WO2023060669A1 - 基于碳管/mxenes的标志物检测装置及其制备方法 - Google Patents

基于碳管/mxenes的标志物检测装置及其制备方法 Download PDF

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WO2023060669A1
WO2023060669A1 PCT/CN2021/128363 CN2021128363W WO2023060669A1 WO 2023060669 A1 WO2023060669 A1 WO 2023060669A1 CN 2021128363 W CN2021128363 W CN 2021128363W WO 2023060669 A1 WO2023060669 A1 WO 2023060669A1
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probe
probes
detection device
hollow
catheter
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PCT/CN2021/128363
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English (en)
French (fr)
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谢曦
黄爽
陈惠琄
杭天
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中山大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14503—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6848—Needles
    • A61B5/6849—Needles in combination with a needle set
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6852—Catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6852—Catheters
    • A61B5/6859—Catheters with multiple distal splines
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to the field of biological detection, in particular to a carbon tube/Mxenes-based marker detection device and a preparation method thereof.
  • Minimally invasive surgery is used in the diagnosis and treatment of health conditions, cancer, cardiovascular disease and urological diseases as advanced diagnostic and therapeutic methods continue to increase.
  • One of the most convincing representatives is the laparoscopic catheter, which can record basic biological information during surgery.
  • the items that can be detected in the endoscope are very limited at present, and the limited detection types need to insert multiple catheters with different detection object lenses; some important biomarkers must be detected by biopsy, which cannot meet the requirements of real-time and in situ detection.
  • Conventional enzyme electron mediators are mostly based on small molecular substances such as Prussian blue. Such small molecular mediators have certain biological safety hazards and are not suitable for use in vivo.
  • the purpose of the embodiments of the present invention is to provide a marker detection device based on carbon tubes/Mxenes and its preparation method, which can realize minimally invasive, rapid, in situ and multifunctional marker detection.
  • MXene materials are a class of metal carbides and metal nitrides with a two-dimensional layered structure.
  • an embodiment of the present invention provides a marker detection device based on carbon tubes/Mxenes, including a catheter, a wire disposed in the catheter, a probe substrate sealed and bonded to one end of the catheter, The probe array arranged on the first end surface of the probe substrate, the wires are used to connect the probe array and external equipment, and the probe array is decorated with detection sensitive substances containing carbon tubes/Mxenes composite material .
  • the detection device further includes an elastic unit, the first end surface of the elastic unit is fixedly connected to the second end surface of the probe substrate, and the second end surface of the elastic unit is fixedly connected to the pushing module.
  • the detection device further includes a drug release unit disposed in the conduit, the drug release unit includes a hollow probe and a microfluidic conduit, and the hollow probe is disposed on the first probe substrate. One end face, one end of the microfluidic conduit is fixedly connected with the hollow probe.
  • the detection device further includes an electrical stimulation electrode disposed in the catheter, the electrical stimulation electrode includes an electrode and a wire, and one end of the wire is fixedly connected to the electrode.
  • the type of the probe array includes one or more of solid probes, hollow probes, coated probes or soluble probes.
  • an embodiment of the present invention provides a method for preparing a marker detection device based on carbon tubes/Mxenes, including:
  • the probe substrate is hermetically attached to the nozzle at one end of the conduit.
  • the preparation method of the carbon tube/Mxenes composite material is as follows:
  • the solid probes and hollow probes of the probe array when the probe array is a hollow probe, the preparation method of the hollow probe is as follows:
  • Hollow probes are obtained by 3D printing polymer materials.
  • the solid probes and hollow probes of the probe array when the probe array is a solid probe, the preparation method of the solid probe is as follows:
  • Solid probes are obtained by laser cutting metallic material.
  • the carbon tube/Mxenes composite material in the embodiment of the present invention has good biocompatibility, good electrical conductivity, high specific surface area and has the function of an electron mediator.
  • the needle array is modified with detection sensitive substances containing carbon tubes/Mxenes composite materials; the catheter is used as a carrier to send the probe array to the site to be detected without damaging the body, and the probe array enters the mucosa by virtue of the penetrability of the probe Tissue detection markers; thus realizing minimally invasive, rapid and versatile marker detection.
  • Fig. 1 is a schematic structural diagram of a marker detection device based on carbon tubes/Mxenes provided by an embodiment of the present invention
  • Fig. 2 is a display diagram showing the results of detecting glucose with different materials modified by a probe provided in an embodiment of the present invention
  • Fig. 3 is a schematic structural view of several different modified materials and different sensor devices provided by the embodiment of the present invention.
  • Fig. 4 is a schematic flow chart of the steps of a preparation method of a marker detection device based on carbon tubes/Mxenes provided by an embodiment of the present invention
  • FIG. 5 is a schematic structural view of a probe modified with a carbon tube/Mxene composite material provided by an embodiment of the present invention
  • Fig. 6 is a schematic structural diagram of a marker detection device based on carbon tubes/Mxenes provided by an embodiment of the present invention for detecting markers in organs.
