An electronic patch for hematoma drainage detection and a preparation method thereof
By designing an electronic patch for hematoma drainage detection, employing a microneedle and drainage layer structure, and combining graphene sensitive materials and sensor detectors, painless autonomous drainage and detection of multiple biomarkers are achieved, solving the problem of pain associated with neonatal scalp hematoma drainage devices and providing effective disease screening.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HARBIN INST OF TECH
- Filing Date
- 2025-11-24
- Publication Date
- 2026-07-21
AI Technical Summary
Existing neonatal scalp hematoma drainage devices cause pain to newborns and cannot effectively utilize the physiological information in the blood.
An electronic patch for detecting hematoma drainage was designed, employing a microneedle and drainage layer structure, combined with graphene sensitive materials and a sensor detector, to achieve autonomous blood drainage and detection of multiple biomarkers.
It achieves painless, autonomous drainage and can detect blood bilirubin, blood glucose, blood C-reactive protein, and blood oxyhemoglobin, reducing neonatal pain and providing disease screening.
Smart Images
Figure CN121337349B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biosensor technology, and more specifically to an electronic patch for detecting hematoma drainage and its preparation method. Background Technology
[0002] During vaginal delivery, a newborn's head is easily compressed, which can cause subcutaneous blood vessels to rupture, resulting in a scalp hematoma. Mild scalp hematomas can be absorbed naturally, while moderate to severe hematomas require timely drainage. Otherwise, they can adversely affect the newborn's head development and, in severe cases, pose a life-threatening risk.
[0003] Surgical drainage is usually an effective treatment for neonatal scalp hematomas, but this carries certain risks and causes significant pain to the newborn. Using a specially designed negative pressure drainage device is an effective drainage method.
[0004] Current neonatal scalp hematoma drainage devices have the following limitations: 1. Draining subcutaneously with an injection needle can cause severe discomfort to newborns; 2. Direct extraction using a negative pressure device can also increase pain during the drainage process; 3. Newborns' blood contains physiological and pathological information, but the blood collected by scalp hematoma drainage devices cannot be fully utilized, and additional blood samples need to be collected for testing after birth. Summary of the Invention
[0005] This invention provides an electronic patch for hematoma drainage detection and its preparation method, with the aim of enabling autonomous drainage of hematoma and effective pathological detection of the drained blood.
[0006] The above objectives are achieved through the following technical solutions:
[0007] An electronic patch for detecting hematoma drainage includes a microneedle, a drainage layer fixed to the upper end face of the microneedle, a top cover fixed to the upper end of the microneedle, a temporary liquid collection chamber formed between the top cover and the microneedle, the drainage layer located in the liquid collection chamber, an integrated circuit fixed to the upper end of the top cover, a window provided in the center of the top cover, a sensor fixed to the lower end of the integrated circuit, and the sensor located in the liquid collection chamber through the window.
[0008] Microneedles are made of biocompatible metallic materials.
[0009] The metal material is stainless steel.
[0010] The flow-guiding layer includes PDMS foam, on which a hydrophilic hydrogel film is grown.
[0011] The sensor detector consists of four sets of electrodes and a gate located in the center of the four sets of electrodes, with each electrode modified with a sensitive material and a receptor.
[0012] The sensitive material is a graphene-sensitive material.
[0013] The receptors on the four electrodes are, respectively, antibilirubin antibody corresponding to blood bilirubin, boric acid corresponding to blood glucose, C-reactive protein nucleic acid aptamer corresponding to blood C-reactive protein, and anti-oxyhemoglobin antibody corresponding to oxyhemoglobin.
[0014] The wall formed by the microneedle and the top cover is provided with a pressure relief outlet. One end of the drainage tube is fixed to and connected to the wall, and the other end of the drainage tube is fixed to and connected to the collection bag.
[0015] A method for preparing an electronic patch for hematoma drainage detection includes the following steps:
[0016] Step 1: Use 3D printing technology to prepare microneedles and top caps, and prepare flow guide holes inside the microneedles;
[0017] Step 2: Using copper foam material as the base material, pour a mixture of PDMS prepolymer and curing agent into the copper foam. The mass ratio of PDMS prepolymer to cured material is 10:1. After curing, place it in a 10-15wt% ammonium persulfate solution until the copper is completely decomposed to obtain PDMS foam 21.
[0018] Spin-coat one side of the PDMS foam with an acetone solution containing 10-15 wt% benzoyl peroxide. After standing, rinse with ethanol and then immerse in an aqueous solution of 10-15 wt% acrylic acid and 1-2 wt% ammonium persulfate for UV curing to obtain a guide layer with a water contact angle that gradually decreases from bottom to top.
