CN220568810U

CN220568810U - Paper chip device

Info

Publication number: CN220568810U
Application number: CN202321910629.0U
Authority: CN
Inventors: 苏磊; 谢媛婷
Original assignee: Shenzhen University
Current assignee: Shenzhen University
Priority date: 2023-07-19
Filing date: 2023-07-19
Publication date: 2024-03-08
Anticipated expiration: 2033-07-19

Abstract

The utility model relates to the technical field of instant detection, in particular to a paper chip device, which comprises a connecting pipe and a negative pressure generator, wherein a paper chip is arranged in a lumen of the connecting pipe, one end of the connecting pipe is communicated with a hollow micro needle, the other end of the connecting pipe is communicated with the negative pressure generator during detection, a pore canal communicated with the connecting pipe is arranged on the hollow micro needle, tissue fluid can be directly extracted from the skin through the hollow micro needle under the action of the negative pressure generator, the tissue fluid flows into the connecting pipe from the hollow micro needle, the tissue fluid is fully contacted with the paper chip in the connecting pipe, and then the tissue fluid is rapidly analyzed and immediately detected by the paper chip, and the detection result can be obtained within 10 minutes.

Description

Paper chip device

Technical Field

The utility model relates to the technical field of instant detection, in particular to a paper chip device.

Background

Point-of-care testing devices (POCT device) capable of meeting the needs of on-site detection, easy operation, rapid monitoring of health conditions, and even rapid diagnosis of diseases has attracted considerable attention and has a huge and still rapidly growing global market. Blood is currently the most common biological fluid sample for POCT, but has a number of drawbacks associated with invasive sampling. For example, currently available intravenous or fingertip blood sampling methods can cause pain, trauma, and risk of infection to the patient. Furthermore, blood sampling procedures often require trained medical professionals. The tissue fluid contains most of the components present in blood, including inorganic salts, small physiological molecules, RNAs, circulating proteins, antibodies, hormones, exosomes, antibiotics, and dietary-related metabolites (e.g., alcohol, caffeine), etc., which can be the detection targets. And the collection of tissue fluid can be relatively simple, easy to operate, pain-free and risk-free, thus becoming a good biological sample for a new generation of instant detection devices.

Microneedles (microscales) have a hollow or solid needle-like structure with needle tip sizes as small as tens of microns. It was originally used for transdermal delivery of drugs and vaccines, and has recently been developed for painless extraction of subcutaneous tissue fluid in a minimally invasive manner. Heretofore, various materials such as silicon, metals, and polymers have been used to fabricate microneedles. The tissue fluid extracted by the micropins can be used for health monitoring, detection and disease diagnosis. However, the existing detection method based on the tissue fluid extracted by the microneedle is long in time consumption, inconvenient to operate and more in operation steps, and often cannot meet the requirement of instant detection. For example, hydrogel microneedles are currently the most widely used method of interstitial fluid extraction. Detection methods based on hydrogel microneedle extraction of tissue fluids rely on swelling of the hydrogel and diffusion of tissue fluids therein to extract the tissue fluids. However, the diffusion process of tissue fluids in hydrogels is slow, often requiring tens of minutes, and the extraction is low (typically less than 10 microliters), resulting in a failure to achieve rapid detection (typically requiring tens of minutes to display the results). In addition, some technical means place the detection system inside the hydrogel microneedle, so that although the detection speed is increased, there is a biosafety risk of leakage of chemical reagents.

Therefore, there is a need to provide a detection device or technique that is easy to operate, performs on-site detection, detects rapidly, and is free of biosafety risks.

Disclosure of Invention

Therefore, the utility model aims to overcome the defect that the components in tissue fluid cannot be rapidly and simply detected on site to monitor the health condition in the prior art, thereby providing a paper chip device.

The utility model provides a paper chip device, which comprises a connecting pipe and a negative pressure generator, wherein a paper chip is arranged in a lumen of the connecting pipe, one end of the connecting pipe is communicated with a hollow microneedle, the other end of the connecting pipe is communicated with the negative pressure generator during detection, and a pore canal communicated with the connecting pipe is arranged on the hollow microneedle.

According to the paper chip device provided by the utility model, under the action of the negative pressure generator, tissue fluid can be directly extracted from the skin through the hollow micro-needle, the tissue fluid flows into the connecting pipe from the hollow micro-needle, the tissue fluid is fully contacted with the paper chip in the connecting pipe, and then the tissue fluid is rapidly analyzed and immediately detected by the paper chip, and the detection result can be obtained within 10 minutes.

In some preferred embodiments, a cavity table is further arranged between the connecting pipe and the hollow microneedle, a cavity structure is formed inside the cavity table, a cavity of the cavity table is communicated with a pore canal of the hollow microneedle, and the pore canal of the hollow microneedle is communicated with the connecting pipe through the cavity table.

