Microneedle equipment for subcutaneous tissue interstitial fluid extraction and sampling method

Abstract

The invention relates to a microneedle device for subcutaneous tissue interstitial fluid extraction and a sampling method, and belongs to the technical field of tissue interstitial fluid extraction.The microneedle device comprises a fixator body, the fixator body comprises an upper fixator and a lower fixator, the two sides of the upper fixator are connected with the two sides of the lower fixator through elastic pieces, and an array channel is formed in the upper fixator; the pressure detection head comprises a pressure detection shell and a sheet-shaped dynamometer probe, a hollow column assembly matched with the array channel is arranged at the bottom of the pressure detection shell, the hollow column assembly comprises a plurality of hollow columns, columns are arranged in the hollow columns in a matched mode, and a containing groove is formed in the pressure detection shell; the microneedle array structure comprises a microneedle structure shell, a capillary tube and a microneedle, a tube body matched with the array channel is arranged at the bottom of the microneedle structure shell, a mounting hole is formed in the tube body, the capillary tube is arranged in the mounting hole, the microneedle is arranged at the bottom of the tube body, and the microneedle is communicated with the capillary tube.

Description

Technical Field

[0001] This invention relates to the field of interstitial fluid extraction technology, and in particular to a microneedle device and sampling method for extracting subcutaneous interstitial fluid. Background Technology

[0002] Subcutaneous interstitial fluid (ISF) contains various proteins, genetic material, and metabolites, making it an important biological sample for assessing local physiological status. Traditional detection methods, namely blood tests, are insufficient to reflect the local pathophysiological condition, causing difficulties in disease assessment, intervention efficacy, and medication guidance.

[0003] However, traditional collection methods (such as microdialysis, vesicle aspiration, or single hollow microneedles) have many shortcomings: first, the procedures are highly invasive, requiring local anesthesia and a long recovery period; second, the collection efficiency is low, typically requiring one hour or more to collect even a small amount of fluid; and third, the external devices are complex, limiting their clinical and routine monitoring applications. Due to the low efficiency and significant discomfort of existing methods, most studies on interstitial fluid to date have been limited to small groups of subjects, making it difficult to support large-scale studies. Summary of the Invention

[0004] In order to overcome the above-mentioned defects of the prior art, the present invention provides a microneedle device and sampling method for extracting subcutaneous interstitial fluid, so as to solve the problems mentioned in the background art.

[0005] To achieve the above-mentioned objectives, the present invention provides a microneedle device for extracting subcutaneous interstitial fluid, comprising: The fixation body includes an upper fixation and a lower fixation. The two sides of the upper fixation are connected to the two sides of the lower fixation by elastic elements. The upper fixation is provided with an array channel. A pressure probe includes a pressure probe housing and a plate-shaped force gauge probe. The bottom of the pressure probe housing is provided with a hollow column assembly that cooperates with the array channel. The hollow column assembly includes a plurality of hollow columns, and a column is provided in the hollow column. The pressure probe housing is provided with a placement slot for placing the plate-shaped force gauge probe. A microneedle array structure includes a microneedle structure housing, a capillary, and microneedles. The bottom of the microneedle structure housing is provided with a tube that mates with the array channel. The tube is provided with a mounting hole. The capillary is disposed in the mounting hole. The bottom of the tube is provided with microneedles, and the microneedles are connected to the capillary.

[0006] Furthermore, the fixator body, the pressure detection housing, the hollow column assembly, and the microneedle structure housing are all made of medical photocurable resin.

[0007] Furthermore, the microneedle is made of 304 stainless steel, one end of the microneedle is a conical hollow with a diameter of 300µm, the other end of the microneedle is a blunt tip connected to a capillary, and the needle length of the microneedle is in the range of 0.3-1.5mm.

[0008] Furthermore, the lower fixator includes a groove for placing and restricting the arm to be collected.