[0019] Step 3: Allow oxygen plasma to enter the liquid collection chamber through the window of the top cover. The contact rate in the central area is greater than that in the edge area, so that the inner wall of the lower part of the top cover, that is, the inner side of the upper end face of the temporary liquid collection chamber, has the characteristic that the water contact angle gradually decreases from the periphery to the center.
[0020] Step 4: Prepare four sets of electrodes and gates on a flexible PET film using electron beam evaporation or screen printing. Cut the graphene grown on copper foil into four 1×1mm pieces as the substrate. Electrolyze the copper foil at 2.3V as the cathodes to remove the copper foil and transfer it to the center of the four sets of electrodes. Immerse the electrodes in a 1-2mg / L concentration of graphene quantum dot aqueous solution. Drop 5-10μL of phosphate buffer solution containing 5-10μm receptors onto the surface of each of the four sets of graphene. After standing, the main body of the sensor detector is obtained.
[0021] Step 5: Secure the microneedles, the flow guide layer, and the top cover sequentially from bottom to top. The top cover has a window in the center. A sensor is fixed to the lower end of the integrated circuit, and the sensor passes through the window so that the electrodes, gate, and four types of receptors are located in the liquid collection chamber. The integrated circuit is fixed to the upper end of the top cover.
[0022] The four receptors are: anti-bilirubin antibody, pyrene-1-boronic acid, C-reactive protein aptamer, and anti-oxyhemoglobin antibody. The aptamer and antibody in the receptors are linked by a chemical reaction between the amino group (the amino group of the aptamer is added during synthesis, while the antibody generally has its own amino group) and the carboxyl group of the graphene quantum dots. The 1-pyrene-boronic acid corresponding to glucose is directly linked to the graphene through a benzene ring structure via π-π stacking. All four receptors are commercially available products.
[0023] The beneficial effects of the electronic patch for hematoma drainage detection and its preparation method of the present invention are as follows:
[0024] This invention uses graphene as the sensitive element for detection. Graphene quantum dots have the same hexagonal carbon structure as monolayer graphene and can be stacked with graphene sensitive materials. The carboxyl groups of graphene quantum dots can react with the amino groups of the receptor. The receptor can bind to the corresponding target biomarker in the blood, causing a change in the electrical properties of graphene. The higher the concentration of the biomarker, the greater the change. By applying a drain-source voltage and a changing gate voltage to graphene, the transfer characteristic curve of graphene can be obtained. By shifting the minimum value of the detection curve, the concentration of biomarkers in the blood can be detected.
[0025] Because the water contact angle of the guide layer in this invention gradually decreases from bottom to top, blood can be automatically transported from the scalp side to the liquid collection chamber without the need for traditional negative pressure devices, which can reduce the pain of newborns during the process of eliminating hematomas; the guide layer has a loose and porous foam-like structure, which can filter solid impurities such as blood cells in the blood, so as to facilitate subsequent testing.
[0026] This invention enables the detection of four or more biomarkers on the same flexible substrate using a common gate. By detecting blood bilirubin, blood glucose, blood C-reactive protein, and blood oxyhemoglobin concentration, it can effectively screen for common neonatal diseases such as jaundice, neonatal hypoglycemia, neonatal pneumonia, and neonatal respiratory distress syndrome. Attached Figure Description
[0027] Figure 1 This is a schematic diagram of the specific structure of an electronic patch for detecting scalp hematoma drainage in newborns, provided by the present invention.
[0028] Figure 2 This is a schematic diagram of the flow-through layer;
[0029] Figure 3 A schematic diagram of the wettability distribution in a temporary liquid collection chamber;
[0030] Figure 4 This is a schematic diagram of the electrode distribution;
[0031] Figure 5 This invention provides a flowchart of a method for preparing an electronic patch for detecting scalp hematoma drainage in newborns;
[0032] Figure 6 The graphene transfer characteristics of the blood bilirubin detection electrode prepared for the example to different concentrations of bilirubin are shown in the figure.
[0033] Figure 7 The graphene transfer characteristics of the blood glucose detection electrode prepared for the example to different concentrations of glucose are shown in the figure.
[0034] Figure 8 The graphene transfer characteristics of the blood C-reactive protein detection electrode prepared for this example for different concentrations of C-reactive protein are shown in the figure.
[0035] Figure 9 The graphene transfer characteristics of the oxygenated hemoglobin detection electrode prepared for this example for different concentrations of oxygenated hemoglobin are shown in the figure.