The paper chip device provided by the utility model is provided with a continuous channel from the hollow microneedle hole channel to the cavity of the cavity table, then to the tube cavity of the connecting tube and finally to the negative pressure generator. The cavity structure inside the cavity table is a converging place of tissue fluid extracted by the hollow micro needles, and simultaneously, the tissue fluid is conveyed to an external buffer space, and the place is communicated with an external connecting pipe. When in use, the hollow micro-needle is inserted into skin, and tissue fluid can automatically enter and be stored in the hollow micro-needle, the cavity table, the connecting pipe and the negative pressure generator under the driving of capillary action and negative pressure. When the device is used for extracting tissue fluid, the hollow micro-needle is pressed to pierce the skin, then the connecting pipe is communicated with the negative pressure generator, and after a continuous channel from the hollow micro-needle channel to the hollow cavity of the hollow cavity platform to the connecting pipe lumen to the negative pressure generator is formed, no manual operation is needed to take the tissue fluid, and only the tissue fluid is required to wait for automatically entering the hollow cavity platform, the connecting pipe and the negative pressure generator through the hollow micro-needle.

In some preferred embodiments, a connecting portion is provided at one side of the cavity table, which is in communication with the connecting pipe, and the cavity of the cavity table is in communication with the connecting pipe through the connecting portion. The setting of connecting portion is convenient for be connected cavity platform and connecting pipe for cavity platform and connecting pipe can adopt different materials, for example, the connecting pipe can adopt plastics elastic material, and cavity platform adopts hard material, improves the leakproofness of both junction.

In certain preferred embodiments, the hollow microneedles are provided with a plurality of channels. The pore canal on the hollow microneedle is arranged on the surface of the hollow microneedle, penetrates through the bottom surface of the cavity table and is communicated with the cavity of the cavity table, and the plurality of pore canals on the hollow microneedle can improve the extraction speed of tissue fluid and simultaneously avoid the condition that the extraction efficiency of the tissue fluid is reduced and even fails due to the blockage of a single pore canal.

In the utility model, the cross section of the cavity table is square, or elliptical, or circular, or a combination of square, elliptical and circular. The top surface of the cavity table is provided with a plane, a convex or a concave structural form. The top surface of the cavity table may be planar, or convex, or concave in configuration when viewed from the side.

In certain preferred embodiments, the height of the cavity structure is 0.5-2.5mm. Preferably 1mm.

In certain preferred embodiments, the cavity floor is a planar structure. The cavity table is in a planar structure, but can still be closely attached to the skin when the cavity table is pressed to cause the micro-needle to pierce the skin and during the tissue fluid extraction process.

More preferably, the cavity floor has a flexible or deformable structure. The bottom surface is flexible or is the deformable structure, when pressing the cavity platform and making the micropin puncture skin and in the tissue fluid extraction process, the cavity platform can more closely laminate skin.

In some preferred embodiments, the cavity floor is a curved structure, flexible or deformable. When the cavity table is pressed to enable the micro-needle to pierce the skin and in the tissue fluid extraction process, the cavity table with the curved bottom surface can still be closely attached to the skin.

In the utility model, the number of the connecting parts is a plurality of. The side surface of the cavity table can be provided with a plurality of through connecting parts for respectively connecting different connecting pipes and negative pressure generators, so that one cavity table device can be provided with a plurality of sets of negative pressure generators, and the tissue fluid extraction and storage capacity of the device for rapidly extracting and storing tissue fluid based on the negative pressure of the micro needle is improved.

More preferably, the number of the connection parts is 1 to 4.

In certain preferred embodiments, the connecting portion is a cylindrical structure. The connecting pipe is connected with the connecting part in a nested way, is a hose and is nested at the outer side of the connecting part.

In some preferred embodiments, the connecting tube is a through tube with two open ends, and a hollow connecting tube cavity is arranged between the two open ends.

The inner diameter of the connecting pipe is 1-10mm.

In certain preferred embodiments, a support body is disposed within the cavity that connects the top and bottom of the cavity table.

The supporting body has the function of supporting the cavity structure, and avoids the problem that the cavity is closed due to the deformation of the cavity table structure in the manufacturing process, the storage process and the use process, so that the opening of the hollow microneedle below is blocked, or tissue fluid converged in the cavity structure is blocked, thereby influencing the extraction of the tissue fluid. Simultaneously, the supporting body can also reduce the dead volume of the hollow cavity of the hollow table, and reduce the residual of tissue fluid extracted by the hollow micro needle in the hollow cavity of the hollow table.

In certain preferred embodiments, the support is disposed away from the opening of the hollow microneedle. The main purpose of avoiding the opening is to avoid the support body from blocking the pore canal of the hollow microneedle and interfering with the extraction of subcutaneous body fluid, so that tissue fluid can smoothly pass through the connecting pipe.

