CN114041831A - Device for detecting osteoporosis treatment effect and preparation method thereof - Google Patents
Device for detecting osteoporosis treatment effect and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a device for detecting osteoporosis treatment effect and a preparation method thereof, wherein the device comprises a hollow micro-needle array unit, a negative pressure cover, a negative pressure pump and a water-absorbing substance; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed, the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, the outer groove is detachably connected with the base, the water-absorbing substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump; a hollow microneedle array for penetrating the skin and serving as a transmission channel for a bone transition marker; the negative pressure cover is used for transmitting the negative pressure of the negative pressure pump, so that the bone conversion marker in the blood is conveniently extravasated and enriched in tissue fluid; a water absorbing substance for storing a bone transition marker. The embodiment of the invention can safely detect the treatment effect of osteoporosis, has low price and high universality, and can be widely applied to the technical field of medical instruments.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a device for detecting osteoporosis treatment effect and a preparation method thereof.
Background
Osteoporosis is a slowly progressing metabolic skeletal disease, primarily characterized by low bone mass and microstructural destructive changes in bone tissue, leading to increased bone fragility and risk of fracture. With the development of the aging of the global population, osteoporosis becomes a public health problem all over the world, brittle fracture of the disease can cause disabled and even death of patients, the life quality of the patients is seriously affected, most patients are known to suffer from the disease after the fracture happens because the disease of the osteoporosis progresses slowly and is difficult to detect, the disease condition reaches a serious degree, and the incidence rate of the fracture is high, so that the significance of early diagnosis, treatment and prevention of the osteoporosis and the osteoporotic fracture is great, and how to achieve the early diagnosis and treatment monitoring by a convenient inspection means is the future development direction of dealing with the osteoporosis.
The bone density value of unit bone area of the current dual-energy X-ray detection is the gold standard for osteoporosis diagnosis, but because the bone structure changes slowly, the short-term treatment effect of the osteoporosis patient cannot be fed back by the bone density detection, so that the treatment effect of diagnosing the osteoporosis by singly adopting the bone density detection is not comprehensive enough. Meanwhile, due to the problem of ray safety, bone density is not suitable for large-scale general investigation and repeated examination. Other osteoporosis detection means include quantitative CT, micro CT, ultrasound and the like, which can detect bone density and bone microstructure, but are not used as a conventional clinical diagnosis method at present and are more suitable for scientific research due to uncertain diagnosis threshold, relatively large radiation dose, high price and the like.
Disclosure of Invention
In view of the above, an object of the embodiments of the present invention is to provide an apparatus for detecting osteoporosis treatment effect and a method for manufacturing the same, which can safely detect osteoporosis treatment effect, and is low in cost and high in universality.
In a first aspect, an embodiment of the present invention provides an apparatus for detecting an osteoporosis treatment effect, including a hollow microneedle array unit, a negative pressure cover, a negative pressure pump, and a water-absorbing substance; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed, the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, the outer groove is detachably connected with the base, the water-absorbing substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump;
the hollow micro-needle array is used for penetrating the skin and serving as a transmission channel of a bone transition marker;
the negative pressure cover is used for transmitting the negative pressure of the negative pressure pump, so that the bone conversion marker in the blood is conveniently extravasated and enriched in tissue fluid;
the water-absorbing material is used for storing the bone transition marker.
Optionally, the microneedle length range of the hollow microneedle array comprises 1100um to 1300 um.
Optionally, the diameter of the microneedle hole of the hollow microneedle array is in a range of 150-250 mm.
Optionally, the outer tank is nestingly connected with the base.
Optionally, the negative pressure interface is connected with the negative pressure pump through a rubber tube.
Optionally, the water-absorbing substance comprises any one of filter paper or gauze.
In a second aspect, embodiments of the present invention provide a method for preparing a device for detecting an effect of a treatment for osteoporosis, including:
preparing a mold of the hollow microneedle array unit; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed;
injecting a fluid material for preparing the hollow microneedle array unit into the mould, and stripping the cured fluid material to obtain the hollow microneedle array unit;
preparing a negative pressure cover, wherein the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, and the size of the outer groove is matched with that of the base;
providing a negative pressure pump and a water-absorbing substance;
assembling the hollow microneedle array unit, the negative pressure cover, the negative pressure pump and the water-absorbent substance, wherein the water-absorbent substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump.