[0036] In the figure: 1. Microneedle; 2. Conduction layer; 21. PDMS foam; 22. Hydrogel film; 3. Top cover; 4. Liquid collection chamber; 5. Integrated circuit; 6. Drainage tube; 7. Electrode; 8. Gate. Detailed Implementation
[0037] An electronic patch for detecting hematoma drainage includes a microneedle 1. A groove is formed at the upper end of the microneedle 1. A drainage layer 2 is fixedly attached to the upper end face of the microneedle 1 within the groove. A drainage hole is built into the microneedle 1, allowing blood to be transported along the hole to the drainage layer 2. A top cover 3 is fixedly attached to the upper end of the microneedle 1, forming a temporary liquid collection chamber 4 between the top cover 3 and the microneedle 1. Therefore, the drainage layer 2 is located within the liquid collection chamber 4.
[0038] The microneedle 1 is made of a biocompatible metallic material. The flow-guiding layer 2 includes a PDMS foam 21 as the main component. The PDMS foam 21 has a loose and porous structure. A hydrophilic hydrogel film 22 is grown on the upper surface of the PDMS foam 21. Since the PDMS foam 21 itself is hydrophobic, blood can be spontaneously transported from the lower side to the upper side of the flow-guiding layer 2, and solid impurities in the blood can be blocked by the PDMS foam 21, which is more conducive to subsequent detection.
[0039] The top cover 3 is made of resin material used in 3D printing. The microneedles 1 and the top cover 3 can be separated and disassembled to allow for the insertion and replacement of the flow guide layer 2.
[0040] To further explain, the upper end of the cover 3 is fixedly connected to the integrated circuit 5, and a window is provided in the center of the cover 3. The lower end of the integrated circuit 5 is fixedly connected to the sensor 6, and the sensor 6 is located in the liquid collection chamber 4 through the window. The sensor 6 includes four sets of electrodes 7 and a central gate 8. The electrodes 7 are modified with a sensitive material and a receptor, and the sensitive material is graphene.
[0041] The inner wall structure of the upper cover 3 has a gradually decreasing water contact angle from the periphery to the center, which allows the blood in the liquid collection chamber 4 to spontaneously gather at the sensor detector 6. The electrode 7 is a planar flexible electrode; preferably, the material of the electrode 7 is metal, more preferably gold, and the gate 8 is silver / silver chloride.
[0042] The receptors mentioned correspond one-to-one with the target biological assays, preferably antibilirubin antibodies corresponding to blood bilirubin, boric acid corresponding to blood glucose, C-reactive protein nucleic acid aptamers corresponding to blood C-reactive protein, and anti-oxyhemoglobin antibodies corresponding to oxyhemoglobin.
[0043] To further explain, a pressure relief outlet 9 is provided on the wall formed by the microneedle 1 and the top cover 3. One end of the drainage tube 10 is fixed to and connected to the wall, and the other end of the drainage tube 10 is fixed to and connected to the collection bag 11.
[0044] The preparation method of the above-mentioned electronic patch for hematoma drainage detection includes the following steps:
[0045] Step 1: Microneedles 1 and top cover 3 are prepared using 3D printing technology. Microneedles 1 are preferably made of powdered 316L stainless steel material and are preferably processed using SLM laser full melting process. Top cover 3 is preferably made of photocurable resin material and preferably photocurable liquid epoxy resin material and is preferably processed using SLA stereolithography technology. Drainage holes are prepared inside microneedles 1 using ultraviolet lithography technology.
[0046] Step 2: Using copper foam as the substrate, a mixture of PDMS prepolymer and curing agent is poured into the interior of the copper foam. Typically, the PDMS prepolymer and curing agent are sold as a set; the matching PDMS curing agent can be directly sampled. The mass ratio of PDMS prepolymer to curing agent is 10:1. After curing at 80°C under vacuum for 3 hours, the foam is placed in a 10wt% ammonium persulfate solution until the copper is completely decomposed, yielding PDMS foam 21. This foam is then washed with deionized water and dried. A 10wt% benzoyl peroxide acetone solution is spin-coated onto one side of PDMS foam 21. After standing for 10 minutes, it is rinsed with ethanol, dried, and then immersed in a 10wt% acrylic acid and 1wt% ammonium persulfate aqueous solution for UV curing for 1 hour. The foam is then rinsed with deionized water and dried, yielding a guiding layer 2 with a water contact angle gradually decreasing from bottom to top.
[0047] Step 3: Place the upper surface of the cover 3 in an oxygen plasma cleaner for plasma treatment for 5 minutes and then remove it. This allows the oxygen plasma to enter the liquid collection chamber 4 through the window of the cover 3. The contact rate in the central area is greater than that in the edge area, so that the inner wall of the lower part of the cover 3, i.e. the inner side of the upper surface of the temporary liquid collection chamber, has the characteristic that the water contact angle gradually decreases from the periphery to the center.
