WO2022027185A1 - Semiconductor coating having antimicrobial and measurement effects, preparation method therefor, and use thereof - Google Patents

Semiconductor coating having antimicrobial and measurement effects, preparation method therefor, and use thereof Download PDF

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WO2022027185A1
WO2022027185A1 PCT/CN2020/106595 CN2020106595W WO2022027185A1 WO 2022027185 A1 WO2022027185 A1 WO 2022027185A1 CN 2020106595 W CN2020106595 W CN 2020106595W WO 2022027185 A1 WO2022027185 A1 WO 2022027185A1
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semiconductor
current
substrate
semiconductor coating
microbial
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PCT/CN2020/106595
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French (fr)
Chinese (zh)
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王国敏
唐楷为
孟哲一
王怀雨
朱剑豪
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深圳先进技术研究院
香港城市大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
    • B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • 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

Definitions

  • the invention belongs to the field of biological detection, and in particular relates to a semiconductor coating with both anti-microbial and detection effects, and its use in anti-microbial and detection of microbial content.
  • Implantation surgery is one of the common clinical treatment options to improve the quality of life of patients, but a key factor leading to the failure of implantation surgery is bacterial infection.
  • Appropriate modification of the implant surface can achieve an antibacterial surface and effectively reduce the infection rate.
  • the antibacterial interface can realize real-time monitoring of the number of bacteria, it will bring great convenience to doctors to monitor the infection of patients in time.
  • Electron transfer is a common physical phenomenon that occurs at interfaces with potential differences, and studies have shown that electron transfer between materials and bacteria plays a key role in this type of antibacterial process. A small number of studies have shown that the surface of materials modified with charges can also rely on electron transfer for effective antibacterial properties. All of the above methods are advancing the development of antibacterial materials step by step (Wang, G. et al. An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging. Nat. Commun. 9, 2055 (2018). Wang , G. et al. Extracellular electron transfer from aerobic bacteria to Au-loaded TiO 2 semiconductor without light: a new bacteria-killing mechanism other than localized surface plasmon resonance or microbial fuel cells.
  • Effective antibacterial can be achieved through the surface design of implants, thereby improving the success rate of biomedical applications.
  • most of the current antibacterial materials are release surfaces, and the design has the following defects.
  • grafting antibiotics and antimicrobial peptides to the surface of the material will cause Severe bacterial resistance, and mutations in resistant strains can exacerbate clinical infections.
  • various peptide materials are prone to immune reaction with the body, which increases the risk of implantation failure.
  • release-type antimicrobial surfaces non-release antimicrobial surfaces that rely on physical action can reduce systemic side effects because of their local action, do not require the replenishment of antimicrobial substances, and achieve precise infection control at the implant site. .
  • the invention aims to design an antibacterial system that relies on electron transfer and can monitor the number of bacteria in real time.
  • a bacterial current is generated due to the interface potential difference.
  • the magnitude of the current can reflect the number of bacteria, and the bacterial current At the same time, it can interfere with the physiological activities of bacteria to achieve a precise non-release antibacterial process.
  • This clean and environmentally friendly antibacterial system overcomes the systemic side effects of existing release-type antibacterial surfaces and the shortcomings of requiring replenishment of antibacterial substances.
  • the real-time monitoring function is helpful for doctors to understand the infection status in real time and take corresponding measures in a timely manner.
  • the present invention includes two parts. First design a semiconductor coating on the surface of the implant, then contact the bacteria with the coating, and connect the entire system to an electrochemical workstation or a microcurrent meter.
  • the magnitude of the current can reflect the number of bacteria, and the bacterial current can be used in a short period of time. Interfering with the electron transfer of the bacterial respiratory chain and inhibiting its growth and reproduction.
  • One aspect of the present invention provides a semiconductor coating that is anti-microbial and can self-measure the number of microorganisms.
  • the semiconductor coating is in situ generated on a substrate. Titanium dioxide nanomaterial arrays, silicon arrays, etc.
  • the surface of the semiconductor nanoarray also includes the modification of metal nanoparticles, preferably, the metal nanoparticles are selected from gold nanoparticles, silver nanoparticles, platinum nanoparticles, palladium nanoparticles and the like.
  • the substrate is selected from metal substrates and non-metallic substrates;
  • the metal substrate is selected from titanium substrates, magnesium substrates, aluminum substrates, and the like; the non-metallic substrates are selected from silicon substrates and the like.
  • the nanomaterial size of the semiconductor nanoarray is 10-500 nm, preferably 80-150 nm.
  • the method for in-situ generation of semiconductor nanoarrays by the semiconductor coating on the substrate is: 1) forming epoxy groups on the surface of the substrate; Generate semiconductor nanoarrays on the substrate.
  • the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy group.
  • a silane coupling agent preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane
  • the method of generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ring ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of hexamethylenetetramine and zinc acetate hexahydrate.
  • the method for modifying the metal nanoparticles on the surface of the semiconductor nano-array is to deposit the metal nanoparticles by a magnetron sputtering method.
  • the microorganisms are bacteria, fungi, viruses, preferably, the bacteria are Escherichia coli and Staphylococcus aureus.
  • the semiconductor nanoarray is a zinc oxide nanorod array, and the surface thereof is decorated with gold nanoparticles.
  • Another aspect of the present invention provides another method for preparing a semiconductor coating, comprising the steps of:
  • the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy group.
  • a silane coupling agent preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane
  • the method of generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ring ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of hexamethylenetetramine and zinc acetate hexahydrate.
  • the method for modifying the metal nanoparticles on the surface of the semiconductor nano-array is to deposit the metal nanoparticles by a magnetron sputtering method.
  • Yet another aspect of the present invention provides the use of the semiconductor coating, which provides the antimicrobial activity of the substrate while being capable of detecting the microbial content on the surface of the substrate.
  • the use of the semiconducting coating to provide the substrate antimicrobial activity is in an air environment, rather than a liquid environment.
  • Yet another aspect of the present invention provides an implant having the above-mentioned semiconductor coating.
  • Another aspect of the present invention provides a method for detecting microorganisms on the surface of an object, comprising the following steps:
  • the microbial liquid of known concentration is at least 3 microbial liquids of different known concentrations, preferably 3-6 microbial liquids of different known concentrations.
  • the concentration of the microorganism liquid of known concentration is 1-10 6 CFU mL -1 .
  • the microorganism is Escherichia coli
  • CFU is the concentration of E. coli.
  • CFU is the mixed concentration of Escherichia coli and Staphylococcus aureus.
  • the current reading time is within 5 minutes.
  • the device for detecting the current on the surface of the object is selected from an electrochemical workstation or a microcurrent meter.
  • the device for detecting the current on the surface of the object is a device capable of detecting a current of 100 ⁇ A or less.
  • the electrolyte used in the device for detecting the current on the surface of the object is selected from broth culture medium, physiological saline and phosphate buffered saline (PBS).
  • Another aspect of the present invention provides a system for controlling and detecting microorganisms on the surface of an object, which includes a current detection device, at least three microbial liquids with known concentrations, and forming the semiconductor coating described in any one of claims 1-3 on the surface of the object the material of the layer;
  • the device for detecting the current on the surface of the object is a device capable of detecting a current below 100 ⁇ A;
  • the material for forming the semiconductor coating according to any one of claims 1-3 on the surface of the object comprises silane coupling agent, zinc salt solution, sodium hydroxide, cyclohexamethylenetetramine, zinc acetate hexahydrate and metal nanoparticles.
  • the current generated by the interaction of the coating with the semiconductor characteristics of the present invention and the microorganisms can be used as a parameter for real-time monitoring of the number of microorganisms, and at the same time, it is a factor that interferes with the bacterial respiratory chain to achieve rapid non-release antibacterial.
  • the antibacterial system can perform antibacterial and real-time monitoring of the number of bacteria without interfering with the biocompatibility of the implant, and has the advantages of environmental protection and controllability.
  • the present invention relates to an antibacterial surface based on electron transfer with real-time monitoring of bacterial population. Compared with previous antibacterial surface designs, it has the following advantages:
  • the semiconductor coating provided by the present invention can achieve antimicrobial activity while providing the microbial contamination of the coating substrate product, and realizes the integration of antimicrobial and detection functions for the first time.
  • the semiconductor coating used in the present invention has a simple preparation process, high antibacterial efficiency, and can achieve high-efficiency inactivation in a short period of time. Because it utilizes physical properties for sterilization, the use of antibiotics is avoided, thereby avoiding antibiotic resistance caused by antibiotics. occur. And due to its limitations, inactivation is only limited to the surface of the semiconductor coating, which relies on contact with microorganisms. Compared with antibacterial surfaces that release ions or drugs, it can accurately kill microorganisms near the implanted surgical wound to achieve high-efficiency anti-infection avoidance. The use of antimicrobial peptides, antibiotics, etc., will produce systemic circulation after acting on the human body, resulting in potential safety hazards.
  • the present invention directly grows the semiconductor nano-array on the surface of the implant in situ, the surface modification is more firmly combined with the substrate, and the leakage of the modification does not occur.