  • An embodiment of the present invention provides a marker detection device based on carbon tubes/Mxenes, which includes a catheter, a wire disposed in the catheter, a probe substrate that is sealed and bonded to one end of the catheter, and a probe substrate disposed in the catheter.
  • the probe array on the first end surface of the probe substrate, the wires are used to connect the probe array and external equipment, and the probe array is decorated with detection sensitive objects of carbon tube/Mxenes composite material.
  • the working principle of the detection device is as follows: After the probe array modified with the detection sensitive substance containing carbon tubes/Mxenes composite material penetrates the skin or mucous membrane, after the detection sensitive substance is in full contact with the analyte, the electrical signal detected by the probe array It is transmitted to external devices for processing or display through wires.
  • the detection device further includes an elastic unit, the first end surface of the elastic unit is fixedly connected to the second end surface of the probe substrate, and the second end surface of the elastic unit is fixedly connected to the pushing module.
  • the probe needs a power to enter the mucosa, and the power can be obtained from manual push, but it is difficult to achieve manual push in the hose or deep in the body, and the realization depends entirely on manual force. Operability is not strong.
  • the elastic unit can achieve precise application of force to penetrate the mucous membrane or skin, and the elastic unit can be a self-made spring unit, a purely mechanical unit or a gas push unit.
  • connection between the elastic unit and the probe substrate mainly depends on glue bonding.
  • the mechanical properties of the glue are not stable enough, and it is easy to fall off after multiple application of force; therefore, the elastic unit and the probe substrate can adopt a more stable mechanical combination method. Improve system stability.
  • the detection device further includes a drug release unit disposed in the conduit, the drug release unit includes a hollow probe and a microfluidic conduit, and the hollow probe is disposed on the first probe substrate. One end face, one end of the microfluidic conduit is fixedly connected with the hollow probe.
  • the detection device detects a certain signal, it may be necessary to administer medication, and the medication can be administered through the drug release unit, which is convenient, fast and time-sensitive.
  • the detection device further includes an electrical stimulation electrode disposed in the catheter, the electrical stimulation electrode includes an electrode and a wire, and one end of the wire is fixedly connected to the electrode.
  • electrotherapy when the detection device detects a certain signal, electrotherapy may be required, and if tumor-like substances are detected, electrotherapy can be performed through the electrical stimulation electrodes.
  • wires can be welded and integrated or bundled to pass through the conduit, and the microfluidic pipeline can be bundled to pass through the conduit.
  • the type of the probe array includes one or more of solid probes, hollow probes, coated probes or soluble probes.
  • the minimally invasive surgical catheter 1-1 contains a guide wire or a microfluidic pipeline 1-2, and one end of the minimally invasive surgical catheter 1-1 is provided with a microneedle array 1-3 with different functions.
  • the partial enlarged view of the microneedle array 1-3 of different functions includes probe array 1-4, probe substrate 1-5 and elastic unit 1-6;
  • probe arrays 1-4 include probes 1-7, hollow probes 1-8, coated probes 1-9 and soluble probes 1 modified with detection sensitive substances containing carbon tubes/Mxenes composites -10.
  • Figure 2(a) shows the results of modifying the stainless steel probe with different materials, then modifying glucose oxidase and detecting glucose. From the inspection results in Figure 2(a), it can be seen that compared with the probes without modification or with carbon tubes, The detection performance of the probe modified with CNT/Mxene has been significantly improved.
  • Figure 2(b) shows the results of measuring glucose with gold probes modified with Prussian blue/glucose oxidase
  • Figure 2(c) shows the results of measuring glucose with gold probes modified with carbon tubes/Mxene/glucose oxidase It shows that according to the measurement results in Figure 2(b) and Figure 2(c), the performance of the same probe modified by the carbon tube/MXene material is better than that of the commonly used Prussian blue small molecule, which also shows that the carbon tube /MXene materials can replace Prussian blue electron mediator materials with poorer biocompatibility in terms of sensing performance.
  • the carbon tube/Mxenes composite material in the embodiment of the present invention has good biocompatibility, good electrical conductivity, high specific surface area and has the function of an electron mediator.
  • the needle array is modified with detection sensitive substances containing carbon tubes/Mxenes composite materials; the catheter is used as a carrier to send the probe array to the site to be detected without damaging the body, and the probe array enters the mucosa by virtue of the penetrability of the probe Tissue detection markers; thus realizing minimally invasive, rapid and versatile marker detection.
  • 2-1 represents the catheter for minimally invasive surgery
  • 2-2 represents the elastic unit
  • 2-3 represents the wire or microfluidic channel
  • 2-4 represents the planar biochemical sensor at the top of the catheter
  • 2-6 represents the Skin or mucous membrane containing a variety of biochemical index substances
  • the elastic unit 2-2 and the wire or microfluidic conduit 2-3 are set in the catheter 2-1 for minimally invasive surgery, and the wire or microfluidic conduit 2-3 passes through the elastic unit 2-2 Connect with planar biochemical sensors 2-4.