Preferably, the number of the supporting bodies is 2-4.

Preferably, the support bodies are arranged parallel to each other or around the center of the cavity.

More preferably, the support bodies are not connected to each other. More preferably, the support body is not connected to the inner wall of the cavity.

Preferably, the support body is provided with a through hole. The through holes on the support body are used for allowing subcutaneous tissue fluid in the cavity to flow, and tissue fluid extracted through the hollow microneedles is not blocked.

More preferably, the hollow microneedles are provided in plurality to form a microneedle array.

Preferably, the tip circumference of the hollow microneedle is smaller than the bottom circumference of the hollow microneedle.

Preferably, the hollow microneedle comprises a morphology including, but not limited to, conical, square conical, pyramidal, multiple conical, multiple square conical, multiple pyramidal, or a combination thereof.

In certain preferred embodiments, the hollow microneedle is a hollow microneedle array of 5×5 to 20×20 hollow microneedles having an area of 0.28 to 46.24cm ² . The microneedle array at this scale takes into account the extraction capacity of the hollow microneedles and the size of the patch, which meets the extraction requirements of the assay.

In certain preferred embodiments, the hollow microneedles have a length (or height) of 300-1200 μm. The hollow microneedle with the length is insufficient to contact nerve endings in dermis, has small wound on human skin, and reduces pain.

In certain preferred embodiments, the hollow microneedles are spaced from adjacent hollow microneedles at a center-to-center distance of 300-3000 μm. The center distance can meet the requirements of the device size in different scenes.

In certain preferred embodiments, the number of said channels per hollow microneedle is from 1 to 4.

In certain preferred embodiments, the pore channels have an inner diameter of 10 to 1000 μm.

Preferably, the device further comprises a storage device, and the negative pressure generator and the storage device can be integrated devices or separated devices.

Preferably, the integrated device includes, but is not limited to, an integrated device that is pre-evacuated to different vacuum levels, and that uses its negative pressure to collect and simultaneously store a sample. More preferably, the integrated negative pressure generating and storing device includes, but is not limited to, a vacuum sampling tube, or a reduced pressure sampling tube. When in use, the extraction end is pressed firstly, so that the hollow micro-needle is penetrated into the skin; then one end of the connecting tube with the needle head is inserted into a vacuum sampling tube, or a decompression sampling tube, and subcutaneous body fluid is rapidly extracted and transferred from the lower part of the skin to the connecting tube, the vacuum sampling tube, or the decompression sampling tube by utilizing the negative pressure provided by the vacuum sampling tube.

Optionally, the separate device includes, but is not limited to, a device having a reservoir prior to the negative pressure generating device. The negative pressure generating and storing separation device refers to a device which drives a sample to flow and extract the sample through a negative pressure space, and stores the sample on a channel of which the negative pressure drives the sample to flow, wherein the storage space is separated from the space of the negative pressure generator and is not the same space.

Preferably, the height of the cavity is 0.5-2.5mm.

The hollow micro-needle and the cavity table are made of materials including but not limited to organic high molecular polymers and inorganic materials.

More preferably, the inorganic material comprises a metallic, inorganic nonmetallic material.

More preferably, the organic high molecular polymer includes but is not limited to methacryloylated gelatin, methacryloylated hyaluronic acid, methacryloylated polyethylene glycol and other methacrylic end polymers, polydimethylsiloxane, polyvinyl alcohol, polyurethane, polyethylene glycol, photo-curable resin.

More preferably, the photocurable resin is an existing conventional biocompatible photocurable resin.

In a preferred embodiment, the cavity table and the microneedle array are integrally formed.

The utility model also provides a preparation method of the cavity table and the micro-needle array, and the cavity table and the array are prepared by adopting an integral molding process.

In a preferred embodiment, the integral molding process includes, but is not limited to, 3D printing, micro-casting, templating, laser etching.

The paper chip is loaded in the lumen of the connecting pipe and is close to one side of the hollow microneedle; and/or the paper chip is wholly located in the connecting pipe or partly located in the connecting pipe and partly located in the cavity.

In the utility model, the width of the paper chip is smaller than the inner diameter of the connecting pipe. Preferably, the width of the paper chip is 70-90% of the size of the inner diameter of the connection pipe. In particular, the paper chip may have a length of 5-15mm. The inner diameter of the connecting tube may be 1-10mm.

In the utility model, the paper chip can be a colorimetric test strip, a chemiluminescent test strip and the like, and can also be a lateral chromatography test strip and the like.

The paper chip is pre-modified with a chemical sensing system capable of detecting and analyzing tissue fluid components, and response signals comprise color development or self-luminescence. The chemical sensing system can be prepared by adopting the existing conventional method.

Alternatively, the paper substrate of the paper chip may be one of nitrocellulose membrane or filter paper;

optionally, the paper chip is modified by detection functionalization, and the whole paper chip substrate can be directly soaked in a solution containing a chemical sensing reagent for a period of time, taken out and dried.