  • metal oxides such as zinc oxide have antimicrobial activity, which is based on the antimicrobial activity of zinc ions, and the present invention does not utilize the antimicrobial activity of zinc ions, but is based on the current generated by microorganisms on the surface of the material. Therefore, the semiconductor coating of the present invention The antimicrobial activity is independent of the liquid environment, and antimicrobial activity can also be achieved in the air environment.
  • the present invention integrates the functions of monitoring microorganisms and anti-microbials, and can realize real-time monitoring of the infection status during the anti-infection process and prompt the user to take corresponding measures in time.
  • the monitoring and sterilization mechanism of the antibacterial system is based on the electron transfer between the material and the bacteria. Compared with the previous bifunctional surface that integrates traditional bacterial sensing devices and drug release, the working mechanism is simpler and the working system is more concise.
  • the semiconductor coating of the present invention can be combined with a wearable energy device, and can use autologous mechanical motion energy to monitor the number of bacteria and antibacterial.
  • the invention integrates the functions of monitoring bacteria and antibacterial, and can realize real-time monitoring of the infection status during the anti-infection process and prompt the user to take corresponding measures in time.
  • Figure 1 a Array of ZnO nanorods decorated with gold nanoparticles under scanning electron microscope.
  • Figure 1b shows the distribution of elements on the surface of the nano-gold-modified ZnO array.
  • Figure 2 Scatter plot of bacterial number and bacterial current and linear fit.
  • Fig. 3a The change curve of bacterial current within 1h of bacteria interacting with the material.
  • Figure 3b The antibacterial effect of bacteria and materials within 1 h.
  • Figure 4 Scatter diagram and linear fitting of bacterial number and bacterial current in the mixed bacterial solution composed of Escherichia coli and Staphylococcus aureus.
  • One aspect of the present invention provides a semiconductor coating that is anti-microbial and can self-measure the number of microorganisms.
  • the semiconductor coating is in situ generated on a substrate. Titanium dioxide nanomaterial arrays, silicon nanoarrays, etc.
  • the surface of the semiconductor nanoarray further includes modification of metal nanoparticles, preferably, the metal nanoparticles are selected from gold nanoparticles, silver nanoparticles, platinum nanoparticles, palladium nanoparticles and the like.
  • the substrate is selected from metal substrates and non-metallic substrates; preferably, the metal substrate is selected from titanium substrates, magnesium substrates, aluminum substrates, etc.; the non-metallic substrates are selected from silicon substrates Wait.
  • the nanomaterial size of the semiconductor nanoarray is 10-500 nm, preferably 80-150 nm.
  • the method for in-situ generation of semiconductor nanoarrays by the semiconductor coating on the substrate is: 1) forming epoxy groups on the surface of the substrate; The semiconductor nanoarrays are formed on the oxides.
  • the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy groups.
  • a silane coupling agent preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane
  • the method for generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of cyclohexamethylenetetramine and zinc acetate hexahydrate.
  • the method for modifying the metal nanoparticles on the surface of the semiconductor nanoarray is to deposit the metal nanoparticles by magnetron sputtering.
  • the microorganisms are bacteria, fungi and viruses, preferably, the bacteria are Escherichia coli and Staphylococcus aureus.
  • the semiconductor nanoarray is a zinc oxide nanorod array, and the surface thereof is decorated with gold nanoparticles.
  • Another aspect of the present invention provides a method for preparing a semiconductor coating, comprising the steps of:
  • the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy groups.
  • a silane coupling agent preferably ⁇ -(2,3-glycidoxy)propyltrimethoxysilane.
  • the epoxy group can make the semiconductor nano-array and the substrate contact more closely, thereby enhancing the electron transfer process, which is beneficial to improve the antibacterial effect.
  • the method for generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of cyclohexamethylenetetramine and zinc acetate hexahydrate.
  • the method for modifying the metal nanoparticles on the surface of the semiconductor nanoarray is to deposit the metal nanoparticles by magnetron sputtering.
  • Yet another aspect of the present invention provides the use of the semiconductor coating, which provides the antimicrobial activity of the substrate while being capable of detecting the microbial content on the surface of the substrate.
  • Yet another aspect of the present invention provides an implant having the above-mentioned semiconductor coating.
  • Another aspect of the present invention provides a method for detecting microorganisms on the surface of an object, comprising the following steps:
  • the microbial liquid of known concentration is at least 3 microbial liquids of different known concentrations, preferably 3-6 microbial liquids of different known concentrations.
  • the concentration of the microbial liquid of known concentration is 1-10 6 CFU mL -1 .
  • the current reading time is within 5 minutes.
  • the device for detecting the current on the surface of the object is selected from an electrochemical workstation or a micro-galvanometer.
  • the device for detecting the current on the surface of the object is a device capable of detecting a current of less than 100 ⁇ A.
  • the electrolyte used in the device for detecting the current on the surface of the object is selected from broth culture medium, physiological saline and phosphate buffered saline (PBS).
  • PBS phosphate buffered saline
  • a method for establishing microbial concentration assessment on an object surface comprising the following steps:
  • the microorganism liquid of known concentration is mixed microorganism liquid, and the microorganism liquid of known concentration is 100 kinds of microorganism liquid of known concentration.
  • the microorganism liquid of known concentration is more than 1000 kinds of microorganism liquid of different known concentration.
  • a coating composed of semiconductors is first designed, and then the material is interacted with bacteria, and an electrochemical workstation or a microcurrent meter is connected to test the interface current.
  • the number of bacteria can be known by the magnitude of the current. In a short time, it can interfere with the electron transfer of the bacterial respiratory chain and inhibit its growth and reproduction.
  • the titanium alloy was processed into a rectangular parallelepiped with a length, width and height of 30mm, 30mm and 0.5mm, polished and ground, and then ultrasonically cleaned in acetone, ethanol and water for 10 minutes, and dried with nitrogen for use. Soak the above titanium alloy material in NaOH aqueous solution (10M) for 2h, and react with ⁇ -(2,3-glycidoxy)propyltrimethoxysilane KH-560 (2%v/v) for 10h to form epoxy function group.
  • the above-mentioned titanium alloy loaded with nano-gold-modified zinc oxide nanorods was connected to the electrochemical workstation, and bacterial liquid was added on the surface of the material.
  • the bacterial liquid concentration was 1-10 6 CFU mL -1 , and the bacterial current was recorded and the bacteria were drawn.
  • Bacterial liquid was dropped onto the surface of the above materials, the concentration of the bacterial liquid was 1-10 6 CFU mL -1 , the material was interacted with the bacteria for a certain time (1-180 min), and the bacteria were coated and tested for physiological activity to verify the antibacterial effect.
  • the titanium alloy was processed into a rectangular parallelepiped with a length, width and height of 30mm, 30mm, and 0.5mm, polished and ground, and then ultrasonically cleaned in acetone, ethanol, and water for 10 minutes, and dried with nitrogen for use.
  • the above titanium alloy materials were soaked in NaOH aqueous solution (10M) for 2h, and reacted with KH-560 (2%v/v) for 10h to form epoxy functional groups. Then prepare a methanol solution of Zn(CH 3 COO) 2 ⁇ 2H 2 O (10 mM) and NaOH (30 mM), pipette 10 ⁇ L drop onto the sample surface and treat at 120° C. for 5 min and repeat three times to prepare a seed layer.
  • the above samples were placed in a mixed aqueous solution of cyclohexamethylenetetramine (50 mM) and zinc acetate hexahydrate (50 mM), and hydrothermally treated at 96 °C for 10-12 h to generate ZnO nanorod semiconductors.
  • the sample was rinsed with 5 mL of water for 2 min and blown dry with nitrogen.
  • Gold nanoparticles were then deposited onto the nanorods by magnetron sputtering to enhance the electron transport capability of the semiconductor.
  • the microscopic morphology of the sample surface was observed by scanning electron microscope, and the microscopic morphology shown in Fig. 1a was obtained. It can be seen from the figure that the diameter of the zinc oxide nanorods is 100 nm, and the gold nanoparticles are attached to the nanorods or filled between the nanorods (as shown by the arrows in Figure 1).
  • Elemental content analysis was performed on the surface of the sample treated in Example 1.
  • the energy spectrum (Fig. 1b) shows that zinc, oxygen, gold, and titanium elements are uniformly distributed on the surface of the sample, indicating that the zinc oxide coating and the gold nanoparticles are uniformly distributed.
  • Example 2 The samples obtained in Example 1 were reacted with different concentrations of Escherichia coli (concentrations of 1, 10 3 , 10 5 and 10 6 CFU mL -1 ) to make a scatter plot of bacterial number and bacterial current, and fit. The results are shown in Figure 2.
  • the logarithmic number of bacteria was linearly related to bacterial current with a correlation coefficient as high as 0.98. It shows that the current obtained by the detection has a linear relationship with the bacterial content, and the bacterial content can be predicted by the current detection.
  • Example 1 The sample obtained in Example 1 was acted on with different concentrations of Escherichia coli and Staphylococcus aureus mixed bacterial solution (concentrations were 1, 10 3 , 10 5 and 10 6 CFU mL -1 ) to make a scatter plot of bacterial number and bacterial current , to fit.