  • the sensor device into the organ to be tested (such as the bladder), and contact the planar biochemical sensor 2-4 with the surface of the skin or mucous membrane 2-6, because the planar biochemical sensor 2-4 is difficult to penetrate the skin or mucous membrane 2-6 , the sensing sensitive material on the planar biochemical sensor 2-4 is not in sufficient contact with the test object under the skin or mucous membrane 2-6, so the biochemical indicators under the skin or mucous membrane 2-6 to be tested cannot be accurately obtained, let alone simultaneously detected A variety of biochemical indicators.
  • 3-1 represents the catheter for minimally invasive surgery
  • 3-2 represents the elastic unit
  • 3-3 represents the wire or microfluidic channel
  • 3-5 represents the sensor array at the top of the catheter
  • 3-6 represents the sensor array containing
  • 3-7 represents the sensing material layer of Prussian blue or other traditional materials
  • the elastic unit 3-2 and the wire or microfluidic pipeline 3-3 are arranged in the catheter 3-1 for minimally invasive surgery
  • the wire or the microfluidic channel 3-3 is connected to the sensor array 3-5 through the elastic unit 3-2.
  • the sensing device is inserted into the organ to be measured (such as the bladder), and the sensor array 3-5 is inserted into the skin or mucous membrane 3-6.
  • the sensing material layer 3-7 Since the sensing material layer 3-7 is fully in contact with the object to be measured, it can be more accurate. Obtain the biochemical index under the skin or mucous membrane 3-6 to be tested, but cannot detect multiple biochemical indexes at the same time. In addition, due to the poor biocompatibility of small molecules such as Prussian blue, certain side effects will occur in the damaged part of the body.
  • 4-1 represents the catheter for minimally invasive surgery
  • 4-2 represents the elastic unit
  • 4-3 represents the wire or microfluidic channel
  • 4-5 represents the sensor array at the top of the catheter
  • 4-6 represents the sensor array containing The skin or mucous membrane of various biochemical indicator substances
  • 4-8 means the ionic sensing material layer based on carbon tube/Mxenes composite material
  • 4-9 means the catalyst type sensing material layer based on carbon tube/Mxenes composite material
  • 4-10 means Based on the carbon tube/Mxenes composite biological enzyme type sensing material layer
  • 4-11 represents the sensing material layer based on other mechanisms of the carbon tube/Mxenes composite material
  • the elastic unit 4-2 and the wire or microfluidic pipeline 4-3 are arranged on In the catheter 4-1 for minimally invasive surgery, the wire or microfluidic channel 4-3 is connected to the sensor array 4-5 through the elastic unit 4-2.
  • the sensing device is inserted into the organ to be measured (such as the bladder), and the sensor array 4-5 is inserted into the skin or mucous membrane 4-6, since the sensing material layer (4-8, 4-9, 4-10 or 4 -11) It is in sufficient contact with the test object, so it can accurately obtain multiple biochemical indicators under the skin or mucous membrane 4-6 to be tested, and the device can detect multiple biochemical indicators at the same time. In addition, due to the good biocompatibility of carbon materials and the small damage area, the side effects on the human body are negligible.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, Then Pt-glucose is modified to detect glucose.
  • Glucose is located inside the hollow probe, which penetrates the mucosa through the hollow probe and contacts with the interstitial fluid. The rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, The Pt-uricase is then modified to detect uric acid.
  • the uricase is located inside the hollow probe, which penetrates the mucous membrane through the hollow probe and contacts the interstitial fluid. The rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, The Ca ion membrane is then modified to detect Ca ions.
  • the Ca ion membrane is located inside the hollow probe, which penetrates the mucosa through the hollow probe and contacts the interstitial fluid. The rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, The K ion membrane is then modified to detect K ions.
  • the K ion membrane is located inside the hollow probe, which penetrates the mucous membrane through the hollow probe and contacts the interstitial fluid.
  • the rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, The Na ion membrane is then modified to detect Na ions.
  • the Na ion membrane is located inside the hollow probe, which penetrates the mucous membrane through the hollow probe and contacts the interstitial fluid.
  • the rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • the probe arrays are obtained by printing red wax materials with 3D printing technology, all probes are hollow probes, and the wires of the sensing part are made of gold wires; carbon tubes/MXene are modified on the 800um part of the probes, The pH ion membrane is then modified to detect pH ions.
  • the pH ion membrane is located inside the hollow probe, which penetrates the mucous membrane through the hollow probe and contacts the interstitial fluid.
  • the rest of the gold wire is insulated and connected to the outside.
  • the hollow probe can be used for test sensing directly through the lead, or for drug delivery through the catheter.
  • an embodiment of the present invention provides a method for preparing a marker detection device based on carbon tubes/Mxenes, including:
  • the probe array can be prepared by microfabrication of metal probes or polymer probe arrays, or by 3D printing polymer insulating probes in various forms such as resin or red wax.
  • a multifunctional sensing array is constructed.
  • the probe arrays are all 3D printed, all probes are made of red wax material in the form of hollow probes, the conductive wires of the sensing part are made of gold wires, and the 800um tip part is first decorated with a layer of carbon tubes/Mxenes
  • the composite material as shown in Figure 5, is modified on the composite material with detection substances such as glucose enzyme, uricase, calcium ion membrane, and lactase.