Optionally, the mold is prepared by:
mixing polydimethylsiloxane and a curing agent according to a preset proportion and fully stirring;
placing the uncured mixed solution in a preset vacuum environment for a preset time;
and casting the mixed solution on a preset SU-8 template and drying to form the mold.
Optionally, the injecting the fluid material for preparing the hollow microneedle array unit into the mold, and peeling off the cured fluid material to obtain the hollow microneedle array unit specifically includes:
heating polymethyl methacrylate powder to a molten state at a preset temperature;
casting the material in the molten state into the mold and allowing the material in the molten state to solidify for a period of time;
the solidified material was peeled off the mold and a through hole was drilled in the middle position of each microneedle by laser.
The implementation of the embodiment of the invention has the following beneficial effects: the device in the embodiment comprises a hollow micro-needle array unit, a negative pressure cover, a negative pressure pump and a water-absorbing substance, wherein the hollow micro-needle array unit penetrates through the skin, the negative pressure pump enables the subcutaneous part to form a negative pressure state so as to enable the bone transformation marker to be enriched in tissue fluid and convenient to rapidly extract, and the bone transformation marker is stored in the water-absorbing substance through a hollow micro-needle array channel and used for detection, so that the osteoporosis treatment effect is safely detected, and the device is low in price and high in universality.
Drawings
Fig. 1 is a schematic structural diagram of a hollow microneedle array unit and a negative pressure cover in an apparatus for detecting osteoporosis treatment effect according to an embodiment of the present invention;
FIG. 2 is a pictorial view of an apparatus for detecting the effectiveness of a treatment for osteoporosis in accordance with an embodiment of the present invention;
FIG. 3 is a graph showing the results of extracting fluorescence intensities of three fluorescent mimics with different sizes in interstitial fluid and three fluorescent mimics with different sizes in plasma by using a non-negative pressure method and a negative pressure method according to an embodiment of the present invention;
FIG. 4 is a graph showing the correlation between three fluorescent mimics of different sizes extracted from interstitial fluid by non-negative pressure method and three fluorescent mimics of different sizes in plasma according to an embodiment of the present invention;
FIG. 5 is a graph comparing the concentration of a bone turnover marker in plasma and a bone turnover marker extracted by non-negative pressure method and negative pressure method according to an embodiment of the present invention;
FIG. 6 is a graph showing the correlation between bone turnover markers extracted by non-negative pressure method and bone turnover markers in plasma according to an embodiment of the present invention;
fig. 7 is a flowchart illustrating steps of a method for manufacturing a device for detecting an effect of osteoporosis treatment according to an embodiment of the present invention.
Detailed Description
The invention is described in further detail below with reference to the figures and the specific embodiments. The step numbers in the following embodiments are provided only for convenience of illustration, the order between the steps is not limited at all, and the execution order of each step in the embodiments can be adapted according to the understanding of those skilled in the art.
The detection of the information of the biological molecules can provide a powerful method for analyzing the mechanism of life activities, and detection objects can be arranged on various layers from cells, tissues, organs to organisms and the like, and cover various biological molecules, including macromolecular substances such as DNA, protein, hormone and the like. The biomarker is an indicator which can be used for judging in the physiological state and the disease occurrence process, can be applied to the diagnosis of diseases, the combing and judging of the disease process, the evaluation of the clinical effectiveness and the safety of treatment schemes and new drugs, and can be used for more accurately and quickly diagnosing and judging the disease condition by cooperatively using the biomarker and a detection method in clinical medicine. Bone metabolism is a process of old bone resorption and new bone remodeling, which can be reflected in real time by bone turnover markers. Bone turnover markers are classified into bone formation markers (type I procollagen amino-terminal propeptide (PINP), bone-specific alkaline phosphatase, osteoprotegerin, etc.) and bone resorption markers (type I collagen-crosslinked carboxy-terminal peptide (CTX-I), tartrate-resistant acid phosphatase, etc.). Because of their high sensitivity and specificity in serum, PINP and CTX-I have been recommended by the International Osteoporosis Foundation (IOF) and the International Union of clinical chemistry (IFCC) as reference indicators for monitoring bone metabolism. With the aid of PINP and CTX-I, physicians can effectively monitor the early effects of osteoporosis treatment and adjust the treatment regimen in time to prevent osteoporotic fractures that may occur in the future.