  • concentrations were 1, 10 3 , 10 5 and 10 6 CFU mL -1
  • the results are shown in Figure 4.
  • the logarithm of the mixed bacterial count was linearly related to the bacterial current with a correlation coefficient as high as 0.96. It shows that the current obtained by the detection has a linear relationship with the mixed bacterial content, and the number of bacteria in the mixed bacterial solution of various bacterial species can be predicted by current detection.

Abstract

The present invention relates to a semiconductor coating having antimicrobial and measurement effects, a preparation method therefor, and a use thereof, and specifically disclosed is an antimicrobial semiconductor coating that can self-measure microbe quantity, the semiconductor coating is on an in situ generated semiconductor nano-array on a generated epoxy group on a substrate, where the semiconductor nano-array is selected from a zinc oxide nanomaterial array, a titanium dioxide nanomaterial array, or a silicon array; and a surface of the semiconductor nano-array further comprises a metal nanoparticle modification. Also disclosed is a use of a semiconductor coating, the semiconductor coating provides both substrate antimicrobial activity and is able to measure microbial content on a surface of the substrate. The present invention integrates bacterial monitoring and antibacterial functions as one, and can be implemented when fighting an infection for performing real-time monitoring of the state of an infection and notifying a user to carry out corresponding measures in a timely manner.

Description

一种抗微生物兼具检测效果的半导体涂层及其制备方法和用途A kind of semiconductor coating with anti-microbial and detection effect, preparation method and use thereof 技术领域technical field
本发明属于生物检测领域，具体涉及抗微生物兼具检测效果的半导体涂层及其抗微生物以及检测微生物含量中的用途。The invention belongs to the field of biological detection, and in particular relates to a semiconductor coating with both anti-microbial and detection effects, and its use in anti-microbial and detection of microbial content.
背景技术Background technique
植入手术是临床常见的改善患者生活质量的治疗方案之一，但是导致植入手术失败的一个关键因素是细菌的感染，将植入体表面进行适当修饰可实现抗菌表面从而有效降低感染率。与此同时，如果抗菌界面可以实现对细菌数量的实时监测，会给医生及时监测病人感染情况带来极大的便利。Implantation surgery is one of the common clinical treatment options to improve the quality of life of patients, but a key factor leading to the failure of implantation surgery is bacterial infection. Appropriate modification of the implant surface can achieve an antibacterial surface and effectively reduce the infection rate. At the same time, if the antibacterial interface can realize real-time monitoring of the number of bacteria, it will bring great convenience to doctors to monitor the infection of patients in time.
电子传递是一种发生于具有电势差的界面的常见的物理现象，研究表明材料与细菌之间的电子传递在该类抗菌过程中起着关键作用。少部分研究表明修饰有电荷的材料表面也可以依赖于电子传递而有效抗菌。以上这些方法都在一步步推进抗菌材料的发展(Wang,G.et al.An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging.Nat.Commun.9,2055(2018).Wang,G.et al.Extracellular electron transfer from aerobic bacteria to Au-loaded TiO 2 semiconductor without light:a new bacteria-killing mechanism other than localized surface plasmon resonance or microbial fuel cells.ACS Appl.Mater.Interfaces 8,24509-24516(2016).Chernousova,S.,Epple,M.Silver as antibacterial agent:ion,nanoparticle,and metal.Angew.Chem.Int.Ed.52,1636-1653(2013))。 Electron transfer is a common physical phenomenon that occurs at interfaces with potential differences, and studies have shown that electron transfer between materials and bacteria plays a key role in this type of antibacterial process. A small number of studies have shown that the surface of materials modified with charges can also rely on electron transfer for effective antibacterial properties. All of the above methods are advancing the development of antibacterial materials step by step (Wang, G. et al. An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging. Nat. Commun. 9, 2055 (2018). Wang , G. et al. Extracellular electron transfer from aerobic bacteria to Au-loaded TiO 2 semiconductor without light: a new bacteria-killing mechanism other than localized surface plasmon resonance or microbial fuel cells. ACS Appl.Mater.Interfaces 8,24509-24516 (2016). Chernousova, S., Epple, M. Silver as antibacterial agent:ion, nanoparticle, and metal. Angew. Chem. Int. Ed. 52, 1636-1653 (2013)).
通过对植入体的表面设计可以实现有效抗菌因而提高其生物医学应用的成功率，但是目前的抗菌材料大都为释放型表面，设计有以下缺陷，例如向材料表面接枝抗生素以及抗菌肽会引起严重的细菌耐药性，而耐药菌株的突变会加重临床感染。同时各种肽类材料易与机体发生免疫反应而增加了植入手术的失败的风险。与释放型抗菌表面相比，依赖于物理作用的非释放型抗菌表面因其可以局部作用从而减少全身性副作用的产生，同时不需要抗菌物质的再补充以及实现对植入部位的精准感染防控。尽管集抗菌检测于一体的表面可以为使用者提供极大便利，但目前的抗菌表面大都只具有单一抗菌功能而缺乏实时监测细菌数量的功 能，仅有的可同时监测细菌的抗菌材料由传统细菌传感器和抗生素机械组成，结构冗杂且效率较低。Effective antibacterial can be achieved through the surface design of implants, thereby improving the success rate of biomedical applications. However, most of the current antibacterial materials are release surfaces, and the design has the following defects. For example, grafting antibiotics and antimicrobial peptides to the surface of the material will cause Severe bacterial resistance, and mutations in resistant strains can exacerbate clinical infections. At the same time, various peptide materials are prone to immune reaction with the body, which increases the risk of implantation failure. Compared with release-type antimicrobial surfaces, non-release antimicrobial surfaces that rely on physical action can reduce systemic side effects because of their local action, do not require the replenishment of antimicrobial substances, and achieve precise infection control at the implant site. . Although the surface that integrates antibacterial detection can provide users with great convenience, most of the current antibacterial surfaces only have a single antibacterial function and lack the function of monitoring the number of bacteria in real time. The only antibacterial materials that can simultaneously monitor bacteria are traditional bacteria. The sensor and antibiotic machinery are composed of complex structure and low efficiency.
发明内容SUMMARY OF THE INVENTION
本发明旨在设计一种依赖于电子传递的可实时监测细菌数量的抗菌体系，半导体组成的涂层在与细菌接触时因界面电势差而产生细菌电流，电流的大小可以反映细菌的数量，细菌电流同时可以干扰细菌的生理活动而实现精准的非释放型抗菌过程。这一清洁环保的抗菌体系克服了现有释放型抗菌表面的全身副作用以及需要抗菌物质再补充的缺点。同时，实时监测功能利于医生实时了解感染状况而及时采取相应措施。The invention aims to design an antibacterial system that relies on electron transfer and can monitor the number of bacteria in real time. When the coating composed of semiconductors is in contact with bacteria, a bacterial current is generated due to the interface potential difference. The magnitude of the current can reflect the number of bacteria, and the bacterial current At the same time, it can interfere with the physiological activities of bacteria to achieve a precise non-release antibacterial process. This clean and environmentally friendly antibacterial system overcomes the systemic side effects of existing release-type antibacterial surfaces and the shortcomings of requiring replenishment of antibacterial substances. At the same time, the real-time monitoring function is helpful for doctors to understand the infection status in real time and take corresponding measures in a timely manner.
本发明包括两部分内容。首先在植入体表面设计半导体涂层，然后将细菌与涂层接触，并将整个体系接入电化学工作站或微电流计，电流的大小可以反映细菌的数量，而细菌电流可以在短时间内实现对细菌呼吸链电子传递的干扰而抑制其生长繁殖。The present invention includes two parts. First design a semiconductor coating on the surface of the implant, then contact the bacteria with the coating, and connect the entire system to an electrochemical workstation or a microcurrent meter. The magnitude of the current can reflect the number of bacteria, and the bacterial current can be used in a short period of time. Interfering with the electron transfer of the bacterial respiratory chain and inhibiting its growth and reproduction.
本发明一个方面提供了一种抗微生物且能自测微生物数量的半导体涂层，所述半导体涂层在基底上原位生成的半导体纳米阵列，所述半导体纳米阵列选自氧化锌纳米材料阵列、二氧化钛纳米材料阵列、硅阵列等。One aspect of the present invention provides a semiconductor coating that is anti-microbial and can self-measure the number of microorganisms. The semiconductor coating is in situ generated on a substrate. Titanium dioxide nanomaterial arrays, silicon arrays, etc.
在本发明的技术方案中，半导体纳米阵列表面还包括金属纳米颗粒的修饰，优选地，所述的金属纳米颗粒选自金纳米颗粒、银纳米颗粒、铂纳米颗粒、钯纳米颗粒等。In the technical solution of the present invention, the surface of the semiconductor nanoarray also includes the modification of metal nanoparticles, preferably, the metal nanoparticles are selected from gold nanoparticles, silver nanoparticles, platinum nanoparticles, palladium nanoparticles and the like.