Optionally, the paper chip is modified by detection functionalization, and the solution containing the chemical sensing reagent can be directly dripped on the whole paper chip substrate and then dried.

Optionally, the paper chip can also print patterns on a paper chip substrate by using a wax-spraying printer to form a plurality of hydrophilic areas as reaction areas and the rest is a hydrophobic area; the hydrophobic regions form hydrophobic blocks between the reaction regions; the hydrophilic areas of the paper chip can be modified with different chemical sensing systems for detecting different components of tissue fluid.

Alternatively, the hydrophilic areas formed may be located on both sides of the paper chip when printing a pattern on the paper chip substrate using a wax-jet printer.

In the utility model, the color development or luminescence caused by the action of the tissue-related components and the chemical sensing system embedded in the paper chip can be collected by the image collecting equipment, and then the color data of the color development or the luminous intensity data are obtained through analysis of image processing software, so that the content information of the tissue-related components is obtained through comparison with a standard system.

Alternatively, the image capture device may be a cell phone, or a camera.

Alternatively, the Image processing software may be Image J, or matlab, or python.

In the utility model, the paper chip reacts with the entered tissue fluid, and then the T line and C line signals of the lateral chromatography detection test paper are directly read out visually, so that the qualitative analysis of the tissue fluid extracted by the hollow microneedle is realized.

Alternatively, the lateral chromatography test paper chip may be a self-made lateral chromatography test paper or a commercially available lateral chromatography test paper.

Alternatively, a self-made lateral chromatography test strip, consisting of a sample pad, conjugate release pad, capture probe immobilized membrane (typically nitrocellulose membrane), and an adsorption pad, is mounted on the surface of an inert backing material.

Alternatively, the capture probe is one of an antibody and a nucleic acid aptamer.

Optionally, when the lateral chromatography test paper chip adopts the commercial lateral chromatography test paper, the lateral chromatography test paper needs to be taken out from the test card, then the water absorption pad at the rear end is removed, the sample injection area at the front end is shortened, but the sample binding pad is kept intact, and then the size is cut, so that the lateral chromatography test paper can be inserted into the connecting pipe.

Alternatively, the lateral chromatography test strip can be, but is not limited to, early pregnancy test strip, new coronavirus antigen test strip, hepatitis B virus surface antigen test strip, human immunodeficiency virus antibody test strip, hepatitis C virus antibody test strip, treponema pallidum antibody test strip, illegal addition test strip of health food ingested by the body, cosmetic harmful substance test strip ingested by the body, and metal ion test strip ingested by the body.

The technical scheme of the utility model has the following advantages:

1. according to the paper chip device provided by the utility model, under the action of the negative pressure generator, tissue fluid can be directly extracted from the skin through the hollow micro-needle, the tissue fluid flows into the connecting pipe from the hollow micro-needle, the tissue fluid is fully contacted with the paper chip in the connecting pipe, and then the tissue fluid is rapidly analyzed and immediately detected by the paper chip, and the detection result can be obtained within 10 minutes.

In addition, the utility model realizes the detection of tissue fluid and has the advantages of simple operation, quick field detection and no biological safety risk.

2. The paper chip in the paper chip device provided by the utility model can be directly placed in the lumen of the connecting pipe as a color development or self-luminous platform, and other mechanisms and additional devices are not required to be added, so that the paper chip loading mode is very simple and convenient. For detection based on color development sensing and lateral chromatography, the color change can be directly observed by naked eyes, and the mode of reading out the detection result is very simple and convenient.

3. The chemical sensing system of the paper chip in the paper chip device provided by the utility model has expansibility, and can be used for designing and realizing detection of various important biomarkers, such as glucose, lactic acid, luteinizing hormone, pH and the like.

Drawings

In order to more clearly illustrate the embodiments of the present utility model or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present utility model, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.

Fig. 1 is a schematic view showing the structure of a paper chip device in embodiment 1 of the present utility model;

fig. 2 is a schematic structural view of a paper chip device in embodiment 2 of the present utility model;

FIG. 3 is a schematic diagram showing the connection relationship between a hollow cavity stage and hollow microneedles according to embodiment 2 of the present utility model;

FIG. 4 is a schematic diagram showing the connection relationship between the support and the cavity in embodiment 3 of the present utility model;

fig. 5 is a schematic view showing the structure of a paper chip device in example 4 of the present utility model;

FIG. 6 is a schematic diagram showing the connection relationship between the support and the cavity in embodiment 4 of the present utility model;

FIG. 7 is a scanning electron microscope image of the hollow microneedle of example 2 of the present utility model;

FIG. 8 is a schematic diagram showing the results of verification of the test results using the paper chip device of the present utility model and a commercially available blood glucose meter in Experimental example 1;

reference numerals:

1. a cavity table; 2. hollow microneedles; 3. a paper chip; 4. a connecting pipe; 5. a negative pressure generator; 6. a connection part; 7. a connecting tube lumen; 8. a support body; 9. a reservoir; 10. a cavity; 11. skin tissue.