[0009] Another aspect of the present invention provides a method for collecting data using the aforementioned microneedle device, the method comprising: During operation, first clean the target skin area and then install the fixator body; Then, insert the pressure probe through the hole in the fixation device body and press it vertically onto the skin. After installing both, adjust the pressure to the target value, and then remove the pressure probe from the fixation device body. Keeping the fixator body stationary, the microneedle array structure with capillary tubes installed is inserted through the hole of the fixator and installed on the fixator body. The interstitial fluid is driven to the microneedle tip by the spatial pressure gradient formed between the skin tissue and the fixator body, and the interstitial fluid is absorbed into it by the capillary principle. After holding for 10-15 minutes, remove the microneedle array structure for subsequent testing; Data processing and contamination control are required. The collected interstitial fluid needs to be stored at low temperatures and centrifuged before testing to remove any red blood cells and other tissue debris that may be mixed in.

[0010] Furthermore, the target pressure value is 200-500 Newtons per probe.

[0011] Furthermore, the cryopreservation temperature is 2-4 degrees Celsius.

[0012] Compared with the prior art, the beneficial effects of the present invention are: High-efficiency collection: The microneedle array of the microneedle device forms multiple micropores on the skin. By applying external pressure, a spatial pressure gradient is generated, which allows the interstitial fluid to flow out rapidly within 10 minutes. The collection volume can reach 10-15uL, which is 5-10 times higher than the traditional method. Easy to operate: Microneedle devices do not require external power or external equipment such as vacuum pumps or microdialysis pumps, making them suitable for clinical or home self-collection.

[0013] Minimally invasive and comfortable: Microneedles have a small puncture depth, causing minimal damage to the skin, low pain, and rapid skin recovery, making them suitable for repeated sampling and continuous monitoring.

[0014] Highly scalable: The structural parameters can be adjusted according to the target analyte to meet the testing needs of different indications. Attached Figure Description

[0015] Figure 1 This is a three-dimensional structural diagram of the connection between the upper and lower fixators of the present invention; Figure 2 This is an exploded structural diagram of the connection between the pressure probe and the upper fixing device of the present invention; Figure 3 This is a schematic diagram of the main structure of the upper fixator of the present invention; Figure 4 This is a top view of the fixture structure of the present invention; Figure 5 This is a three-dimensional structural diagram of the microneedle array structure of the present invention; Figure 6 This is another three-dimensional structural diagram of the microneedle array structure of the present invention. Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the invention, but not all embodiments. The embodiments of the present invention are described below with reference to the accompanying drawings.

[0017] refer to Figures 1-6 A microneedle device for extracting subcutaneous interstitial fluid, comprising: The main body of the fixation device includes an upper fixation device 1 and a lower fixation device 2. The two sides of the upper fixation device 1 and the two sides of the lower fixation device 2 are respectively connected by elastic elements 3. The upper fixation device 1 is provided with an array channel 4. Specifically, the upper fixator 1 and the lower fixator 2 are connected by elastic elements 3 on both sides. The elastic elements 3 can be rubber bands. The upper fixator 1 also includes upper positioning holes 5 for installing and connecting the elastic elements 3. Two upper positioning holes 5 are provided on one side of the upper fixator 1 and two upper positioning holes 5 are also provided on the other side. Correspondingly, two connecting rods 6 are provided on both sides of the lower fixator 2. The connecting rods 6 are provided with lower holes for passing through the elastic elements 3. The array channel 4 includes four support rods 9 located at the bottom of the upper fixator 1 and four through holes 10. The four through holes 10 pass through the four support rods 9 respectively, so as to allow the microneedle array structure and pressure probe to pass through and contact the skin to be collected. The pressure probe includes a pressure probe housing 13 and a plate-shaped force gauge probe. The bottom of the pressure probe housing 13 is provided with a hollow column assembly that cooperates with the array channel 4. The hollow column assembly includes a plurality of hollow columns 14, and a column 15 is provided in the hollow column 14. The pressure probe housing 13 is provided with a placement slot 16 for placing the plate-shaped force gauge probe. Specifically, the hollow column assembly can consist of four hollow columns 14, and correspondingly four columns 15. The four hollow columns 14 are inserted into the array channel 4, and then the columns 15 are inserted into the hollow columns 14 from the bottom. The plate force gauge probe is installed into the placement slot 16, so that the top of the column 15 contacts the plate force gauge probe. The pressure probe is fixed as a whole by the probe head fixing frame, and the upper fixing device 1 is connected to the lower fixing device 2. The bottom of the column 15 contacts the skin for pressure testing. After the pressure is adjusted to the required value by the elastic element 3, the pressure probe is removed and the microneedle array structure is operated for sampling. The probe head fixing frame includes a side plate 11, and two fixing rods 12 are provided on the side wall of the side plate 11. Correspondingly, the upper fixing device 1 includes a symmetrically arranged positioning plate 7, and the positioning plate 7 is provided with two limiting holes 8 that cooperate with the two fixing rods 12. The microneedle array structure includes a microneedle structure housing 17, a capillary tube, and microneedles 19. The bottom of the microneedle structure housing 17 is provided with a tube body 18 that cooperates with the array channel 4. The tube body 18 is provided with a mounting hole 20. The capillary tube is disposed in the mounting hole 20. The bottom of the tube body 18 is provided with microneedles 19, and the microneedles 19 are connected to the capillary tube. Specifically, the microneedle array structure can be installed on the upper fixator 1 for sampling. After the microneedles 19 contact the skin, the sample is sent to the capillary.