在本发明的技术方案中，所述的基底选自金属基底、非金属基底；In the technical solution of the present invention, the substrate is selected from metal substrates and non-metallic substrates;
优选地，所述金属基底选自钛基底、镁基底、铝基底等；所述非金属基底选自硅基底等。Preferably, the metal substrate is selected from titanium substrates, magnesium substrates, aluminum substrates, and the like; the non-metallic substrates are selected from silicon substrates and the like.
在本发明的技术方案中，半导体纳米阵列的纳米材料尺寸为10-500nm，优选为80-150nm。In the technical solution of the present invention, the nanomaterial size of the semiconductor nanoarray is 10-500 nm, preferably 80-150 nm.
在本发明的技术方案中，所述半导体涂层在基底上原位生成的半导体纳米阵列的方法为：1)在基底表面形成环氧基；2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列。In the technical solution of the present invention, the method for in-situ generation of semiconductor nanoarrays by the semiconductor coating on the substrate is: 1) forming epoxy groups on the surface of the substrate; Generate semiconductor nanoarrays on the substrate.
在本发明的技术方案中，在基底表面形成环氧基的方法为将基底与硅烷偶联 剂，优选为γ―(2,3-环氧丙氧)丙基三甲氧基硅烷进行反应，获得环氧基。In the technical solution of the present invention, the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably γ-(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy group.
在本发明的技术方案中，以水热法在环氧基上生成氧化锌半导体纳米阵列的方法为锌盐溶液和氢氧化钠的醇溶液在100-150℃下反应制备种子层；然后加入环六亚甲基四胺和六水合醋酸锌的混合水溶液中水热处理生成氧化锌半导体纳米阵列。In the technical scheme of the present invention, the method of generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ring ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of hexamethylenetetramine and zinc acetate hexahydrate.
在本发明的技术方案中，半导体纳米阵列表面上金属纳米颗粒的修饰方法为以磁控溅射方法沉积金属纳米颗粒。In the technical solution of the present invention, the method for modifying the metal nanoparticles on the surface of the semiconductor nano-array is to deposit the metal nanoparticles by a magnetron sputtering method.
在本发明的技术方案中，所述的微生物为细菌、真菌、病毒、优选地，所述的细菌为大肠杆菌、金黄色葡萄球菌。In the technical scheme of the present invention, the microorganisms are bacteria, fungi, viruses, preferably, the bacteria are Escherichia coli and Staphylococcus aureus.
在本发明一个优选的技术方案中，所述的半导体纳米阵列为氧化锌纳米棒阵列，且其表面修饰有金纳米颗粒。In a preferred technical solution of the present invention, the semiconductor nanoarray is a zinc oxide nanorod array, and the surface thereof is decorated with gold nanoparticles.
本发明另一个方面提供另一种半导体涂层的制备方法，其包括如下步骤：Another aspect of the present invention provides another method for preparing a semiconductor coating, comprising the steps of:
1)在基底表面形成环氧基；1) form epoxy groups on the surface of the substrate;
2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列；2) generating semiconductor nanoarrays on epoxy groups by hydrothermal method or anodizing method;
3)在半导体纳米阵列表面上修饰金属纳米颗粒。3) Modification of metal nanoparticles on the surface of semiconductor nanoarrays.
在本发明的技术方案中，在基底表面形成环氧基的方法为将基底与硅烷偶联剂，优选为γ―(2,3-环氧丙氧)丙基三甲氧基硅烷进行反应，获得环氧基。In the technical solution of the present invention, the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably γ-(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy group.
在本发明的技术方案中，以水热法在环氧基上生成氧化锌半导体纳米阵列的方法为锌盐溶液和氢氧化钠的醇溶液在100-150℃下反应制备种子层；然后加入环六亚甲基四胺和六水合醋酸锌的混合水溶液中水热处理生成氧化锌半导体纳米阵列。In the technical scheme of the present invention, the method of generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ring ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of hexamethylenetetramine and zinc acetate hexahydrate.
在本发明的技术方案中，半导体纳米阵列表面上金属纳米颗粒的修饰方法为以磁控溅射方法沉积金属纳米颗粒。In the technical solution of the present invention, the method for modifying the metal nanoparticles on the surface of the semiconductor nano-array is to deposit the metal nanoparticles by a magnetron sputtering method.
本发明再一个方面提供所述半导体涂层的用途，所述半导体涂层提供基底抗微生物活性的同时能够检测基底表面微生物含量。Yet another aspect of the present invention provides the use of the semiconductor coating, which provides the antimicrobial activity of the substrate while being capable of detecting the microbial content on the surface of the substrate.
在本发明的技术方案中，所述半导体涂层的用途中提供基底抗微生物活性为在空气环境中，而非液体环境中。In the technical solution of the present invention, the use of the semiconducting coating to provide the substrate antimicrobial activity is in an air environment, rather than a liquid environment.
本发明再一个方面提供了一种植入物，所述植入物具有上述半导体涂层。Yet another aspect of the present invention provides an implant having the above-mentioned semiconductor coating.
本发明再一个方面提供了一种物体表面微生物的检测方法，其包括以下步 骤：Another aspect of the present invention provides a method for detecting microorganisms on the surface of an object, comprising the following steps:
1)在物体表面生成上述半导体涂层；1) generating the above-mentioned semiconductor coating on the surface of the object;
2)将已知浓度的微生物液体涂覆在上述包含半导体涂层的物体表面，并检测该表面的电流，并绘制电流与微生物浓度之间的曲线；2) Coat the surface of the above-mentioned object containing the semiconductor coating with a microorganism liquid of known concentration, and detect the current on the surface, and draw a curve between the current and the concentration of microorganisms;
3)检测物体表面的电流，根据上述曲线计算物体表面微生物数量。3) Detect the current on the surface of the object, and calculate the number of microorganisms on the surface of the object according to the above curve.
在本发明的技术方案中，所述的检测方法中，已知浓度的微生物液体为至少3个不同已知浓度的微生物液体，优选为3-6个不同已知浓度的微生物液体。In the technical solution of the present invention, in the detection method, the microbial liquid of known concentration is at least 3 microbial liquids of different known concentrations, preferably 3-6 microbial liquids of different known concentrations.
在本发明的技术方案中，所述的检测方法中，已知浓度的微生物液体的浓度为1-10 6CFU mL -1。 In the technical solution of the present invention, in the detection method, the concentration of the microorganism liquid of known concentration is 1-10 6 CFU mL -1 .
在本发明的优选技术方案中，所述的微生物为大肠杆菌，电流与大肠杆菌浓度之间的关系为电流(μA)＝-1.43+0.56*log CFU。其中CFU为大肠杆菌浓度。In a preferred technical solution of the present invention, the microorganism is Escherichia coli, and the relationship between the current and the concentration of Escherichia coli is current (μA)=-1.43+0.56*log CFU. where CFU is the concentration of E. coli.
在本发明的优选技术方案中，所述的微生物为大肠杆菌与金黄色葡萄球菌，电流与大肠杆菌浓度之间的关系为电流(μA)＝0.179+0.290*log CFU。其中CFU为大肠杆菌与金黄色葡萄球菌混合浓度。In a preferred technical solution of the present invention, the microorganisms are Escherichia coli and Staphylococcus aureus, and the relationship between the current and the concentration of Escherichia coli is current (μA)=0.179+0.290*log CFU. Wherein CFU is the mixed concentration of Escherichia coli and Staphylococcus aureus.
在本发明的技术方案中，所述的检测方法中，检测物体表面的电流时，电流读取时间在5min以内。In the technical solution of the present invention, in the detection method, when the current on the surface of the object is detected, the current reading time is within 5 minutes.
在本发明的技术方案中，检测物体表面的电流的设备选自电化学工作站或微电流计。In the technical solution of the present invention, the device for detecting the current on the surface of the object is selected from an electrochemical workstation or a microcurrent meter.
在本发明的技术方案中，检测物体表面的电流的设备为能够检测100μA以下电流的设备。In the technical solution of the present invention, the device for detecting the current on the surface of the object is a device capable of detecting a current of 100 μA or less.
在本发明的技术方案中，检测物体表面的电流的设备中所使用的电解液选自肉汤培养基、生理盐水以及磷酸盐缓冲液(PBS)。In the technical solution of the present invention, the electrolyte used in the device for detecting the current on the surface of the object is selected from broth culture medium, physiological saline and phosphate buffered saline (PBS).
本发明再一个方面提供了一种物体表面微生物控制和检测***，其包括电流检测设备、至少3个已知浓度的微生物液体以及在物体表面形成权利要求1-3任一项所述的半导体涂层的材料；Another aspect of the present invention provides a system for controlling and detecting microorganisms on the surface of an object, which includes a current detection device, at least three microbial liquids with known concentrations, and forming the semiconductor coating described in any one of claims 1-3 on the surface of the object the material of the layer;
优选地，检测物体表面的电流的设备为能够检测为100μA以下电流的设备；Preferably, the device for detecting the current on the surface of the object is a device capable of detecting a current below 100 μA;
优选地，在物体表面形成权利要求1-3任一项所述的半导体涂层的材料包括硅烷偶联剂、锌盐溶液、氢氧化钠、环六亚甲基四胺、六水合醋酸锌和金属纳米颗粒。Preferably, the material for forming the semiconductor coating according to any one of claims 1-3 on the surface of the object comprises silane coupling agent, zinc salt solution, sodium hydroxide, cyclohexamethylenetetramine, zinc acetate hexahydrate and metal nanoparticles.