Detailed Description

The following examples are provided for a better understanding of the present utility model and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the utility model, any product which is the same or similar to the present utility model, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present utility model.

The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.

Example 1

As shown in fig. 1, the present embodiment provides a paper chip device including a paper chip 3, a connection pipe 4, hollow microneedles 2, and a negative pressure generator 5. The paper chip 3 is used for qualitative or quantitative detection of tissue fluid, and the paper chip 3 is pre-modified with a chemical sensing system capable of detecting and analyzing tissue fluid components, and response signals comprise color development or luminescence. The paper chip 3 can be self-made according to the method of the utility model, and can also be obtained by adopting the existing lateral chromatography test paper after cutting. The paper chip 3 is loaded in the lumen of the connecting tube 4 (i.e. the connecting tube lumen 7), and the hollow micro-needle 2 is provided with a pore canal. The connecting pipe 4 is a through pipe with two open ends, and a hollow connecting pipe cavity 7 is arranged between the two open ends. One end of the connecting pipe 4 is communicated with the pore canal on the hollow micro needle 2, and the other end is communicated with the negative pressure generator 5 during detection. Under the negative pressure effect of the negative pressure generator 5, after the hollow micro needle 2 is penetrated into the skin, the tissue fluid flows into the connecting pipe lumen 7 along the pore canal of the hollow micro needle 2, contacts with the paper chip 3 in the connecting pipe lumen 7, and the paper chip 3 carries out rapid analysis and instant detection on the tissue fluid.

The paper chip 3 in this embodiment is loaded in the connecting tube lumen 7 near one side of the hollow microneedle 2. The connecting tube 4 is a transparent tube. In this embodiment, the connecting tube is a transparent connecting tube for connecting a disposable intravenous blood taking needle (specification 0.55x20rw) and the inner diameter of the lumen is 2.5mm. The hollow micro needle 2 is conical in shape. The inner diameter of the pore canal is 300 mu m. The hollow microneedle 2 has a length of 800 μm. The paper chip has a width of 1.5mm and a length of 10mm, can be flatly paved and loaded into the connecting pipe (basically positioned on the cross section of the central pipe diameter), and enough space remains above and below the paper chip, so that the paper chip does not block the pipe cavity of the connecting pipe, and enough physical space is reserved in the pipe cavity of the connecting pipe for liquid to flow.

In this embodiment, the negative pressure generator 5 is an existing vacuum sampling tube, that is, a sampling tube that is used in a hospital for drawing blood and is vacuumized in advance, and the connecting tube 4 is further provided with a hollow needle at one end that is communicated with the negative pressure generator 5. The center of the top cap of vacuum sampling pipe is provided with the plug, after the hollow microneedle 2 is impressed subcutaneously in the time of detecting, stretch into the vacuum sampling pipe with the one end of connecting pipe 4 area syringe needle through the plug in, under the effect of negative pressure, can directly draw the tissue fluid from subcutaneously through hollow microneedle 2, the tissue fluid flows into connecting pipe 4 from the pore canal of hollow microneedle 2, tissue fluid fully contacts with paper chip 3 in the connecting pipe lumen 7, and then utilizes paper chip 3 to carry out quick analysis and real-time detection to the tissue fluid, its testing result can obtain in 10 minutes.

Example 2

As shown in fig. 2 and 3, this embodiment provides a paper chip device, which is different from embodiment 1 in that this embodiment employs a plurality of hollow microneedles 2 to form a microneedle array, and the microneedle array is located on a cavity stage 1. The cavity table 1 is internally provided with a cavity 10 structure. The cavity table 1 is provided with a through connection part 6 on the side surface. The connecting part 6 is of a cylindrical structure, the connecting pipe 4 is connected with the connecting part 6 in a nested manner, the connecting pipe 4 is a hose, and the connecting pipe 4 is nested at the outer side of the connecting part 6.

The top surface of the cavity table 1 is square. The bottom surface of the cavity table 1 is a microneedle array. The micro-needle array is arranged at the bottom of the cavity table 1 and is in structural communication with the cavity 10, the micro-needle array is composed of 5×5 hollow micro-needles 2, and each hollow micro-needle 2 is provided with 2 pore channels penetrating through the bottom surface of the cavity table 1 from the surface of the hollow micro-needle 2. The height of the cavity table 1 is 1mm; the center-to-center distance between the hollow micro needle 2 and the adjacent hollow micro needle 2 is 2000 mu m; the area of the microneedle array was 1.21cm ² 。

The microneedle array and the cavity table 1 in this embodiment are integrally molded by 3D printing using a biocompatible photo-curable resin.