The amount of a small molecule biomarker in the subcutaneous tissue Fluid (ISF) of a human is closely related to the concentration of the corresponding small molecule biomarker in the blood. Based on the correlation, the concentration of the corresponding biomarker in blood can be inferred by detecting the concentration of the small molecular biomarker in subcutaneous tissue fluid. Macromolecular biomarkers are usually present only in blood vessels and are difficult to extravasate across the vessel wall into interstitial fluid. On the other hand, due to the miniaturized design of the needle head of the microneedle, the microneedle avoids pain or bleeding caused by puncturing blood vessels, and the feasibility of directly detecting macromolecular biomarkers from blood by the microneedle is also limited. And if the length of the microneedle needle is increased to puncture the subcutaneous blood vessel, the microneedle needle is similar to a common metal needle, and is easy to cause pain, bleeding and infection risks. Thus, macromolecular biomarkers remain difficult to extract and detect using microneedle array technology. However, many important biomarkers have large molecular weights and different chemical properties, such as PINP (molecular weight about 35kDa) among the bone turnover markers, which may bind to plasma proteins and have difficulty penetrating the capillary wall.
As shown in fig. 1, an embodiment of the present invention provides an apparatus for detecting an osteoporosis treatment effect, including a hollow microneedle array unit (a-1 is a top view, a-2 is a side view), a negative pressure cap c, a negative pressure pump, and a water-absorbing substance b; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed, the negative pressure cover c comprises an outer groove c-1, an inner groove c-2 and a negative pressure port c-3, the outer groove c-1 is detachably connected with the base, the water-absorbing substance b is arranged in the inner groove c-2, and the negative pressure port c-3 is connected with the negative pressure pump;
the hollow micro-needle array is used for penetrating the skin and serving as a transmission channel of a bone transition marker;
the negative pressure cover c is used for transmitting the negative pressure of the negative pressure pump, so that the bone conversion marker in the blood is conveniently extravasated and enriched in tissue fluid;
the water-absorbing material b is used for storing the bone conversion marker.
Referring to fig. 2, fig. 2 is a diagram of an apparatus for detecting an osteoporosis treatment effect, in which fig. 2-a illustrates a hollow microneedle array unit, fig. 2-B and 2-C illustrate a negative pressure cap, fig. 2-D illustrates a module in which the hollow microneedle array unit and the negative pressure cap are assembled, fig. 2-E and 2-F illustrate a top view and a side view of microneedles under a scanning electron microscope, respectively, a scale 2000um of fig. 2-a to 2-D, and a scale 200um of fig. 2-E to 2-F. In fig. 2-B and 2-C, the black squares represent negative pressure ports connected to a negative pressure pump, the black circles represent outer grooves in which microneedle arrays are placed, and the black triangles represent inner grooves in which absorbent materials are stored.
Optionally, the microneedle length range of the hollow microneedle array comprises 1100um to 1300 um.
It should be noted that the length of the microneedle in this embodiment is set to 1200um, so that the microneedle can penetrate the subcutaneous tissue and does not touch the blood vessels and nerves in the dermis.
Optionally, the diameter of the microneedle hole of the hollow microneedle array is in a range of 150-250 mm.
It should be noted that, the diameter of the hollow microneedle array in this embodiment is set to 200mm, which can generate effective capillary force to draw and extract tissue fluid, or quickly extract sufficient tissue fluid under the cooperation of negative pressure.
Optionally, the outer tank is nestingly connected with the base.
It should be noted that, because the outer trough and the base are made of hard materials and the sizes of the outer trough and the base are matched with each other, the outer trough and the base are connected in a nested manner, so that the installation is convenient. The connection mode of the outer groove and the base is various, and the embodiment is not limited in particular.
Optionally, the negative pressure interface is connected with the negative pressure pump through a rubber tube.
It should be noted that the negative pressure interface and the negative pressure pump are connected through a rubber tube to form good sealing performance, which is convenient for rapidly realizing the negative pressure requirement.
Optionally, the water-absorbing substance comprises any one of filter paper or gauze.
It should be noted that the water-absorbing substance includes, but is not limited to, filter paper or gauze, and may be capable of adsorbing and storing the marker in the tissue fluid, and this embodiment is not particularly limited.