本发明半导体特性的涂层与微生物相互作用而产生的电流既可以作为实时监测微生物数量的参数，同时又是对细菌呼吸链的干扰而实现快速非释放型抗菌的因素。该抗菌体系可以在不干扰植入体生物相容性前提下进行抗菌和对细菌数量进行实时监控，具有环保可控的优势。The current generated by the interaction of the coating with the semiconductor characteristics of the present invention and the microorganisms can be used as a parameter for real-time monitoring of the number of microorganisms, and at the same time, it is a factor that interferes with the bacterial respiratory chain to achieve rapid non-release antibacterial. The antibacterial system can perform antibacterial and real-time monitoring of the number of bacteria without interfering with the biocompatibility of the implant, and has the advantages of environmental protection and controllability.
本发明涉及一种基于电子传递的同时具有实时监测细菌数量的抗菌表面。与以往抗菌表面设计相比具有以下优点：The present invention relates to an antibacterial surface based on electron transfer with real-time monitoring of bacterial population. Compared with previous antibacterial surface designs, it has the following advantages:
1、本发明提供的半导体涂层能够实现抗微生物活性的同时提供该涂层基底产品的微生物污染情况，首次实现了集抗微生物和检测功能于一体。1. The semiconductor coating provided by the present invention can achieve antimicrobial activity while providing the microbial contamination of the coating substrate product, and realizes the integration of antimicrobial and detection functions for the first time.
2、本发明采用的半导体涂层制备工艺简单，抗菌效率高，能够实现短时间内的高效灭活，由于其利用物理特性灭菌，避免了抗生素的使用，进而避免了抗生素引起的耐药性发生。且由于其具有局限性，灭活仅局限在半导体涂层表面，其依赖于与微生物的接触，与释放离子或药物的抗菌表面相比可以精准杀死植入手术创口附近微生物达到高效抗感染避免了使用抗菌肽、抗生素等作用于人体后会产生全身循环，因而产生安全隐患。2. The semiconductor coating used in the present invention has a simple preparation process, high antibacterial efficiency, and can achieve high-efficiency inactivation in a short period of time. Because it utilizes physical properties for sterilization, the use of antibiotics is avoided, thereby avoiding antibiotic resistance caused by antibiotics. occur. And due to its limitations, inactivation is only limited to the surface of the semiconductor coating, which relies on contact with microorganisms. Compared with antibacterial surfaces that release ions or drugs, it can accurately kill microorganisms near the implanted surgical wound to achieve high-efficiency anti-infection avoidance. The use of antimicrobial peptides, antibiotics, etc., will produce systemic circulation after acting on the human body, resulting in potential safety hazards.
3、本发明直接在植入体表面原位生长半导体纳米阵列，表面修饰与基底结合更牢，不会发生修饰物的泄露。3. The present invention directly grows the semiconductor nano-array on the surface of the implant in situ, the surface modification is more firmly combined with the substrate, and the leakage of the modification does not occur.
4、通常金属氧化物例如氧化锌具有抗微生物活性，是基于锌离子的抗菌活性，而本发明并非利用锌离子的抗菌活性，而是基于材料表面微生物产生的电流，因此，本发明的半导体涂料抗微生物活性不依赖于液体环境，而在空气环境中也可以实现抗微生物活性。4. Usually metal oxides such as zinc oxide have antimicrobial activity, which is based on the antimicrobial activity of zinc ions, and the present invention does not utilize the antimicrobial activity of zinc ions, but is based on the current generated by microorganisms on the surface of the material. Therefore, the semiconductor coating of the present invention The antimicrobial activity is independent of the liquid environment, and antimicrobial activity can also be achieved in the air environment.
5、本发明集监测微生物和抗微生物功能于一体，可实现在抗感染过程中对感染状况进行实时监测并提示使用者及时采取相应措施。5. The present invention integrates the functions of monitoring microorganisms and anti-microbials, and can realize real-time monitoring of the infection status during the anti-infection process and prompt the user to take corresponding measures in time.
6、该抗菌体系监测及杀菌机理均基于材料与细菌之间的电子传递，与以往集传统细菌传感器件和药物释放于一体的双功能表面相比工作机理更为简单，工作体系更为简洁。6. The monitoring and sterilization mechanism of the antibacterial system is based on the electron transfer between the material and the bacteria. Compared with the previous bifunctional surface that integrates traditional bacterial sensing devices and drug release, the working mechanism is simpler and the working system is more concise.
7、本发明半导体涂层可以与可穿戴能源装置相结合，可利用自体机械运动能量监测细菌数量及抗菌。7. The semiconductor coating of the present invention can be combined with a wearable energy device, and can use autologous mechanical motion energy to monitor the number of bacteria and antibacterial.
本发明集监测细菌和抗菌功能于一体，可实现在抗感染过程中对感染状况进行实时监测并提示使用者及时采取相应措施。The invention integrates the functions of monitoring bacteria and antibacterial, and can realize real-time monitoring of the infection status during the anti-infection process and prompt the user to take corresponding measures in time.
附图说明Description of drawings
图1a扫描电子显微镜下纳米金修饰的氧化锌纳米棒阵列。Figure 1a Array of ZnO nanorods decorated with gold nanoparticles under scanning electron microscope.
图1b能谱图谱显示纳米金修饰的氧化锌阵列表面元素分布情况。Figure 1b shows the distribution of elements on the surface of the nano-gold-modified ZnO array.
图2细菌数量与细菌电流散点图以及线性拟合。Figure 2. Scatter plot of bacterial number and bacterial current and linear fit.
图3a细菌与材料作用1h内细菌电流变化曲线。Fig. 3a The change curve of bacterial current within 1h of bacteria interacting with the material.
图3b细菌与材料作用1h内抗菌效果。Figure 3b The antibacterial effect of bacteria and materials within 1 h.
图4由大肠杆菌与金黄色葡萄球菌组成的混合菌液细菌数量与细菌电流散点图及线性拟合。Figure 4. Scatter diagram and linear fitting of bacterial number and bacterial current in the mixed bacterial solution composed of Escherichia coli and Staphylococcus aureus.
具体实施方式detailed description
为了使本发明的上述目的、特征和优点能够更加明显易懂，下面对本发明的具体实施方式做详细的说明，但不能理解为对本发明的可实施范围的限定。In order to make the above objects, features and advantages of the present invention more clearly understood, the specific embodiments of the present invention will be described in detail below, but should not be construed as limiting the scope of the present invention.
本发明一个方面提供了一种抗微生物且能自测微生物数量的半导体涂层，所述半导体涂层在基底上原位生成的半导体纳米阵列，所述半导体纳米阵列选自氧化锌纳米材料阵列、二氧化钛纳米材料阵列、硅纳米阵列等。One aspect of the present invention provides a semiconductor coating that is anti-microbial and can self-measure the number of microorganisms. The semiconductor coating is in situ generated on a substrate. Titanium dioxide nanomaterial arrays, silicon nanoarrays, etc.
在本发明一些具体实施例中，半导体纳米阵列表面还包括金属纳米颗粒的修饰，优选地，所述的金属纳米颗粒选自金纳米颗粒、银纳米颗粒、铂纳米颗粒、钯纳米颗粒等。In some specific embodiments of the present invention, the surface of the semiconductor nanoarray further includes modification of metal nanoparticles, preferably, the metal nanoparticles are selected from gold nanoparticles, silver nanoparticles, platinum nanoparticles, palladium nanoparticles and the like.
在本发明一些具体实施例中，所述的基底选自金属基底、非金属基底；优选地，所述金属基底选自钛基底、镁基底、铝基底等；所述非金属基底选自硅基底等。In some specific embodiments of the present invention, the substrate is selected from metal substrates and non-metallic substrates; preferably, the metal substrate is selected from titanium substrates, magnesium substrates, aluminum substrates, etc.; the non-metallic substrates are selected from silicon substrates Wait.
在本发明一些具体实施例中，半导体纳米阵列的纳米材料尺寸为10-500nm，优选为80-150nm。In some specific embodiments of the present invention, the nanomaterial size of the semiconductor nanoarray is 10-500 nm, preferably 80-150 nm.
在本发明一些具体实施例中，所述半导体涂层在基底上原位生成的半导体纳米阵列的方法为：1)在基底表面形成环氧基；2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列。In some specific embodiments of the present invention, the method for in-situ generation of semiconductor nanoarrays by the semiconductor coating on the substrate is: 1) forming epoxy groups on the surface of the substrate; The semiconductor nanoarrays are formed on the oxides.
在本发明一些具体实施例中，在基底表面形成环氧基的方法为将基底与硅烷偶联剂，优选为γ―(2,3-环氧丙氧)丙基三甲氧基硅烷进行反应，获得环氧基。In some specific embodiments of the present invention, the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably γ-(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy groups.