  • the detection substance is located inside the hollow probe, and after penetrating the mucosa through the hollow probe, it is mixed with the interstitial fluid. contact, and the rest of the gold wire is insulated and connected externally.
  • detection substances such as glucose enzyme, uricase, calcium ion membrane, and lactase.
  • the length of the sensing probe part is generally controlled at 300-1000um according to the thickness of the cortex at the measurement location.
  • the probe substrate is a PI (Polyimide, polyimide) substrate or other polymer insulating substrates.
  • each probe has an independent sensing function, so the conductive functional part of each individual functional probe is connected to it by a wire, and the wire and the probe are connected by welding or silver paste connection.
  • the dots are packaged and fixed with parylene or superglue.
  • an elastic unit such as an air balloon or a spring
  • an elastic unit such as an air balloon or a spring
  • the drug release unit adopts a hollow probe, and each hollow drug delivery probe is fixed with a microfluidic channel inside, and the microfluidic channel and the hollow probe are directly packaged and fixed with superglue Just expose the microfluidic nozzle.
  • the detection device also includes electrical stimulation electrodes
  • the conductive functional parts of each individual electrical stimulation electrode are connected with wires, and the wires and electrical stimulation electrodes are connected by welding or silver paste, and the connection points are made of parylene or Super glue package fixed.
  • the integrated probe array lining is attached to the surgical catheter: firstly, the wire and the microfluidic pipeline are placed inside the surgical catheter, and the wires are extended from the channel reserved by the elastic unit and fixed, and the probe array substrate and the elastic The unit is bonded and fixed with super glue, and then packaged and bonded with the wall of the surgical pipeline (PDMS and other materials with good biocompatibility and good toughness can be used for packaging), ensuring good adhesion and air tightness between the pipeline and the probe substrate. Tightness. Finally, connect the wires and microfluidic channels protruding from the outside of the surgical catheter to external commercial instruments, and use it with a laparoscope, and use the laparoscope to send the device to the site to be tested.
  • PDMS and other materials with good biocompatibility and good toughness can be used for packaging
  • 6-1 represents a speculum
  • 6-2 represents a micro-interventional catheter with a multi-parameter probe
  • 6-3 represents a detection device used in conjunction with the speculum
  • 6-4 represents a human organ, such as Bladder, through the speculum 6-1, the micro-intervention catheter 6-2 containing the multi-parameter probe of the detection device 6-3 is sent to the bladder 6-4 to detect uric acid.
  • the preparation method of the carbon tube/Mxenes composite material is as follows:
  • the solvent of the carbon tube/MXene mixture can be water or an organic solvent such as IPA (isopropanol), and a certain amount of carbon tube solution and MXene solution are drawn with a pipette gun The mixture is placed in a container and fully mixed.
  • the content of carbon tubes in the prepared mixed solution is 1%-5%, and the content of MXene is 0.5%-4%.
  • the solid probes and hollow probes of the probe array when the probe array is a hollow probe, the preparation method of the hollow probe is as follows:
  • Hollow probes are obtained by 3D printing polymer materials.
  • the polymer material includes materials such as resin or red wax.
  • the solid probes and hollow probes of the probe array when the probe array is a solid probe, the preparation method of the solid probe is as follows:
  • Solid probes are obtained by laser cutting metallic material.
  • the probe array is a solid probe, such as a metal probe prepared by laser cutting
  • the metal probe is directly welded on the PI substrate or other polymer insulating substrates, because the PI substrate can be directly formed by micro Multiple independent traces are processed and flexible so that each solid metal probe can be directly connected to the external circuit separately.
  • a multifunctional sensing array is constructed by modifying various detection sensitivities of the carbon tube/Mxenes composite material on the surface of the probe respectively.
  • the drug delivery unit can be welded to the drug delivery hole of the PI substrate by using a metal hollow needle alone, and the drug is connected to the PI drug delivery hole through an externally introduced microtube.
  • the carbon tube/Mxenes composite material in the embodiment of the present invention has good biocompatibility, good electrical conductivity, high specific surface area and has the function of an electron mediator.
  • the needle array is modified with detection sensitive substances containing carbon tubes/Mxenes composite materials; the catheter is used as a carrier to send the probe array to the site to be detected without damaging the body, and the probe array enters the mucosa by virtue of the penetrability of the probe Tissue detection markers; thus realizing minimally invasive, rapid and versatile marker detection.