When in use, the micro-needle array is penetrated into the skin tissue 11 by pressing the cavity table 1 and is connected with the vacuum sampling tube, under the action of negative pressure provided by the vacuum sampling tube, tissue fluid in the skin tissue 11 flows into the cavity table 1 through the pore canal of the micro-needle array, and the extracted tissue fluid further enters the vacuum sampling tube through the connecting tube 4 for storage and transportation; the microneedle array needs to be kept in a pressed state after being pressed into the skin, and can be loosened after tissue fluid extraction is completed; after the tissue fluid extraction is completed, the microneedle array is removed from the skin surface, and then the connection tube 4 is separated from the negative pressure generator 5.

Example 3

As shown in fig. 4, this embodiment provides a paper chip device, which is different from embodiment 2 in that the cavity 10 is provided therein with vertical supporting bodies 8, the number of the supporting bodies 8 is 4, and the supporting bodies are disposed around the center of the cavity 10 and are not connected to each other.

Example 4

As shown in fig. 5 and 6, this embodiment provides a paper chip device, which is different from embodiment 2 in that parallel supporting bodies 8 are disposed in the cavity 10, the number of the supporting bodies 8 is 4, and the supporting bodies are disposed in parallel at the bottom surface of the cavity table 1, avoiding the openings of the through-channels of the hollow microneedles 2 in the cavity table 1; the negative pressure generator 5 and the storage 9 are devices with separated negative pressure generation and storage, the storage 9 is communicated with the connecting pipe 4, the connecting point is positioned between the negative pressure generator 5 and the hollow micro-needle 2, the extracted tissue fluid is stored in the storage 9, and the negative pressure is provided by the negative pressure generator 5.

Example 5

The embodiment provides a construction method and application of a paper chip device, comprising the following steps:

1. construction method

(1) Preparation of glucose color paper chip:

0.2g of chitosan was weighed, added to 100.0mL of 1.0% acetic acid solution, and heated and stirred under 80℃water bath to dissolve, thereby obtaining 0.2% (w/v) chitosan acetic acid solution. Nitrocellulose filter paper is cut to a suitable shape and size to enable insertion into the connecting tube lumen. It was then fully immersed in the chitosan acetic acid solution for a period of time, followed by drying in an oven at 50 ℃. In addition, 10mg glucose oxidase, 0.3mg horseradish peroxidase and 8mM 4-aminoantipyrine were dissolved in 1mL of 0.1M PBS solution at pH 6.0. The mixture solution was taken out by using a pipette and dropped onto nitrocellulose filter paper pretreated with chitosan acetic acid solution, followed by drying in an oven at 35℃for 40 minutes.

(2) Loading: the connecting tube, the vacuum sampling tube and the 3D printing integrally formed microneedle array (patch) and cavity table described in example 2 were prepared, the constructed glucose chromogenic paper chip was loaded into the connecting tube lumen, one end of the connecting tube was nested outside the connecting portion, and the connecting tube was placed in a refrigerator at 4 ℃ for refrigeration before use. When in use, the other end of the hollow connecting pipe is connected into the vacuum sampling pipe.

2. Application of

Glucose solutions of different concentrations were blindly dissolved in 0.1M PBS and agarose powder was added to prepare 1.5% (w/v) agarose gel to simulate human skin tissue.

And pressing the microneedle array patch into the surface of the hydrogel skin tissue model, keeping the pressed state, connecting the other end of the hollow connecting pipe into a vacuum sampling pipe to generate negative pressure, driving tissue fluid to enter the connecting pipe from the hollow microneedle to contact the paper chip, observing the color development reaction change condition of the paper chip in the connecting pipe, and removing the microneedle array patch device from the skin tissue model after the color change is kept stable. And using a mobile phone as a color reaction image acquisition device, extracting the color of the acquired image into a R, G, B value by using Matlab software, comparing the R, G, B value with a standard system, and calculating to obtain the corresponding glucose concentration.

Example 6

1. construction method

(1) Preparing a multi-element color-developing paper chip:

two hydrophilic areas were printed on the same side of Whatman filter paper using a Xerox Color-Qube 8580Color Printer wax-jet Printer. After heating at 90 ℃ for 4 minutes, the paraffin was transformed into a molten state on the surface of the filter paper and penetrated the filter paper, forming a hydrophobic block between the reaction zones. 5mg of lactate oxidase, 0.15mg of horseradish peroxidase and 10mM of o-phenylenediamine were dissolved in 1mL of a 0.2% (w/v) chitosan acetic acid solution, and added dropwise to the hydrophilic region 1 to form a lactic acid detection zone. A mixed solution of 0.36mM bromocresol green, 0.46mM bromocresol purple, and 0.08mM bromophenol blue was added dropwise to hydrophilic zone 2, forming a pH detection zone.