在本发明一些具体实施例中，以水热法在环氧基上生成氧化锌半导体纳米阵列的方法为锌盐溶液和氢氧化钠的醇溶液在100-150℃下反应制备种子层；然后加入环六亚甲基四胺和六水合醋酸锌的混合水溶液中水热处理生成氧化锌半导体纳米阵列。In some specific embodiments of the present invention, the method for generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of cyclohexamethylenetetramine and zinc acetate hexahydrate.
在本发明一些具体实施例中，半导体纳米阵列表面上金属纳米颗粒的修饰方法为以磁控溅射方法沉积金属纳米颗粒。In some specific embodiments of the present invention, the method for modifying the metal nanoparticles on the surface of the semiconductor nanoarray is to deposit the metal nanoparticles by magnetron sputtering.
在本发明一些具体实施例中，所述的微生物为细菌、真菌、病毒，优选地，所述的细菌为大肠杆菌、金黄色葡萄球菌。In some specific embodiments of the present invention, the microorganisms are bacteria, fungi and viruses, preferably, the bacteria are Escherichia coli and Staphylococcus aureus.
在本发明一个优选的实施例中，所述的半导体纳米阵列为氧化锌纳米棒阵列，且其表面修饰有金纳米颗粒。In a preferred embodiment of the present invention, the semiconductor nanoarray is a zinc oxide nanorod array, and the surface thereof is decorated with gold nanoparticles.
本发明另一个方面提供半导体涂层的制备方法，其包括如下步骤：Another aspect of the present invention provides a method for preparing a semiconductor coating, comprising the steps of:
1)在基底表面形成环氧基；1) form epoxy groups on the surface of the substrate;
2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列；2) generating semiconductor nanoarrays on epoxy groups by hydrothermal method or anodizing method;
3)在半导体纳米阵列表面上修饰金属纳米颗粒。3) Modification of metal nanoparticles on the surface of semiconductor nanoarrays.
在本发明一些具体实施例中，在基底表面形成环氧基的方法为将基底与硅烷偶联剂，优选为γ―(2,3-环氧丙氧)丙基三甲氧基硅烷进行反应，获得环氧基。通过环氧基可以使得半导体纳米阵列与基底接触更密切，从而加强了电子传递过程，有利于提高抗菌效果。In some specific embodiments of the present invention, the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent, preferably γ-(2,3-glycidoxy)propyltrimethoxysilane, to obtain epoxy groups. The epoxy group can make the semiconductor nano-array and the substrate contact more closely, thereby enhancing the electron transfer process, which is beneficial to improve the antibacterial effect.
在本发明一些具体实施例中，以水热法在环氧基上生成氧化锌半导体纳米阵列的方法为锌盐溶液和氢氧化钠的醇溶液在100-150℃下反应制备种子层；然后加入环六亚甲基四胺和六水合醋酸锌的混合水溶液中水热处理生成氧化锌半导体纳米阵列。In some specific embodiments of the present invention, the method for generating zinc oxide semiconductor nanoarrays on epoxy groups by hydrothermal method is to react zinc salt solution and sodium hydroxide alcohol solution at 100-150 ° C to prepare a seed layer; then add ZnO semiconductor nanoarrays were generated by hydrothermal treatment in a mixed aqueous solution of cyclohexamethylenetetramine and zinc acetate hexahydrate.
在本发明一些具体实施例中，半导体纳米阵列表面上金属纳米颗粒的修饰方法为以磁控溅射方法沉积金属纳米颗粒。In some specific embodiments of the present invention, the method for modifying the metal nanoparticles on the surface of the semiconductor nanoarray is to deposit the metal nanoparticles by magnetron sputtering.
本发明再一个方面提供所述半导体涂层的用途，所述半导体涂层提供基底抗微生物活性的同时能够检测基底表面微生物含量。Yet another aspect of the present invention provides the use of the semiconductor coating, which provides the antimicrobial activity of the substrate while being capable of detecting the microbial content on the surface of the substrate.
本发明再一个方面提供了一种植入物，所述植入物具有上述半导体涂层。Yet another aspect of the present invention provides an implant having the above-mentioned semiconductor coating.
本发明再一个方面提供了一种物体表面微生物的检测方法，其包括以下步骤：Another aspect of the present invention provides a method for detecting microorganisms on the surface of an object, comprising the following steps:
1)在物体表面生成上述半导体涂层；1) generating the above-mentioned semiconductor coating on the surface of the object;
2)将已知浓度的微生物液体涂覆在上述包含半导体涂层的物体表面，并检测该表面的电流，然后绘制电流与细菌浓度之间的曲线；2) Coat the surface of the above-mentioned object containing the semiconductor coating with a microorganism liquid of known concentration, and detect the current on the surface, and then draw a curve between the current and the bacterial concentration;
3)检测物体表面的电流，根据上述曲线计算物体表面细菌数量。3) Detect the current on the surface of the object, and calculate the number of bacteria on the surface of the object according to the above curve.
在本发明一些具体实施例中，所述的检测方法中，已知浓度的微生物液体为至少3个不同已知浓度的微生物液体，优选为3-6个不同已知浓度的微生物液体。In some specific embodiments of the present invention, in the detection method, the microbial liquid of known concentration is at least 3 microbial liquids of different known concentrations, preferably 3-6 microbial liquids of different known concentrations.
在本发明一些具体实施例中，所述的检测方法中，已知浓度的微生物液体的浓度为1-10 6CFU mL -1。 In some specific embodiments of the present invention, in the detection method, the concentration of the microbial liquid of known concentration is 1-10 6 CFU mL -1 .
在本发明一些具体实施例中，所述的检测方法中，检测物体表面的电流时，电流读取时间在5min以内。In some specific embodiments of the present invention, in the detection method, when the current on the surface of the object is detected, the current reading time is within 5 minutes.
在本发明一些具体实施例中，检测物体表面的电流的设备选自电化学工作站或微电流计。In some specific embodiments of the present invention, the device for detecting the current on the surface of the object is selected from an electrochemical workstation or a micro-galvanometer.
在本发明一些具体实施例中，检测物体表面的电流的设备为能够检测为100μA以下电流的设备。In some specific embodiments of the present invention, the device for detecting the current on the surface of the object is a device capable of detecting a current of less than 100 μA.
在本发明一些具体实施例中，检测物体表面的电流的设备中所使用的电解液选自肉汤培养基、生理盐水以及磷酸盐缓冲液(PBS)。In some specific embodiments of the present invention, the electrolyte used in the device for detecting the current on the surface of the object is selected from broth culture medium, physiological saline and phosphate buffered saline (PBS).
一种物体表面微生物浓度评估的建立方法，其包括以下步骤：A method for establishing microbial concentration assessment on an object surface, comprising the following steps:
1)在物体表面生成上述半导体涂层；1) generating the above-mentioned semiconductor coating on the surface of the object;
2)将已知浓度的微生物液体涂覆在上述包含半导体涂层的物体表面，并检测该表面的电流，然后绘制电流与细菌浓度之间的曲线；2) Coat the surface of the above-mentioned object containing the semiconductor coating with a microorganism liquid of known concentration, and detect the current on the surface, and then draw a curve between the current and the bacterial concentration;
3)检测物体表面的电流，根据上述曲线计算物体表面细菌数量；3) Detect the current on the surface of the object, and calculate the number of bacteria on the surface of the object according to the above curve;
其中所述的已知浓度的微生物液体为混合微生物液体，所述已知浓度的微生物液体为100种不同已知浓度的微生物液体。The microorganism liquid of known concentration is mixed microorganism liquid, and the microorganism liquid of known concentration is 100 kinds of microorganism liquid of known concentration.
优选地，所述已知浓度的微生物液体为1000种以上不同已知浓度的微生物液体。Preferably, the microorganism liquid of known concentration is more than 1000 kinds of microorganism liquid of different known concentration.
在本抗菌体系建立过程中，首先设计由半导体组成的涂层，然后将材料与细菌相互作用，接入电化学工作站或微电流计测试界面电流，通过电流大小可得知细菌数量，细菌电流同时在短时间内实现对细菌呼吸链电子传递的干扰而抑制其生长繁殖。During the establishment of this antibacterial system, a coating composed of semiconductors is first designed, and then the material is interacted with bacteria, and an electrochemical workstation or a microcurrent meter is connected to test the interface current. The number of bacteria can be known by the magnitude of the current. In a short time, it can interfere with the electron transfer of the bacterial respiratory chain and inhibit its growth and reproduction.