[0048] Step 4: Prepare four sets of electrodes 7 and gate 8 on a flexible PET film using electron beam evaporation or screen printing. Cut the graphene grown on copper foil into four 1×1mm pieces as the substrate. Electrolyze the copper foil at 2.3V as the cathode and transfer it to the center of the four sets of electrodes 7. Wash with deionized water. Immerse the electrodes 7 in a 1mg / L graphene quantum dot aqueous solution for 3 hours. Wash with deionized water and dry. Add 5μL of phosphate buffer solution containing 10μm receptors to the surface of each of the four sets of graphene. The four receptors are: anti-bilirubin antibody, pyrene-1-boric acid, C-reactive protein aptamer, and anti-oxyhemoglobin antibody. After standing for 24 hours, wash with deionized water and dry to obtain the main body of the sensor detector 6.
[0049] Step 5: Secure the microneedle 1, the flow guide layer 2, and the top cover 3 from bottom to top. The top cover 3 has a window in the center. The sensor detector 6 is fixed to the lower end of the integrated circuit 5. The sensor detector 6 passes through the window, so that the electrode 7, the gate 8, and the four types of receptors are located in the liquid collection chamber 4. The integrated circuit 5 is fixed to the upper end of the top cover 3.
[0050] Test example:
[0051] 1. Using phosphate buffer (pH=7.4) as the solvent, prepare bilirubin solutions with concentrations of 0, 100 pm, 1 nm, 10 nm, 100 nm, 1 μm, and 10 μm. Add 40 μL of each solution to the surface of the blood bilirubin detection electrode. Apply a drain-source voltage of 0.006 V across the electrode, and a gate voltage of 0-0.5 V to the gate electrode. Record the relationship between the gate voltage and the drain-source current. The measurement results are as follows: Figure 6 As shown, the Dirac point (minimum) of the graphene transfer characteristic curve shifted by 0.72V, indicating that electrode 7 for detecting blood bilirubin has the ability to detect changes in bilirubin concentration.
[0052] 2. Using phosphate buffer (pH=7.4) as the solvent, prepare glucose solutions with concentrations of 0, 100 nm, 1 μm, 10 μm, 100 μm, 1 mm, and 10 mm. Add 40 μL of each solution to the surface of the bilirubin electrode 7. Apply a drain-source voltage of 0.006 V across the blood glucose measuring electrode 7. Apply a gate voltage of 0-0.5 V to the gate 8. Record the relationship between the gate voltage and the drain-source current. The measurement results are as follows: Figure 7 As shown, the Dirac point (minimum) of the graphene transfer characteristic curve shifted by 0.63V, indicating that the electrode 7 for detecting blood glucose has the ability to detect changes in glucose concentration.
[0053] 3. Using phosphate buffer (pH=7.4) as the solvent, prepare C-reactive protein solutions with concentrations of 0, 10 fm, 100 fm, 1 pm, 10 pm, 100 pm, and 1 nm. Add 40 μL of each solution to the surface of the blood C-reactive protein detection electrode. Apply a drain-source voltage of 0.006 V across the electrode, and a gate voltage of 0-0.5 V to the gate electrode. Record the relationship between the gate voltage and the drain-source current. The measurement results are shown below. Figure 8 As shown, the Dirac point (minimum) of the graphene transfer characteristic curve shifted by 0.69V, indicating that electrode 7 for detecting blood C-reactive protein has the ability to detect changes in C-reactive protein concentration.
[0054] 4. Using phosphate buffer (pH=7.4) as the solvent, prepare oxyhemoglobin solutions with concentrations of 0, 100 pm, 1 nm, 10 nm, 100 nm, 1 μm, and 10 μm. Add 40 μL of each solution to the surface of the oxyhemoglobin detection electrode. Apply a drain-source voltage of 0.006 V across the electrode, and a gate voltage of 0-0.5 V to the gate electrode. Record the relationship between the gate voltage and the drain-source current. The measurement results are shown below. Figure 9 As shown, the Dirac point (minimum) of the graphene transfer characteristic curve shifted by 0.65V, indicating that electrode 7 for detecting oxyhemoglobin has the ability to detect changes in oxyhemoglobin concentration.
[0055] Unless otherwise specified, all of the above-mentioned raw materials are commercially available products well known to those skilled in the art.