[0018] In some embodiments, the fixator body, pressure detection housing 13, hollow column assembly, and microneedle structure housing 17 are all made of medical photocurable resin, which is relatively simple to mold and can meet the requirements of use.

[0019] In some embodiments, the microneedle 19 is made of 304 stainless steel. One end of the microneedle 19 is a conical hollow with a diameter of 300µm, and the other end of the microneedle 19 is a blunt tip connected to a capillary. The needle length of the microneedle 19 is in the range of 0.3-1.5 mm. Specifically, sampling is performed by contacting the skin through the conical hollow section of the microneedle 19, and the sample is collected through the capillary after sampling.

[0020] In some embodiments, the lower fixator 2 includes a groove 21 for placing and restricting the arm to be sampled. The groove 21 is used to place the arm to be sampled. After the arm is placed, the upper fixator 1 and the lower fixator 2 are fixed. After adjusting the pressure, sampling can be performed.

[0021] A method for collecting samples using the aforementioned microneedle device includes the following steps: During operation, first clean the target skin area. For example, if the collection location is the skin area on the arm, after cleaning, insert the arm into the groove 21 and then install the fixator body, that is, install the arm on the upper fixator 1 and the lower fixator 2. Then, insert the pressure probe through the hole in the fixation device body and press it vertically onto the skin. Install the two using the probe holder, adjust the pressure to the target value, and then remove the pressure probe from the fixation device body. Keeping the fixator body stationary, the microneedle array structure with capillary tubes installed is inserted through the hole of the fixator and installed on the fixator body. The interstitial fluid is driven to the microneedle 19 needle tip by the spatial pressure gradient formed between the skin tissue and the fixator body, and the interstitial fluid is absorbed into the capillary tubes therein by the capillary principle. After holding the microneedle array structure for 10-15 minutes, remove it for subsequent testing. Specifically, you can hold it for 10 or 15 minutes and then remove it to complete the sampling. Data processing and contamination control are required. The collected interstitial fluid needs to be stored at low temperatures and centrifuged before testing to remove any red blood cells and other tissue debris that may be mixed in.

[0022] In some embodiments, the target pressure value is 200-500 Newtons / probe, specifically, the target pressure value can be 200 Newtons / probe or 500 Newtons / probe.

[0023] In some embodiments, the cryopreservation temperature is 2-4 degrees Celsius, specifically, the cryopreservation temperature is 2 degrees Celsius or 4 degrees Celsius.