(2) Loading: the connecting tube, the vacuum sampling tube and the single metal hollow microneedle described in example 1 were prepared, the constructed multi-element color-developing paper chip was loaded in the lumen of the connecting tube, one end of the connecting tube was connected to the single metal hollow microneedle, and the paper chip portion was extended into the hollow microneedle cavity. Before use, the mixture is placed in a refrigerator at 4 ℃ for refrigeration.

2. Application of

Agarose powder was added to blinded samples of different pH to prepare 1.5% (w/v) agarose gel which mimics human skin tissue.

The method comprises the steps of penetrating a hollow microneedle into the surface of a hydrogel skin model, connecting the other end of a hollow connecting pipe to a vacuum sampling pipe, driving tissue fluid from the hollow microneedle to the connecting pipe by negative pressure of the vacuum sampling pipe, observing the color reaction change condition of a paper chip in the connecting pipe, and removing the hollow microneedle paper chip device from skin tissues after the color change is kept stable. And using a SONY A72 camera as a color reaction image acquisition device, extracting the color of the acquired image into a R, G, B value by using Python software, comparing the R, G, B value with a standard system, and calculating to obtain a corresponding pH value.

Example 7

1. construction method

(1) Preparation of a multi-paper chip based on color development sensing:

two hydrophilic areas were printed on the front and back sides of nitrocellulose filter paper using a Xerox Color-Qube 8580Color Printer wax-jet Printer. The two hydrophilic areas are arranged in a staggered mode and are respectively arranged at the front end and the rear end of the back face of the filter paper. After heating at 90 ℃ for 4 minutes, the paraffin turned to melt on the surface of the filter paper and penetrated the filter paper, forming a hydrophobic block between the reaction zones. 10mg of glucose oxidase, 0.3mg of horseradish peroxidase and 8mM of 4-aminoantipyrine are dissolved in 1mL of 0.1M PBS solution with pH of 6.0, and the solution is dropwise added into a hydrophilic area 1 at the front end of the front surface of filter paper to form a glucose detection area; 5mg of lactate oxidase, 0.15mg of horseradish peroxidase and 10mM of o-phenylenediamine were dissolved in 1mL of a 0.2% (w/v) chitosan acetic acid solution, and the solution was added dropwise to the hydrophilic region 2 at the rear end of the reverse side of the filter paper to form a lactate detection region.

Example 8

The embodiment provides a construction method and application of a paper chip device, wherein the construction method comprises the following steps:

1. construction method

(1) Preparation of a glucose paper chip based on self-luminous sensing:

the filter paper was immersed in a solution containing 20mM Co ²⁺ In 0.8mM dimethylimidazole, 2mg/mL glucose oxidase, 15mM luminol and 50mM HEPES buffer solution, then placed in a shaker at 30℃for 20 minutes, then dried in vacuo.

2. Application of

The micro-needle array patch is pressed into the surface of the hydrogel skin tissue model, the pressing state is kept, the other end of the hollow connecting pipe is connected into the vacuum sampling pipe to generate negative pressure, tissue fluid is driven to enter the connecting pipe from the hollow micro-needle to contact the paper chip, the self-luminous reaction change condition of the paper chip in the connecting pipe is observed, a mobile phone is used as luminous intensity collecting equipment to shoot, the shot picture is exposed for 60 seconds, the signal is converted into a gray value by using imageJ software, the gray value is compared with a standard system, and the corresponding glucose concentration is calculated.

Example 9

The embodiment provides an application of a paper chip device, which comprises the following steps:

the luteinizing hormone solutions with different concentrations are dissolved in 0.1M PBS solution in blind mode, agarose powder is added, and 1.5% (w/v) agarose gel is prepared to simulate human skin.

The connecting tube, vacuum sampling tube and 3D printing integrally formed microneedle array (patch) and cavity table described in example 2 were prepared, and commercially available luteinizing hormone test strips (paper chips) were cut (1.5 mm wide and 10mm long) and then loaded into the lumen of the connecting tube, and one end of the connecting tube was nested outside the connecting portion. And pressing the microneedle array patch into the surface of the hydrogel skin tissue model, keeping a pressing state, then connecting the other end of the hollow connecting pipe into a vacuum sampling pipe to generate negative pressure, driving tissue fluid to enter the connecting pipe from the hollow microneedle to contact the paper chip, and observing the color development condition of the C line and the T line of the paper chip in the hollow connecting pipe by naked eyes, and obtaining a luteinizing hormone detection result after the color change is kept stable.

Experimental example 1 chromogenic detection and verification of glucose in skin model

The glucose solutions with different concentrations are blind samples, dissolved in 0.1M PBS solution, added with agarose powder, and 8 groups of 1.5% (w/v) agarose gel with different glucose concentrations are prepared to simulate human skin tissues. The test and control methods were used, respectively.