具体实施方案包括：Specific implementations include:
对植入体预处理并对表面进行半导体涂层设计Pretreatment of implants and design of semiconductor coatings on surfaces
植入体以钛合金为例，将钛合金加工成长宽高各为30mm、30mm、0.5mm的长方体并将其抛光打磨，然后依次在丙酮、乙醇、水中超声清洗10min，用氮气吹干备用。将以上钛合金材料浸泡于NaOH水溶液(10M)2h,与γ―(2,3-环氧丙氧)丙基三甲氧基硅烷KH-560(2％v/v)作用10h以形成环氧功能基团。然后准备Zn(CH 3COO) 2·2H 2O(10mM)和NaOH(30mM)的甲醇溶液，吸取10μL滴至样品表面并在120℃处理5min并重复三次以制备种子层。接下来将以上样品置于环六亚甲基四胺(50mM)和六水合醋酸锌(50mM)的混合水溶液中，于96℃水热处理1-24h以生成氧化锌纳米棒半导体。反应后将样品用5mL水冲洗2min并用氮气吹干。然后用磁控溅射方法向纳米棒沉积金纳米颗粒从而增强半导体的电子传输能力。 Taking titanium alloy as an example for the implant, the titanium alloy was processed into a rectangular parallelepiped with a length, width and height of 30mm, 30mm and 0.5mm, polished and ground, and then ultrasonically cleaned in acetone, ethanol and water for 10 minutes, and dried with nitrogen for use. Soak the above titanium alloy material in NaOH aqueous solution (10M) for 2h, and react with γ-(2,3-glycidoxy)propyltrimethoxysilane KH-560 (2%v/v) for 10h to form epoxy function group. Then prepare a methanol solution of Zn(CH 3 COO) 2 ·2H 2 O (10 mM) and NaOH (30 mM), pipette 10 μL drop onto the sample surface and treat at 120° C. for 5 min and repeat three times to prepare a seed layer. Next, the above samples were placed in a mixed aqueous solution of cyclohexamethylenetetramine (50 mM) and zinc acetate hexahydrate (50 mM), and hydrothermally treated at 96° C. for 1-24 h to generate zinc oxide nanorod semiconductors. After the reaction, the sample was rinsed with 5 mL of water for 2 min and blown dry with nitrogen. Gold nanoparticles were then deposited onto the nanorods by magnetron sputtering to enhance the electron transport capability of the semiconductor.
将材料与细菌进行作用并绘制细菌电流与细菌数量关系的标准关系式Standard relationships for interacting materials with bacteria and plotting bacterial current versus bacterial population
将上述载有纳米金修饰的氧化锌纳米棒的钛合金接入电化学工作站，并在材料表面加入菌液，菌液浓度为1-10 6CFU mL -1，记录细菌电流的大小同时绘制细菌电流与细菌数量的关系式。二者关系为电流(μA)＝-1.43+0.56*log CFU。 The above-mentioned titanium alloy loaded with nano-gold-modified zinc oxide nanorods was connected to the electrochemical workstation, and bacterial liquid was added on the surface of the material. The bacterial liquid concentration was 1-10 6 CFU mL -1 , and the bacterial current was recorded and the bacteria were drawn. The relationship between the current and the number of bacteria. The relationship between the two is current (μA)=-1.43+0.56*log CFU.
将材料与细菌进行作用检测杀菌结果Interaction of materials with bacteria to detect sterilization results
向上述材料表面滴入菌液，菌液浓度为1-10 6CFU mL -1，将材料与细菌相互作用一定时间(1-180min)，对细菌进行涂板及生理活性检测以验证抗菌效果。 Bacterial liquid was dropped onto the surface of the above materials, the concentration of the bacterial liquid was 1-10 6 CFU mL -1 , the material was interacted with the bacteria for a certain time (1-180 min), and the bacteria were coated and tested for physiological activity to verify the antibacterial effect.
实施例1Example 1
将钛合金加工成长宽高各为30mm、30mm、0.5mm的长方体并将其抛光打磨，然后依次在丙酮、乙醇、水中超声清洗10min，用氮气吹干备用。将以上钛合金材料浸泡于NaOH水溶液(10M)2h,与KH-560(2％v/v)作用10h以形成环氧功能基团。然后准备Zn(CH 3COO) 2·2H 2O(10mM)和NaOH(30mM)的甲醇溶液，吸取10μL滴至样品表面并在120℃处理5min并重复三次以制备种子层。接下来将以上样品置于环六亚甲基四胺(50mM)和六水合醋酸锌(50mM)的混合水溶液中，于96℃水热处理10-12h以生成ZnO纳米棒半导体。反应后将样品用5mL水冲洗2min并用氮气吹干。然后用磁控溅射方法向纳米棒沉积金纳米颗粒从而增强半导体的电子传输能力。通过扫描电子显微镜对样品表面微观形 态进行观察，得到如图1a所示微观形貌。由图可见，氧化锌纳米棒的直径为100nm，纳米金颗粒贴附在纳米棒上或者填充在纳米棒之间(如图1箭头所示)。 The titanium alloy was processed into a rectangular parallelepiped with a length, width and height of 30mm, 30mm, and 0.5mm, polished and ground, and then ultrasonically cleaned in acetone, ethanol, and water for 10 minutes, and dried with nitrogen for use. The above titanium alloy materials were soaked in NaOH aqueous solution (10M) for 2h, and reacted with KH-560 (2%v/v) for 10h to form epoxy functional groups. Then prepare a methanol solution of Zn(CH 3 COO) 2 ·2H 2 O (10 mM) and NaOH (30 mM), pipette 10 μL drop onto the sample surface and treat at 120° C. for 5 min and repeat three times to prepare a seed layer. Next, the above samples were placed in a mixed aqueous solution of cyclohexamethylenetetramine (50 mM) and zinc acetate hexahydrate (50 mM), and hydrothermally treated at 96 °C for 10-12 h to generate ZnO nanorod semiconductors. After the reaction, the sample was rinsed with 5 mL of water for 2 min and blown dry with nitrogen. Gold nanoparticles were then deposited onto the nanorods by magnetron sputtering to enhance the electron transport capability of the semiconductor. The microscopic morphology of the sample surface was observed by scanning electron microscope, and the microscopic morphology shown in Fig. 1a was obtained. It can be seen from the figure that the diameter of the zinc oxide nanorods is 100 nm, and the gold nanoparticles are attached to the nanorods or filled between the nanorods (as shown by the arrows in Figure 1).
实施例2Example 2
对实施例1中处理得到的样品表面进行元素含量分析。能谱图谱(图1b)显示锌、氧、金、钛元素均匀分布与样品表面，表明氧化锌涂层及金纳米颗粒均匀分布。Elemental content analysis was performed on the surface of the sample treated in Example 1. The energy spectrum (Fig. 1b) shows that zinc, oxygen, gold, and titanium elements are uniformly distributed on the surface of the sample, indicating that the zinc oxide coating and the gold nanoparticles are uniformly distributed.
实施例3Example 3
将实施例1中所得样品与不同浓度大肠杆菌(浓度为1、10 3、10 5和10 6CFU mL -1)作用，制作细菌数量与细菌电流的散点图，进行拟合。结果如图2所示。细菌数量的对数值与细菌电流成线性关系，相关系数高达0.98。说明采用检测得到的电流与细菌含量有线性关系，可以通过电流检测预测细菌含量。 The samples obtained in Example 1 were reacted with different concentrations of Escherichia coli (concentrations of 1, 10 3 , 10 5 and 10 6 CFU mL -1 ) to make a scatter plot of bacterial number and bacterial current, and fit. The results are shown in Figure 2. The logarithmic number of bacteria was linearly related to bacterial current with a correlation coefficient as high as 0.98. It shows that the current obtained by the detection has a linear relationship with the bacterial content, and the bacterial content can be predicted by the current detection.
实施例4Example 4
向实施例1中样品表面平铺100μL大肠杆菌(细菌数量设为N 0)，使样品与大肠杆菌作用，作用时间1h，吸取10μL菌液至固体培养基，用涂板计数方法检测细菌数量(N 1)，抗菌效率 Spread 100 μL of Escherichia coli (the number of bacteria is set as N 0 ) on the surface of the sample in Example 1, make the sample act with Escherichia coli, the action time is 1h, draw 10 μL of bacterial liquid to the solid medium, and use the plate counting method to detect the number of bacteria ( N 1 ), antibacterial efficiency
R＝(10N 1-N 0/N 1)*100％ R=(10N 1 -N 0 /N 1 )*100%
结果如图3a,3b所示。在作用1h内，细菌电流越来越小，杀菌率越来越高，1h作用可达到80％的抗菌效果。证明本发明的半导体涂层具有良好的抗菌效果，能够在短时间内实现高效的抗菌。同时证实了本发明的产品是通过电流获得的抗菌效果。The results are shown in Figure 3a, 3b. Within 1h of action, the bacterial current is getting smaller and smaller, and the sterilization rate is getting higher and higher, and the action of 1h can reach 80% of the antibacterial effect. It is proved that the semiconductor coating of the present invention has a good antibacterial effect and can achieve efficient antibacterial in a short time. At the same time, it is confirmed that the antibacterial effect of the product of the present invention is obtained by electric current.