Claims
1. An electronic patch for detecting hematoma drainage, comprising a microneedle (1), a drainage layer (2) fixedly attached to the upper end face of the microneedle (1), a drainage hole built into the microneedle (1) to transport blood to the drainage layer (2) along the drainage hole, a top cover (3) fixedly attached to the upper end of the microneedle (1), a temporary liquid collection chamber (4) formed between the top cover (3) and the microneedle (1), the drainage layer (2) located in the liquid collection chamber (4), an integrated circuit (5) fixedly attached to the upper end of the top cover (3), a window provided in the center of the top cover (3), a sensor (6) fixedly attached to the lower end of the integrated circuit (5), and the sensor (6) located in the liquid collection chamber (4) through the window; The inner wall structure of the top cover (3) has the characteristic that the water contact angle gradually decreases from the periphery to the center, so that the blood in the liquid collection chamber (4) spontaneously gathers at the sensor detector (6). The sensing detector (6) comprises four sets of electrodes (7) and a gate (8) located in the center of the four sets of electrodes (7), each electrode (7) being modified with a sensitive material and a receptor.
2. In the electronic patch for hematoma drainage detection according to claim 1, the microneedle (1) is a biocompatible metal material.
3. The electronic patch for hematoma drainage detection according to claim 2, wherein the metal material is stainless steel.
4. The electronic patch for hematoma drainage detection according to claim 1, wherein the drainage layer (2) comprises PDMS foam (21), and a hydrophilic hydrogel film (22) is grown on the upper surface of the PDMS foam (21).
5. The electronic patch for detecting hematoma drainage according to claim 1, wherein the sensitive material is graphene.
6. The electronic patch for detecting hematoma drainage according to claim 5, wherein the receptors on the four electrodes (7) are respectively anti-bilirubin antibody corresponding to blood bilirubin, boric acid corresponding to blood glucose, C-reactive protein nucleic acid aptamer corresponding to blood C-reactive protein and anti-oxyhemoglobin antibody corresponding to oxyhemoglobin.
7. The electronic patch for hematoma drainage detection according to any one of claims 1 to 6, wherein a pressure relief outlet (9) is provided on the wall formed by the microneedle (1) and the top cover (3), one end of the drainage tube (10) is fixedly connected to and connected to the wall, and the other end of the drainage tube (10) is fixedly connected to and connected to the collection bag (11).
8. A method for preparing an electronic patch for detecting hematoma drainage, comprising the following steps: Step 1: Use 3D printing technology to prepare microneedles (1) and top cover (3), and prepare flow guide holes inside microneedles (1); Step 2: Using copper foam material as the base material, pour a mixture of PDMS prepolymer and curing agent into the copper foam. The mass ratio of PDMS prepolymer to cured material is 10:
1. After curing, place it in a 10-15wt% ammonium persulfate solution until the copper is completely decomposed to obtain PDMS foam 21. Spin-coat one side of PDMS foam (21) with 10-15wt% benzoyl peroxide in acetone solution, let stand, rinse with ethanol, and then immerse in an aqueous solution of 10-15wt% acrylic acid and 1-2wt% ammonium persulfate for UV curing to obtain a guide layer (2) with a water contact angle that gradually decreases from bottom to top. Step 3: Allow oxygen plasma to enter the liquid collection chamber (4) through the window of the upper cover (3). The contact rate in the central area is greater than that in the edge area, so that the inner wall of the lower part of the upper cover (3), that is, the inner side of the upper surface of the temporary liquid collection chamber, has the characteristic that the water contact angle gradually decreases from the periphery to the center. Step 4: Prepare four sets of electrodes (7) and gate (8) on a flexible PET film using electron beam evaporation or screen printing. Cut the graphene grown on copper foil into four pieces of 1×1mm size as the substrate. Electrolyze the copper foil at 2.3V to remove it as the cathode and transfer it to the center of the four sets of electrodes (7). Immerse the electrodes (7) in a 1-2mg / L concentration of graphene quantum dot aqueous solution. Add 5-10μL of 5-10μm phosphate buffer solution of the receptor to the surface of the four sets of graphene. After standing, obtain the main body of the sensor detector (6). Step 5: Secure the microneedle (1), the flow guide layer (2) and the top cover (3) from bottom to top. The top cover (3) has a window in the center. The sensor detector (6) is fixed at the lower end of the integrated circuit (5). The sensor detector (6) passes through the window, so that the electrode (7), the gate (8) and the four types of receptors are located in the liquid collection chamber (4). The integrated circuit (5) is fixed at the upper end of the top cover (3).
9. The method for preparing an electronic patch for hematoma drainage detection according to claim 8, wherein the four receptors are: anti-bilirubin antibody, pyrene-1-boronic acid, C-reactive protein aptamer and anti-oxyhemoglobin antibody.