The implementation of the embodiment of the invention has the following beneficial effects: the device in the embodiment comprises a hollow micro-needle array unit, a negative pressure cover, a negative pressure pump and a water-absorbing substance, wherein the hollow micro-needle array unit penetrates through the skin, the negative pressure pump enables the subcutaneous part to form a negative pressure state so as to enable the bone transformation marker to be enriched in tissue fluid and convenient to rapidly extract, and the bone transformation marker is stored in the water-absorbing substance through a hollow micro-needle array channel and used for detection, so that the osteoporosis treatment effect is safely detected, and the device is low in price and high in universality. In addition, the device for detecting the osteoporosis treatment effect in the embodiment has the advantages of compact structure, convenience in use, small wound, no pain and high tissue fluid extraction efficiency.
Example one
This example demonstrates the extraction effect of a device with a negative pressure unit in interstitial fluid.
Three fluorescent substances with different molecular weights, rhodamine B (molecular weight: 479Da), Cy5-dextran (molecular weight: 5kDa) and FITC-dextran (molecular weight: 40kDa) were selected, and their efficiency of detection through the capillary wall into the tissue fluid was evaluated by a hollow microneedle system under a non-negative pressure method and a negative pressure method, respectively. The specific implementation mode is as follows: the three fluorescent mimics are respectively injected into a mouse body through veins, subcutaneous tissue fluid on the back of the mouse is collected by adopting a non-negative pressure method and a negative pressure method, and simultaneously, blood plasma of the mouse is collected, and the fluorescence intensity of fluorescent substances in the tissue fluid and the blood plasma and the linear correlation between the fluorescent substances are compared. Non-negative pressure method: the hollow microneedle extraction system is used for extracting tissue fluid by means of the capillary force of microneedles. A negative pressure method: under the assistance of a negative pressure vacuum pump, the tissue fluid is extracted by a hollow microneedle extraction system by utilizing negative pressure (-50kPa) and the capillary force of the microneedles. The experimental results are shown in fig. 3 and 4.
Quantitatively analyzing the fluorescence intensity of three fluorescence mimics with different sizes in interstitial fluid (extracted by a non-vacuum method or a vacuum method) and plasma, wherein the fluorescence intensity is in direct proportion to the amount of the substance. As can be seen from FIG. 3, the results of the non-negative pressure method and the negative pressure method were not statistically different for the substances with smaller molecular weights (rhodomine B and Cy5-dextran), whereas the negative pressure method enriched the fluorescence intensity in the tissue fluid higher for the large molecule FITC-dextran. Data are presented as mean ± standard deviation, n-12 replicates. Significance was calculated by one-way anova, # p <0.05, # p < 0.01.
Correlation of fluorescent substances between interstitial fluid (extracted by non-negative pressure method or negative pressure method) and plasma. Fig. 4 shows the correlation between the fluorescence intensity in the tissue fluid and the plasma sample of the rhodamine B pair (non-negative pressure method: R2 ═ 0.63, R ═ 0.79, P ═ 0.002; negative pressure method: R2 ═ 0.73, R ═ 0.86, P <0.001, pierce correlation coefficient test), Cy5-dextran (non-negative pressure method: R2 ═ 0.65, R ═ 0.80, P ═ 0.002; negative pressure method: R2 ═ 0.73, R ═ 0.85, P < 0.001), and FITC-dextran (non-negative pressure method: R2 ═ 0.36, R ═ 0.60, P ═ 0.038; negative pressure method: R2 ═ 0.64, R ═ 0.80, P ═ 0.002).
As can be seen from fig. 3 and 4, the negative pressure cooperative microneedle diagnosis device can effectively promote the macromolecular substances in blood to permeate through the capillary wall and enter into the tissue fluid, and increase the concentration of the macromolecular substances in the tissue fluid, compared with a non-negative pressure microneedle device.
Example two
This example demonstrates the application of a device with a negative pressure unit to the detection of the therapeutic effect of osteoporosis.
A non-negative pressure method and a negative pressure method are respectively applied to continuously extracting and monitoring bone transformation markers PINP and CTX-I in tissue fluid in an osteoporosis mouse model, and concentration comparison and correlation analysis are carried out on the bone transformation markers PINP and CTX-I in plasma, so that the treatment effect of osteoporosis in real time in the tissue fluid is monitored.