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Abstract

本发明公开了一种基于碳管/MXenes的标志物检测装置及其制备方法，检测装置包括导管、设置于导管内的导线、与所述导管的一端管口密封贴合的探针衬底、设置于所述探针衬底的第一端面的探针阵列，所述导线用于连接所述探针阵列及外部设备，所述探针阵列修饰有含碳管/MXenes复合材料的检测敏感物。本发明实施例可实现微创、快速、原位及多功能的标志物检测，可广泛应用于生物检测领域。

Description

基于碳管/Mxenes的标志物检测装置及其制备方法
本公开基于申请号为202111186869.6，申请日为2021年10月12日的中国专利申请提出，并要求该篇中国专利申请的优先权，该篇中国专利申请的全部内容在此引入本申请作为参考。
技术领域
本发明涉及生物检测领域，尤其涉及一种基于碳管/Mxenes的标志物检测装置及其制备方法。
背景技术
随着先进诊断和治疗手段的不断增多，微创手术被应用于健康状况、癌症、心血管疾病和泌尿系统疾病的诊断和治疗中。腔镜导管是最有说服力的代表之一，它可以记录手术过程中的基本生物信息。然而，目前腔镜内能检测的项目是非常有限，并且有限的检测类型需要插入多个带不同检测物镜头的导管；一些重要生物标志物必须通过活检进行检测，不能满足实时、原位检测的要求；常规的酶电子介体多基于普鲁士蓝等小分子物质，这类小分子介体具有一定的生物安全隐患而不适合应用于体内。
发明内容
有鉴于此，本发明实施例的目的是提供一种基于碳管/Mxenes的标志物检测装置及其制备方法，能够实现微创、快速、原位及多功能的标志物检测。
MXene材料是一类具有二维层状结构的金属碳化物和金属氮化物材。
第一方面，本发明实施例提供了一种基于碳管/Mxenes的标志物检测装置，包括导管、设置于导管内的导线、与所述导管的一端管口密封贴合的探针衬底、设置于所述探针衬底的第一端面的探针阵列，所述导线用于连接所述探针阵列及外部设备，所述探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物。
可选地，所述检测装置还包括弹性单元，所述弹性单元的第一端面固定连接所述探针衬底的第二端面，所述弹性单元的第二端面固定连接推送模块。
可选地，所述检测装置还包括设置于所述导管内的药物释放单元，所述药物释放单元包括空心探针和微流导管，所述空心探针设置于所述探针衬底的第一端面，所述微流导管的一端固定连接所述空心探针。
可选地，所述检测装置还包括设置于所述导管内的电刺激电极，所述电刺激电极包括电极和导线，所述导线的一端固定连接所述电极。
可选地，所述探针阵列的类型包括实心探针、空心探针、包衣探针或可溶性探针中的一 种或多种。
第二方面，本发明实施例提供了一种基于碳管/Mxenes的标志物检测装置的制备方法，包括：
制备探针阵列，并在所述探针阵列的表面或内部修饰含碳管/Mxenes复合材料的检测敏感物；
将所述探针阵列设置于探针衬底的第一端面；
将导线通过导管内部后与所述探针阵列连接；
将所述探针衬底密封贴合在所述导管的一端管口。
可选地，所述碳管/Mxenes复合材料的制备方法如下：
将碳管和Mxenes按照预设含量溶于水或有机溶液中，并充分混合。
可选地，所述探针阵列的实心探针和空心探针，当所述探针阵列为空心探针，所述空心探针的制备方法如下：
通过3D打印高分子材料获得空心探针。
可选地，所述探针阵列的实心探针和空心探针，当所述探针阵列为实心探针，所述实心探针的制备方法如下：
通过激光切割金属材料获得实心探针。
实施本发明实施例包括以下有益效果：本发明实施例中的碳管/Mxenes复合材料具有良好的生物相容性、较好的导电性、较高的比表面积且具有电子介体的功能，探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物；通过导管作为载体，在不损伤机体的前提下将探针阵列送到待检测部位，探针阵列借助探针的穿透性进入黏膜组织检测标志物；从而实现微创、快速及多功能的标志物检测。
附图说明
图1是本发明实施例提供的一种基于碳管/Mxenes的标志物检测装置的结构示意图；
图2是本发明实施例提供的一种探针修饰不同材料检测葡萄糖的结果显示图；
图3是本发明实施例提供的几种不同修饰材料和不同传感器件的结构示意图；
图4是本发明实施例提供的一种基于碳管/Mxenes的标志物检测装置的制备方法的步骤流程示意图；
图5是本发明实施例提供的一种修饰有碳管/Mxene复合材料的探针的结构示意图；
图6是本发明实施例提供的一种基于碳管/Mxenes的标志物检测装置用于检测器官内标志物的结构示意图。
具体实施方式
下面结合附图和具体实施例对本发明做进一步的详细说明。对于以下实施例中的步骤编号，其仅为了便于阐述说明而设置，对步骤之间的顺序不做任何限定，实施例中的各步骤的执行顺序均可根据本领域技术人员的理解来进行适应性调整。
