processing circuit; The signal reading circuit is used to read the electrical signal detected by the nanosensor (2) and convert the electrical signal into a digital signal. The signal processing circuit is used to analyze and process the digital signal to obtain the HPV-DNA quantitative detection result.

2. The cervical self-examination HPV-DNA nanosensor patch device according to claim 1, characterized in that, The biocompatible material is a polylactic acid-glycolic acid copolymer, and the microneedle array is prepared by micromold forming technology (5).

3. The cervical self-examination HPV-DNA nanosensor patch device according to claim 1, characterized in that, The surface of the microneedle array (5) is modified with chitosan and linked with a monoclonal antibody that can specifically recognize cervical cell surface antigens.

4. The cervical self-examination HPV-DNA nanosensor patch device according to claim 1, characterized in that, The sampling area (3) and the detection area are connected by a hydrophilic microfluidic layer (6).

5. The cervical self-examination HPV-DNA nanosensor patch device according to claim 1, characterized in that, The nanosensor (2) includes at least three parallel-connected sub-electrodes (4); Each of the said electrode (4) is provided with a plurality of said microneedle arrays (5) at intervals; The microneedle arrays (5) configured on adjacent electrodes (4) are staggered. The difference in the number of microneedle arrays (5) configured on adjacent sub-electrodes (4) is 1.

6. The cervical self-examination HPV-DNA nanosensor patch device according to claim 5, characterized in that, The signal processing circuit includes: The resistance calculation unit is used to calculate the actual resistance of the unit after the detection is completed, based on the digital signals of multiple sub-electrodes (4) and the configuration parameters of the sampling area (3) and the detection area. The quantitative calculation unit is used to convert the actual resistance of the unit into the quantitative detection result of HPV-DNA.

7. The cervical self-examination HPV-DNA nanosensor patch device according to claim 6, characterized in that, The configuration parameters include the number of sampling sub-regions in the sub-electrode (4), the number of interval regions, and the unit resistance of the sub-electrode (4).

8. The cervical self-examination HPV-DNA nanosensor patch device according to claim 6, characterized in that, The formula for calculating the actual resistance of the unit is: ； in, The actual resistance of the unit; The excitation voltage; This is the current value corresponding to the first electrode. This is the current value corresponding to the second electrode. This is the current value corresponding to the third electrode. This refers to the number of inter-electrode spacing regions in the first sub-electrode. This refers to the number of sampling sub-regions in the first electrode. This is the unit resistance.

9. The cervical self-examination HPV-DNA nanosensor patch device according to claim 6, characterized in that, The results of the HPV-DNA quantitative detection are positively correlated with the actual resistance of the unit.

10. The cervical self-examination HPV-DNA nanosensor patch device according to claim 1, characterized in that, The device is also equipped with a signal line; one end of the signal line is plugged into the patch structure, and the other end is plugged into the detection module.

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