The specific implementation mode is as follows: selecting 12-week-old C57bl/6 mice, and dividing the mouse model into a control group (non-osteoporosis group) and an osteoporosis group (8 mice/group); two groups of mice were subjected to sham surgery and ovariectomy, and the relative concentrations of PINP (molecular weight of about 35kDa) and CTX-I (molecular weight of about 1000Da) in tissue fluid and plasma were measured at 0 week, 6 weeks, 9 weeks and 12 weeks, respectively, and the correlation therebetween was analyzed. The osteoporosis group was given an intravenous anti-osteoporosis zoledronic acid treatment at week 6, and the control group was given the same dose of physiological saline. The experimental results are shown in fig. 5 to 6.
Comparison of the concentrations of PINP and CTX-I in interstitial fluid (non-negative pressure and negative pressure extraction) and plasma in the mouse model. As shown in fig. 5, in the results of the small molecule CTX-I, the concentration of the non-negative pressure method and the negative pressure method in the control group and the osteoporosis group varied in the same manner as in the plasma; in contrast, in the case of macromolecular PINP, only the negative pressure method produced concentration changes in the control group and the osteoporosis group consistent with those in plasma. Data are presented as mean ± standard deviation, n ═ 8 replicates. Statistical significance was calculated by unpaired t-test, # p <0.05, # p <0.01, # p < 0.001.
Correlation between CTX-I and PINP (non-negative pressure and negative pressure extraction) in interstitial fluid and plasma concentration. As can be seen from fig. 6, the correlation between a and B paired plasma and interstitial fluid: CTX-I (non-negative pressure method: R)2＝0.72，r＝0.85，P<0.001; a negative pressure method: r2＝0.91，r＝0.95，P<0.001, pearson correlation coefficient test) and PINP (non-negative pressure method: r2＝0.53， r＝0.73，P<0.001; a negative pressure method: r2＝0.85，r＝0.92，P<0.001)，n＝64。
As can be seen from FIGS. 5 and 6, although PINP and CTX-I can be monitored in interstitial fluid by non-negative pressure method, the negative pressure method significantly increases the concentration of PINP and CTX-I in interstitial fluid and improves their correlation with plasma, especially in macromolecules, which indicates that more accurate monitoring results can be obtained by the application of negative pressure in conjunction with the microneedle diagnostic device.
As shown in fig. 7, an embodiment of the present invention provides a method for manufacturing a device for detecting an effect of osteoporosis treatment, including:
s100, preparing a mold of the hollow microneedle array unit; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed.
Optionally, the mold is prepared by:
s110, mixing polydimethylsiloxane and a curing agent according to a preset proportion and fully stirring;
s120, placing the uncured mixed solution in a preset vacuum environment for a preset time;
and S130, casting the mixed solution on a preset SU-8 template, and drying to form the mold.
Specifically, Polydimethylsiloxane (PDMS) and a curing agent were mixed in a ratio of 10:1 and sufficiently stirred; placing the uncured mixed solution in a vacuum environment of 4.5PA for 30 minutes to remove air bubbles; the PDMS solution was cast onto a photolithographically customized SU-8 template and then dried overnight at 60 ℃ to form a PDMS mold.
S200, injecting the fluid material for preparing the hollow microneedle array unit into the mould, and stripping the cured fluid material to obtain the hollow microneedle array unit.
Optionally, the injecting the fluid material for preparing the hollow microneedle array unit into the mold, and peeling off the cured fluid material to obtain the hollow microneedle array unit specifically includes:
s210, heating polymethyl methacrylate powder to a molten state at a preset temperature;
s220, casting the material in the molten state into the mold, and standing for a plurality of times to solidify the material in the molten state;
and S230, stripping the solidified substance from the mold, and drilling a through hole in the middle section of each microneedle by using laser.
Specifically, Polymethylmethacrylate (PMMA) powder (molecular weight: 75000Da) was heated to a molten state at 200 ℃, and then cast into a PDMS mold; after being placed in vacuum for 5 hours, the microneedle array is cured in a PDMS mold and then peeled off from the mold; the laser-beam drilling machine inputs 800W of power and 0.25 second/hole working time, and each micro-needle drills a 200mm through hole.
S300, preparing a negative pressure cover, wherein the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, and the size of the outer groove is matched with that of the base.
Specifically, the negative gland is designed according to the size matched with the hollow microneedle array and is processed and manufactured on a PMMA plate by using a precision engraving machine; wherein, milling cutter diameter 1mm, rotational speed 8000rpm, machining precision 20 um.