本发明实施例提供了一种基于碳管/Mxenes的标志物检测装置，包括导管、设置于导管内的导线、与所述导管的一端管口密封贴合的探针衬底、设置于所述探针衬底的第一端面的探针阵列，所述导线用于连接所述探针阵列及外部设备，所述探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物。
检测装置的工作原理如下：将修饰有含碳管/Mxenes复合材料的检测敏感物的探针阵列穿透皮肤或粘膜后，检测敏感物与待测物充分接触后，探针阵列检测的电信号通过导线传输给外部设备进行处理或显示等。
可选地，所述检测装置还包括弹性单元，所述弹性单元的第一端面固定连接所述探针衬底的第二端面，所述弹性单元的第二端面固定连接推送模块。
本领域技术人员可以理解的是，探针进入黏膜需要一个动力，动力可以从手动推入获取，但手动推入在软管内或身体深处则难以实现，且实现完全靠人为手动给力，可操作性不强。弹性单元可以实现精准施力插破黏膜或皮肤，弹性单元可以是自制弹簧单元、纯机械单元或气体推动单元。
弹性单元与探针衬底的连接主要依靠胶水粘黏贴合，胶水的力学性能不够稳定，容易在多次施力后脱落；因此，弹力单元与探针衬底可采用更加稳定的机械结合方式提高系统的稳定性。
可选地，所述检测装置还包括设置于所述导管内的药物释放单元，所述药物释放单元包括空心探针和微流导管，所述空心探针设置于所述探针衬底的第一端面，所述微流导管的一端固定连接所述空心探针。
需要说明的是，当检测装置到某种信号后，可能需要进行给药治疗，则可以通过药物释放单元进行给药，方便、快捷且时效性好。
可选地，所述检测装置还包括设置于所述导管内的电刺激电极，所述电刺激电极包括电极和导线，所述导线的一端固定连接所述电极。
需要说明的是，当检测装置到某种信号后，可能需要进行电疗，若检测到肿瘤类物质，可以通过电刺激电极进行电疗。
需要说明的是，导线可以采用焊接集成或捆绑整束通过导管，微流管道以采用捆绑整束通过导管。
可选地，所述探针阵列的类型包括实心探针、空心探针、包衣探针或可溶性探针中的一 种或多种。
具体地，如图1(a)所示，微创手术导管1-1内部包含导线或微流管道1-2，微创手术导管1-1的一端设有不同功能的微针阵列1-3；如图1(b)所示，不同功能的微针阵列1-3的局部放大图包括探针阵列1-4、探针衬底1-5及弹性单元1-6；如图1(c)所示，探针阵列1-4包括修饰有含碳管/Mxenes复合材料的检测敏感物的探针1-7、空心探针1-8、包衣探针1-9及可溶性探针1-10。
在进行生理指标检测时，需要检测的物质准确度较高，准确度为X±10％。图2(a)为不锈钢探针修饰不同材料后，再修饰葡萄糖氧化酶并检测葡萄糖的结果，从图2(a)的检查结果可知，相比于无修饰或修饰有碳管的探针，修饰有碳管/Mxene的探针的检测性能具有显著提升。图2(b)为修饰有普鲁士蓝/葡萄糖氧化酶修饰的金探针测量葡萄糖的结果显示，图2(c)为修饰有碳管/Mxene/葡萄糖氧化酶修饰的金探针测量葡萄糖的结果显示，根据图2(b)及图2(c)的测量结果可知，经碳管/MXene材料修饰过的同种探针，性能比现在常用的普鲁士蓝小分子更好，也说明了碳管/MXene材料可以在传感性能方面代替生物相容性更差的普鲁士蓝电子介体材料。
实施本发明实施例包括以下有益效果：本发明实施例中的碳管/Mxenes复合材料具有良好的生物相容性、较好的导电性、较高的比表面积且具有电子介体的功能，探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物；通过导管作为载体，在不损伤机体的前提下将探针阵列送到待检测部位，探针阵列借助探针的穿透性进入黏膜组织检测标志物；从而实现微创、快速及多功能的标志物检测。
下面以几个具体实施例进行说明。
实施例一
如图3(a)所示，2-1表示微创手术导管，2-2表示弹性单元，2-3表示导线或微流管道，2-4表示导管顶端的平面生化传感器，2-6表示含多种生化指标物质的皮肤或粘膜；弹性单元2-2和导线或微流管道2-3设置于微创手术导管2-1中，导线或微流管道2-3通过弹性单元2-2与平面生化传感器2-4连接。将该传感器件伸入待测器官(如膀胱)部位，并将平面生化传感器2-4与皮肤或粘膜2-6表面接触，由于平面生化传感器2-4很难插破皮肤或粘膜2-6，平面生化传感器2-4上的传感敏感材料与皮肤或粘膜2-6下的待测物未充分接触，因此不能准确获得待测皮肤或粘膜2-6下的生化指标，更不能同时检测多种生化指标。
实施例二
如图3(b)所示，3-1表示微创手术导管，3-2表示弹性单元，3-3表示导线或微流管道，3-5表示导管顶端的传感器阵列，3-6表示含多种生化指标物质的皮肤或粘膜，3-7表示普鲁 士蓝或其它传统材料的传感材料层；弹性单元3-2和导线或微流管道3-3设置于微创手术导管3-1中，导线或微流管道3-3通过弹性单元3-2与传感器阵列3-5连接。将该传感器件伸入待测器官(如膀胱)部位，并将传感器阵列3-5插入皮肤或粘膜3-6中，由于传感材料层3-7与待测物接触充分，因此能较准确获得待测皮肤或粘膜3-6下的该生化指标，但不能同时检测多种生化指标。另外，由于普鲁士蓝等小分子的生物相容性差，因此该肌体破损处会产生一定副作用。