[0024] Compared with the prior art, this application has the following advantages: High-efficiency collection: The microneedle array of the microneedle device forms multiple micropores on the skin. By applying external pressure, a spatial pressure gradient is generated, which allows the interstitial fluid to flow out rapidly within 10 minutes. The collection volume can reach 10-15uL, which is 5-10 times higher than the traditional method. Easy to operate: Microneedle devices do not require external power or external equipment such as vacuum pumps or microdialysis pumps, making them suitable for clinical or home self-collection.

[0025] Minimally invasive and comfortable: The microneedle 19 has a small puncture depth, causes minimal damage to the skin, has low pain, and allows for rapid skin recovery, making it suitable for repeated sampling and continuous monitoring.

[0026] Highly scalable: The structural parameters can be adjusted according to the target analyte to meet the testing needs of different indications.

[0027] The technical solution of the present invention has been described above in conjunction with specific embodiments. However, it should be noted that the above descriptions are only for explaining the solution of the present invention and should not be construed as a specific limitation on the scope of protection of the invention in any way. Based on this explanation, those skilled in the art can conceive of other specific embodiments or equivalent substitutions of the present invention without creative effort, and all such embodiments or substitutions will fall within the scope of protection of the present invention.

Claims

1. A microneedle device for subcutaneous interstitial fluid extraction, characterized by, The device comprises: a fixator body, which comprises an upper fixator and a lower fixator, the two sides of the upper fixator are connected to the two sides of the lower fixator by elastic members, and the upper fixator is provided with an array channel; a pressure detection head, which comprises a pressure detection shell and a sheet-shaped force gauge probe, the bottom of the pressure detection shell is provided with a hollow column assembly matched with the array channel, the hollow column assembly comprises a plurality of hollow columns, a column is matched in the hollow column, and the pressure detection shell is provided with a placement groove for placing the sheet-shaped force gauge probe; a microneedle array structure, which comprises a microneedle structure shell, a capillary tube and microneedles, the bottom of the microneedle structure shell is provided with a tube body matched with the array channel, the tube body is provided with a mounting hole, the capillary tube is arranged in the mounting hole, and the bottom of the tube body is provided with microneedles, which are in communication with the capillary tube.

2. The microneedle device for subcutaneous interstitial fluid extraction of claim 1, wherein, The fixator body, the pressure detection shell, the hollow column assembly and the microneedle structure shell are all made of medical light-cured resin.

3. The microneedle device for subcutaneous interstitial fluid extraction of claim 1, wherein, The microneedles are made of 304 stainless steel, one end of the microneedle is a tapered hollow with a diameter of 300 µm, the other end of the microneedle is a blunt head connected to the capillary tube, and the needle length of the microneedle is in the range of 0.3-1.5 mm.

4. The microneedle device for subcutaneous interstitial fluid extraction of claim 1, wherein, The lower fixator comprises a groove for placing a restriction arm to be collected.

5. A collection method using the microneedle device for subcutaneous interstitial fluid extraction according to any one of claims 1 to 4, characterized by, The collection method comprises: During operation, first clean the target skin area and install the fixator body; then pass the pressure detection head through the hole of the fixator body and press it vertically on the skin, after the installation of the two, adjust the pressure to the target value, and then remove the pressure detection head from the fixator body; keep the fixator body stationary, and pass the microneedle array structure with the capillary tube installed into the hole of the fixator and install it on the fixator body, use the space pressure gradient formed between the skin tissue and the fixator body to drive the interstitial fluid to the microneedle needle head, and use the capillary principle to absorb the interstitial fluid therein; after keeping for 10-15 minutes, remove the microneedle array structure and perform subsequent detection; data processing and pollution control, the collected interstitial fluid needs to be stored at low temperature, and red blood cells and other tissue fragments that may be mixed need to be removed by centrifugation before detection.

6. The method of claim 4, wherein, The target value of the pressure is 200-500 Newton / probe.

7. The method of claim 4, wherein, The temperature of the low-temperature storage is 2-4 degrees Celsius.

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