实施例5Example 5
将实施例1中所得样品与不同浓度大肠杆菌与金黄色葡萄球菌混合菌液(浓度为1、10 3、10 5和10 6CFU mL -1)作用，制作细菌数量与细菌电流的散点图，进行拟合。结果如图4所示。混合细菌数量的对数值与细菌电流成线性关系，相关系数高达0.96。说明采用检测得到的电流与混合细菌含量有线性关系，可以通过电流检测预测多种菌种混合菌液中细菌数量。 The sample obtained in Example 1 was acted on with different concentrations of Escherichia coli and Staphylococcus aureus mixed bacterial solution (concentrations were 1, 10 3 , 10 5 and 10 6 CFU mL -1 ) to make a scatter plot of bacterial number and bacterial current , to fit. The results are shown in Figure 4. The logarithm of the mixed bacterial count was linearly related to the bacterial current with a correlation coefficient as high as 0.96. It shows that the current obtained by the detection has a linear relationship with the mixed bacterial content, and the number of bacteria in the mixed bacterial solution of various bacterial species can be predicted by current detection.

Claims (11)

  1. 一种抗微生物且能自测微生物数量的半导体涂层，所述半导体涂层在基底上的生成的环氧基上原位生成的半导体纳米阵列，所述半导体纳米阵列选自氧化锌纳米材料阵列、二氧化钛纳米材料阵列、硅阵列；半导体纳米阵列表面还包括金属纳米颗粒的修饰。A kind of semiconductor coating which is antimicrobial and can measure the number of microorganisms, the semiconductor nano-array is generated in situ on the generated epoxy group on the substrate, and the semiconductor nano-array is selected from the zinc oxide nano-material array , TiO2 nanomaterial arrays, silicon arrays; the surface of semiconductor nanoarrays also includes the modification of metal nanoparticles.
  2. 根据权利要求1所述的的半导体涂层，所述半导体涂层在基底上生成的环氧基上原位生成的半导体纳米阵列的方法为：1)在基底表面形成环氧基；2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列。The semiconductor coating according to claim 1, wherein the method for in-situ generation of semiconductor nanoarrays on epoxy groups generated by the semiconductor coating on the substrate is: 1) forming epoxy groups on the surface of the substrate; 2) using Hydrothermal or anodizing methods generate semiconductor nanoarrays on epoxy groups.
  3. 根据权利要求2所述的的半导体涂层，在基底表面形成环氧基的方法为将基底与硅烷偶联剂进行反应，获得环氧基，优选地，硅烷偶联剂为γ-(2,3-环氧丙氧)丙基三甲氧基硅烷。The semiconductor coating according to claim 2, the method for forming an epoxy group on the surface of the substrate is to react the substrate with a silane coupling agent to obtain an epoxy group, preferably, the silane coupling agent is γ-(2, 3-glycidoxy)propyltrimethoxysilane.
  4. 一种物体表面微生物的检测方法，其包括以下步骤：A method for detecting microorganisms on the surface of an object, comprising the following steps:
    1)在物体表面生成权利要求1-3任一项所述的半导体涂层；1) generating the semiconductor coating according to any one of claims 1-3 on the surface of an object;
    2)将已知浓度的微生物液体涂覆在包含所述半导体涂层的物体表面，并检测该表面的电流，然后绘制电流与微生物浓度之间的曲线；2) Coat the surface of the object containing the semiconductor coating with a microorganism liquid of known concentration, and detect the current on the surface, and then draw a curve between the current and the concentration of microorganisms;
    3)检测物体表面的电流，根据所述曲线计算物体表面微生物数量；3) detect the current on the surface of the object, and calculate the number of microorganisms on the surface of the object according to the curve;
    优选地，所述的检测方法中，已知浓度的微生物液体为至少3个不同已知浓度的微生物液体。Preferably, in the detection method, the microbial liquids of known concentration are at least three microbial liquids of different known concentrations.
  5. 根据权利要求4所述的检测方法，所述的检测方法中，检测物体表面的电流时，电流读取时间在5min以内；The detection method according to claim 4, wherein in the detection method, when detecting the current on the surface of the object, the current reading time is within 5 minutes;
    优选地，检测物体表面的电流的设备为能够检测为100μA以下电流的设备。Preferably, the device for detecting the current on the surface of the object is a device capable of detecting a current of less than 100 μA.
  6. 根据权利要求1-3任一项所述的半导体涂层的用途，所述半导体涂层提供基底抗微生物活性的同时能够用于检测基底表面微生物含量。The use of a semiconductor coating according to any one of claims 1-3, which can be used to detect the microbial content of a substrate surface while providing the substrate antimicrobial activity.
  7. 根据权利要求1-3任一项所述的半导体涂层的制备方法，其包括如下步骤：The preparation method of the semiconductor coating according to any one of claims 1-3, it comprises the steps:
    1)在基底表面形成环氧基；1) form epoxy groups on the surface of the substrate;
    2)以水热法或者阳极氧化法在环氧基上生成半导体纳米阵列；2) generating semiconductor nanoarrays on epoxy groups by hydrothermal method or anodizing method;
    3)在半导体纳米阵列表面上修饰金属纳米颗粒；3) Modifying metal nanoparticles on the surface of semiconductor nanoarrays;
    优选地，以水热法在环氧基上生成氧化锌半导体纳米阵列的方法为锌盐溶液和氢氧化钠 的醇溶液在100-150℃下反应制备种子层；然后加入环六亚甲基四胺和六水合醋酸锌的混合水溶液中水热处理生成氧化锌半导体纳米阵列；Preferably, the method for generating zinc oxide semiconductor nanoarrays on epoxy groups by a hydrothermal method is to react a zinc salt solution and an alcohol solution of sodium hydroxide at 100-150° C. to prepare a seed layer; then add cyclohexamethylenetetrakis Hydrothermal treatment in a mixed aqueous solution of amine and zinc acetate hexahydrate to generate zinc oxide semiconductor nanoarrays;
    优选地，半导体纳米阵列表面上金属纳米颗粒的修饰方法为以磁控溅射方法沉积金属纳米颗粒。Preferably, the method for modifying the metal nanoparticles on the surface of the semiconductor nanoarray is to deposit the metal nanoparticles by a magnetron sputtering method.
  8. 根据权利要求7所述的制备方法，在基底表面形成环氧基的方法为将基底与硅烷偶联剂进行反应，在基底表面获得环氧基，优选地，硅烷偶联剂为γ―(2,3-环氧丙氧)丙基三甲氧基硅烷。According to the preparation method of claim 7, the method for forming epoxy groups on the surface of the substrate is to react the substrate with a silane coupling agent to obtain epoxy groups on the surface of the substrate, preferably, the silane coupling agent is γ-(2 , 3-glycidoxy) propyl trimethoxy silane.
  9. 一种植入物，所述植入物表面具有权利要求1-3任一项所述的半导体涂层。An implant having the semiconductor coating of any one of claims 1-3 on the surface of the implant.
  10. 一种物体表面微生物控制和检测***，其包括电流检测设备、至少3个已知浓度的微生物液体以及在物体表面形成权利要求1-3任一项所述的半导体涂层的材料；An object surface microorganism control and detection system, comprising current detection equipment, at least 3 microbial liquids of known concentration and a material for forming the semiconductor coating of any one of claims 1-3 on the object surface;
    优选地，检测物体表面的电流的设备为能够检测为100μA以下电流的设备；Preferably, the device for detecting the current on the surface of the object is a device capable of detecting a current below 100 μA;
    优选地，在物体表面形成权利要求1-3任一项所述的半导体涂层的材料包括硅烷偶联剂、锌盐溶液、氢氧化钠、环六亚甲基四胺、六水合醋酸锌和金属纳米颗粒。Preferably, the material for forming the semiconductor coating according to any one of claims 1-3 on the surface of the object comprises silane coupling agent, zinc salt solution, sodium hydroxide, cyclohexamethylenetetramine, zinc acetate hexahydrate and metal nanoparticles.
  11. 一种物体表面微生物浓度评估的建立方法，其包括以下步骤：A method for establishing microbial concentration assessment on an object surface, comprising the following steps:
    1)在物体表面生成权利要求1-3任一项所述的半导体涂层的材料；1) a material for generating the semiconductor coating according to any one of claims 1-3 on the surface of an object;
    2)将已知浓度的微生物液体涂覆在上述包含半导体涂层的物体表面，并检测该表面的电流，然后绘制电流与细菌浓度之间的曲线；2) Coating the microorganism liquid of known concentration on the surface of the above-mentioned object comprising the semiconductor coating, and detecting the current on the surface, and then drawing a curve between the current and the bacterial concentration;
    3)检测物体表面的电流，根据上述曲线计算物体表面细菌数量；3) Detect the current on the surface of the object, and calculate the number of bacteria on the surface of the object according to the above curve;
    其中所述的已知浓度的微生物液体为混合微生物液体，所述已知浓度的微生物液体为100种不同已知浓度的微生物液体；The microbial liquid of known concentration is a mixed microbial liquid, and the microbial liquid of known concentration is 100 kinds of microbial liquids of different known concentrations;
    优选地，所述已知浓度的微生物液体为1000种以上不同已知浓度的微生物液体；更优选为10000种以上不同已知浓度的微生物液体。Preferably, the microorganism liquid of known concentration is more than 1000 kinds of microorganism liquid of different known concentration; more preferably, it is more than 10,000 kinds of microorganism liquid of different known concentration.
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