S400, providing a negative pressure pump and a water-absorbing substance.
Specifically, the water-absorbent substance may be ordinary filter paper or gauze.
S500, assembling the hollow microneedle array unit, the negative pressure cover, the negative pressure pump and the water-absorbing substance, wherein the water-absorbing substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump.
Specifically, firstly, a water-absorbing substance is placed in an inner groove of a negative pressure cover, then the hollow microneedle array unit is connected with an outer groove of the negative pressure cover in a nested manner, and finally, a negative pressure interface is connected with a negative pressure pump through a rubber tube.
The implementation of the embodiment of the invention has the following beneficial effects: the device in the embodiment comprises a hollow micro-needle array unit, a negative pressure cover, a negative pressure pump and a water-absorbing substance, wherein the hollow micro-needle array unit penetrates through the skin, the negative pressure pump enables the subcutaneous part to form a negative pressure state so as to enable the bone transformation marker to be enriched in tissue fluid and convenient to rapidly extract, and the bone transformation marker is stored in the water-absorbing substance through a hollow micro-needle array channel and used for detection, so that the osteoporosis treatment effect is safely detected, and the device is low in price and high in universality. In addition, the device for detecting the osteoporosis treatment effect in the embodiment has the advantages of compact structure, convenience in use, small wound, no pain and high tissue fluid extraction efficiency.
While the preferred embodiments of the present invention have been illustrated and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (9)
1. A device for detecting osteoporosis treatment effect is characterized by comprising a hollow micro-needle array unit, a negative pressure cover, a negative pressure pump and a water-absorbing substance; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed, the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, the outer groove is detachably connected with the base, the water-absorbing substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump;
the hollow micro-needle array is used for penetrating the skin and serving as a transmission channel of a bone transition marker;
the negative pressure cover is used for transmitting the negative pressure of the negative pressure pump, so that the bone conversion marker in the blood is conveniently extravasated and enriched in tissue fluid;
the water-absorbing material is used for storing the bone transition marker.
2. The apparatus of claim 1, wherein the hollow microneedle array has a microneedle length ranging from 1100um to 1300 um.
3. The device of claim 1, wherein the hollow microneedle array has a microneedle aperture size ranging from 150 to 250 mm.
4. The device of any one of claims 1-3, wherein the outer channel is nestably coupled to the base.
5. The device of any one of claims 1-3, wherein the negative pressure port is connected to the negative pressure pump via a hose.
6. The device according to any one of claims 1-3, wherein the water-absorbent substance comprises any one of filter paper or gauze.
7. A method of making a device for detecting the effectiveness of a treatment for osteoporosis, comprising:
preparing a mold of the hollow microneedle array unit; the hollow microneedle array unit comprises a hollow microneedle array and a base which are integrally formed;
injecting a fluid material for preparing the hollow microneedle array unit into the mould, and stripping the cured fluid material to obtain the hollow microneedle array unit;
preparing a negative pressure cover, wherein the negative pressure cover comprises an outer groove, an inner groove and a negative pressure interface, and the size of the outer groove is matched with that of the base;
providing a negative pressure pump and a water-absorbing substance;
assembling the hollow microneedle array unit, the negative pressure cover, the negative pressure pump and the water-absorbent substance, wherein the water-absorbent substance is arranged in the inner groove, and the negative pressure interface is connected with the negative pressure pump.
8. The method of claim 7, wherein the mold is prepared by:
mixing polydimethylsiloxane and a curing agent according to a preset proportion and fully stirring;
placing the uncured mixed solution in a preset vacuum environment for a preset time;
and casting the mixed solution on a preset SU-8 template and drying to form the mold.
9. The method according to claim 8, wherein the injecting the fluid material for preparing the hollow microneedle array unit into the mold, and peeling off the solidified fluid material to obtain the hollow microneedle array unit specifically comprises:
heating polymethyl methacrylate powder to a molten state at a preset temperature;
casting the material in the molten state into the mold and allowing the material in the molten state to solidify for a period of time;
the solidified material was peeled off the mold and a through hole was drilled in the middle position of each microneedle by laser.
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| US7344499B1 (en) * | 1998-06-10 | 2008-03-18 | Georgia Tech Research Corporation | Microneedle device for extraction and sensing of bodily fluids |
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