实施例三
如图3(c)所示，4-1表示微创手术导管，4-2表示弹性单元，4-3表示导线或微流管道，4-5表示导管顶端的传感器阵列，4-6表示含多种生化指标物质的皮肤或粘膜，4-8表示基于碳管/Mxenes复合材料离子型传感材料层，4-9表示基于碳管/Mxenes复合材料催化剂型传感材料层，4-10表示基于碳管/Mxenes复合材料生物酶型传感材料层，4-11表示基于碳管/Mxenes复合材料其它机制的传感材料层；弹性单元4-2和导线或微流管道4-3设置于微创手术导管4-1中，导线或微流管道4-3通过弹性单元4-2与传感器阵列4-5连接。将该传感器件伸入待测器官(如膀胱)部位，并将传感器阵列4-5插入皮肤或粘膜4-6中，由于传感材料层(4-8、4-9、4-10或4-11)与待测物接触充分，因此能较准确获得待测皮肤或粘膜4-6下的多种生化指标，且该器件能同时检测多种生化指标。另外，由于碳类材料的生物相容性良好，且该破损处面积较小，因此对肌体产生的副作用可忽略不计。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰Pt-葡萄糖酶以检测葡萄糖，葡萄糖酶位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰Pt-尿酸酶以检测尿酸，尿酸酶位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰Ca离子膜以检测Ca离子，Ca离子膜位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰K离子膜以检测K 离子，K离子膜位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰Na离子膜以检测Na离子，Na离子膜位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
可选地，探针阵列均采取3D打印技术打印红蜡材料获得，所有探针均为空心探针，传感部分的导线由金线制成；在探针的800um部分修饰碳管/MXene，再修饰pH离子膜以检测pH离子，pH离子膜位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。空心探针可直接通过导线进行测试传感，或通过导管进行给药。
如图4所示，本发明实施例提供了一种基于碳管/Mxenes的标志物检测装置的制备方法，包括：
S100、制备探针阵列，并在所述探针阵列的表面或内部修饰含碳管/Mxenes复合材料的检测敏感物。
具体地，探针阵列可通过微加工的方法制备金属探针或者高分子探针阵列，也可以通过3D打印树脂或红蜡等多种形态的高分子绝缘探针。通过在探针表面或者空心探针内部修饰含碳管/Mxenes复合材料的多种检测敏感物，构建具有多功能的传感阵列。
例如：探针阵列均由3D打印得来，所有探针均采用空心探针的形式由红蜡材料构成，传感部分导电线为金线制成，尖端800um部分先修饰一层碳管/Mxenes复合材料，如图5所示，再在该复合材料上修饰葡萄糖酶、尿酸酶、钙离子膜、乳糖酶等检测物质，检测物质位于空心探针内部，通过空心探针穿透黏膜后与组织液接触，金线其余部分进行绝缘与外部连接。图5中，1表示探针，2表示修饰在探针表面的碳管/Mxene复合材料，3表示块状的Mxene材料，4表示线状的碳管材料。在尖端800um部分先修饰一层碳管/Mxene复合材料的原因在于：人体皮肤厚度一般为500um-4000um之间，皮肤分表皮和真皮两层，表皮层没有神经和血管，厚度为70um-1200um，为保证探针尖端插入皮/黏膜下，又尽量不插入过深触碰神经和血管引起疼痛和流血，因此，传感探头部分一般根据测量位置皮层厚度，长度会控制在300-1000um。
S200、将所述探针阵列设置于探针衬底的第一端面。
具体地，探针衬底为PI(Polyimide，聚酰亚胺)衬底或者其他高分子绝缘衬底。
S300、将导线通过导管内部后与所述探针阵列连接。
具体地，每一根探针都具有独立的传感功能，因此每一个单独功能探针的导电功能部位 均有导线与之相连，导线与探针的连接采用焊接或者银浆连接的方式，连接点采用派瑞林或者强力胶封装固定。
当检测装置还包括弹性单元时，在医用微创手术导管管口探针加入一个弹性单元，如气压球或弹簧等，该弹性单元的一端需与探针阵列衬底固定相连。由于探针阵列的导线需要通过导管伸出，因此，该弹性单元在固定前需要预留出一定位置用于通过走线。
当检测装置还包括药物释放单元时，药物释放单元采用空心探针，每一个空心给药探针的内部均有一个微流管道与之固定，微流管道与空心探针直接采用强力胶封装固定露出微流管口即可。
当检测装置还包括电刺激电极时，每一个单独电刺激电极的导电功能部位均有导线与之相连，导线与电刺激电极的连接采用焊接或者银浆连接的方式，连接点采用派瑞林或者强力胶封装固定。
S400、将所述探针衬底密封贴合在所述导管的一端管口。