Test group: the paper chip device and the application method of the embodiment 5 of the utility model are adopted to detect the agarose gel simulated human skin tissue, and the content of glucose in the glucose solution blind sample is calculated.

Control group: pressing agarose water gel to simulate human skin tissue, and detecting liquid by using a commercially available blood sugar detector after the liquid flows out.

The results of the test group and the control group were compared in similarity, and the results are shown in FIG. 7, R ² The paper chip device color development sensing system adopted by the utility model is proved to have higher accuracy.

Experimental example 2 paper chip device on-site rapid detection of New Zealand rabbit Living tissue fluid glucose content

New Zealand rabbits (2.5 kg, female) were weighed and fixed on a rabbit holding table, and a solution of sodium pentobarbital physiological saline was prepared at a dose of 1mL/kg, 3%, and a sodium pentobarbital anesthetic was slowly injected along the auricular margin by intravenous injection. After confirming the success of anesthesia, sterilization was performed with iodophor. Depilating on the back side of rabbit ear with depilatory, and wiping with physiological saline.

Tissue fluid of rabbit ear skin was extracted and tested using the paper chip device and application method of example 5 of the present utility model. And (3) using a mobile phone as a color reaction image acquisition device, extracting the color of the acquired image into a R, G, B value by using Matlab software, comparing the R, G, B value with a standard system, and calculating to obtain the corresponding glucose concentration of 5.99mmol/L. After the paper chip device in the embodiment 5 of the utility model is detected, the connecting pipe on the hollow micro-needle patch is taken down, the connecting part of the hollow micro-needle patch is attached to the sample inlet of the detection card of the commercial glucometer, and the residual tissue fluid in the hollow micro-needle patch enters the glucometer detection card through the connecting part to detect that the glucose concentration is 5.99mmol/L. In addition, the rabbit ear vein blood is taken, and the glucose concentration of the rabbit ear vein blood is measured to be 6.00mmol/L by adopting a commercial blood glucose detector, so that the paper chip chromogenic sensing system adopted by the utility model has higher accuracy.

Experimental example 3 paper chip device on-site rapid detection of New Zealand rabbit Living tissue pH content

Tissue fluid of rabbit ear skin was extracted and tested using the paper chip device and application method of example 6 of the present utility model. And using a SONY A72 camera as a color reaction image acquisition device, extracting the color of the acquired image into a R, G, B value by using Python software, comparing the R, G, B value with a standard system, and calculating to obtain the corresponding pH value of 7.40. As the pH value in the healthy rabbit ear subcutaneous tissue liquid is similar to that of the rabbit ear edge venous blood, the pH value of the rabbit ear edge venous blood is 7.40, which is measured by a laboratory standard pH meter, and the paper chip chromogenic sensing system adopted by the utility model is proved to have higher accuracy.

It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the utility model.

Claims

1. The paper chip device is characterized by comprising a connecting pipe and a negative pressure generator, wherein a paper chip is arranged in a lumen of the connecting pipe, one end of the connecting pipe is communicated with a hollow microneedle, the other end of the connecting pipe is communicated with the negative pressure generator during detection, and a pore canal communicated with the connecting pipe is arranged on the hollow microneedle.

2. The paper chip device according to claim 1, wherein a cavity stage is further provided between the connection pipe and the hollow microneedle, a cavity structure is formed inside the cavity stage, a cavity of the cavity stage is communicated with a duct of the hollow microneedle, and the duct of the hollow microneedle is communicated with the connection pipe through the cavity stage.

3. The paper chip device according to claim 2, wherein a connecting portion communicating with a connecting pipe is provided at one side of the cavity stage, and a cavity of the cavity stage communicates with the connecting pipe through the connecting portion.

4. The paper chip device of claim 1, wherein a plurality of tunnels are provided on the hollow microneedles; and/or, the hollow microneedles are arranged in a plurality to form a microneedle array.

5. The paper chip device of claim 2, wherein a support body is disposed within the cavity that connects the top and bottom of the cavity table.

6. The paper chip device of claim 5, wherein the support is disposed away from the opening of the hollow microneedle; and/or the supporting bodies are arranged in parallel with each other or around the center of the cavity; and/or the number of the supporting bodies is 2-4; and/or the support body is provided with a through hole; and/or the supporting bodies are not connected with each other; and/or the support body is not connected with the inner wall in the cavity.

7. The paper chip device of claim 1, wherein the paper chip is loaded in the connecting tube lumen and adjacent to one side of the hollow microneedle; and/or the paper chip is wholly located in the connecting pipe or partly located in the connecting pipe and partly located in the cavity.

8. The paper chip device of claim 1, wherein the paper chip is pre-modified with a chemical sensing system capable of detecting and analyzing tissue fluid components, the response signal of which comprises color development or luminescence.