具体地，将集成的探针阵列衬与手术导管贴合：先将导线和微流管道置于手术导管内部，走线从弹性单元预留的通道伸出并固定，探针阵列衬底与弹性单元通过强力胶粘合固定，再与手术管道的管壁进行封装黏合(可采用PDMS等生物相容性较好，且韧性良好的材料封装)，保证管道与探针衬底的良好贴合和气密性。最后将伸出手术导管外部的导线和微流管道与外部商用仪器相连，并配合腔镜使用即可，利用腔镜可将器件送入待测部位。如图6所示，6-1表示某种窥镜，6-2表示含多参数探针的微介入导管，6-3表示与窥镜联合使用的检测装置，6-4表示人体器官，如膀胱，通过窥镜6-1将检测装置6-3的含多参数探针的微介入导管6-2送入到膀胱6-4进行尿酸的检测。
可选地，所述碳管/Mxenes复合材料的制备方法如下：
将碳管和Mxenes按照预设含量溶于水或有机溶液中，并充分混合。
具体地，碳管/MXene具体的制备方法：碳管/MXene混合液的溶剂为水或IPA(异丙醇)等有机溶剂均可，用移液枪分别吸取一定量的碳管溶液和MXene溶液置于容器中，充分混合，配成的混合液中碳管的含量为1％-5％，MXene含量为0.5％-4％。
可选地，所述探针阵列的实心探针和空心探针，当所述探针阵列为空心探针，所述空心探针的制备方法如下：
通过3D打印高分子材料获得空心探针。其中，高分子材料包括树脂或红蜡等材料。
可选地，所述探针阵列的实心探针和空心探针，当所述探针阵列为实心探针，所述实心探针的制备方法如下：
通过激光切割金属材料获得实心探针。
具体地，当探针阵列为实心探针时，如由激光切割制备的金属探针，该金属探针直接焊接于PI衬底或者其他高分子绝缘衬底上，由于PI衬底可以直接由微加工制备多条独立走线且为柔性，因此可以直接分别连通每个实心金属探针和外部电路。通过分别在探针表面修饰含碳管/Mxenes复合材料的多种检测敏感物，构建具有多功能的传感阵列。给药释放单元可以单独利用金属空心针头焊接于PI衬底的给药孔，药物通过外部引入微管连通PI给药孔。
实施本发明实施例包括以下有益效果：本发明实施例中的碳管/Mxenes复合材料具有良好的生物相容性、较好的导电性、较高的比表面积且具有电子介体的功能，探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物；通过导管作为载体，在不损伤机体的前提下将探针阵列送到待检测部位，探针阵列借助探针的穿透性进入黏膜组织检测标志物；从而实现微创、快速及多功能的标志物检测。
以上是对本发明的较佳实施进行了具体说明，但本发明创造并不限于所述实施例，熟悉本领域的技术人员在不违背本发明精神的前提下还可做作出种种的等同变形或替换，这些等同的变形或替换均包含在本申请权利要求所限定的范围内。

Claims (9)

  1. 一种基于碳管/Mxenes的标志物检测装置，其特征在于，包括导管、设置于导管内的导线、与所述导管的一端管口密封贴合的探针衬底、设置于所述探针衬底的第一端面的探针阵列，所述导线用于连接所述探针阵列及外部设备，所述探针阵列修饰有含碳管/Mxenes复合材料的检测敏感物。
  2. 根据权利要求1所述的检测装置，其特征在于，所述检测装置还包括弹性单元，所述弹性单元的第一端面固定连接所述探针衬底的第二端面，所述弹性单元的第二端面固定连接推送模块。
  3. 根据权利要求1所述的检测装置，其特征在于，所述检测装置还包括设置于所述导管内的药物释放单元，所述药物释放单元包括空心探针和微流导管，所述空心探针设置于所述探针衬底的第一端面，所述微流导管的一端固定连接所述空心探针。
  4. 根据权利要求1所述的检测装置，其特征在于，所述检测装置还包括设置于所述导管内的电刺激电极，所述电刺激电极包括电极和导线，所述导线的一端固定连接所述电极。
  5. 根据权利要求1所述的检测装置，其特征在于，所述探针阵列的类型包括实心探针、空心探针、包衣探针或可溶性探针中的一种或多种。
  6. 一种基于碳管/Mxenes的标志物检测装置的制备方法，其特征在于，包括：
    制备探针阵列，并在所述探针阵列的表面或内部修饰含碳管/Mxenes复合材料的检测敏感物；
    将所述探针阵列设置于探针衬底的第一端面；
    将导线通过导管内部后与所述探针阵列连接；
    将所述探针衬底密封贴合在所述导管的一端管口。
  7. 根据权利要求6所述的制备方法，其特征在于，所述碳管/Mxenes复合材料的制备方法如下：
    将碳管和Mxenes按照预设含量溶于水或有机溶液中，并充分混合。
  8. 根据权利要求6所述的制备方法，其特征在于，所述探针阵列的实心探针和空心探针，当所述探针阵列为空心探针，所述空心探针的制备方法如下：
    通过3D打印高分子材料获得空心探针。
  9. 根据权利要求6所述的制备方法，其特征在于，所述探针阵列的实心探针和空心探针，当所述探针阵列为实心探针，所述实心探针的制备方法如下：
    通过激光切割金属材料获得实心探针。
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