Application of self-powered sensor in monitoring and early warning of bacterial infection of implanted equipment
By using self-energized sensors in the implanted equipment, using the open-circuit voltage signals formed by glucose and bacterial biofilms in the organism to monitor and early warning bacterial infections in the implanted equipment in real time, the problem of difficulty in effective monitoring and early warning in the prior art is solved, and the equipment usage cycle is extended and high sensitivity detection is achieved.
Patent Information
- Application Number
- CN202510158246.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-13
- Publication Date
- 2025-06-24
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The prior art is difficult to effectively monitor and early warning of bacterial infections in the biological body of implanted equipment, resulting in a shortening of the equipment's usage cycle and an increase in the treatment cost.
Self-energy sensors are used, including anode with glucose-like oxidase activity and a cathode with laccase-like activity. Using glucose in the organism as fuel, different open-circuit voltage signals formed by the bacterial biofilm on the electrode surface can monitor and early warning of bacterial infections in implanted equipment in real time.
It realizes real-time monitoring and early warning of bacterial infections in implanted equipment, extends the use cycle of the equipment, maintains high sensitivity and specificity, and is non-toxic and contaminated.
Smart Images
Figure CN120193047A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of self-powered sensors, and particularly relates to the application of a self-powered sensor in the monitoring and early warning of bacterial infections in implanted devices. Background Art
[0002] Implantable biological devices represent the rapid development direction of personalized medicine and have extensive applications in biotechnology and life sciences. For example, the detection of neurotransmitters in the brain has attracted wide attention due to its important role in nerve activities. These miniaturized devices can amplify the biorecognition of analytes into detectable electrical signals. Compared with traditional diagnostics, biocompatible implantable devices have the advantages of simple preparation and low cost. However, currently, most implantable biological devices have poor biocompatibility, and the long-term application of the biomaterials of implanted devices will cause bacteria and other microorganisms to adhere and infect on their surfaces. Once an infection occurs, it will not only increase the hospitalization costs of patients, but also face problems such as the need to remove the implant and perform re-surgery. Therefore, how to effectively monitor and early warn the bacterial infection situation of implanted devices, understand the bacterial infection situation of implanted devices in the body at any time, make timely treatment or maintenance, replacement, extend their service life, and maintain the high sensitivity and specificity of implanted devices has important clinical practical significance. Summary of the Invention
[0003] In order to solve the problems such as the inability to effectively monitor and early warn the bacterial infection situation of implantable biological devices in vivo, the present invention provides an application of a self-powered sensor in the monitoring and early warning of bacterial infections in implanted devices.
[0004] In order to solve the above technical problems, the present invention adopts the following technical solutions:
[0005] An application of a self-powered sensor in the monitoring and early warning of bacterial infections in implanted devices, including an anode with glucose oxidase-like activity and a cathode with laccase-like activity. The sensor is implanted into a living body along with the implanted device and uses glucose in the living body as fuel. A bacterial biofilm is formed on the surface of the electrode in the living body infected with bacteria, thereby obtaining different open-circuit voltage signals. The real-time monitoring and early warning of the bacterial infection situation of the implanted device in the living body are realized through the change of the open-circuit voltage signal.
[0006] The connection method of the sensor and the implanted device is to attach the anode and the cathode to both sides of the implanted device model respectively, and the two electrodes are connected by wires.
[0007] Further, the specific method for the sensor to monitor and early warn the bacterial infection situation of the implanted device is as follows:
[0008] The sensor is implanted into a living organism together with the implantable device, and the open-circuit voltage of the sensor in the living organism is detected.
[0009] In a normal living organism, the anode catalyzes the oxidation of glucose in the living organism to generate electrons that reach the cathode. The cathode receives the electrons and catalyzes the reduction of oxygen to water, forming a circuit. The sensor not infected by bacteria can work normally and output a normal open-circuit voltage.
[0010] In a living organism infected with bacteria, the electrode surface of the sensor will be synchronously and frequency-synchronously infected by bacteria together with the implant device, forming a biofilm. The active sites of the electrode are covered, the potential difference decreases, and different open-circuit voltage signals are obtained, thereby realizing in-situ real-time monitoring and early warning of the bacterial infection situation of the implant device, and the implant device can be subsequently processed according to the bacterial infection situation.
[0011] Furthermore, the implant device model can be selected as a medical silicone catheter; the diameter of the catheter is 2 - 5 mm, and the length is 5 - 10 mm.
[0012] Furthermore, the width of the anode and the cathode is 1 - 2 mm, and the length is 5 - 10 mm.
[0013] Furthermore, the anode is a nanozyme electrode Co / Fe-LIG, and the cathode is a nanozyme electrode Cu-LIG.
[0014] A biofuel cell is a green energy technology that converts chemical energy into electrical energy using bio-catalyzed redox reactions. Its structure and installation are simple (only two electrodes and a voltmeter are needed), it has excellent biocompatibility, and it can directly use organic substances such as glucose in a living organism as fuel and operate without an external power source. However, so far, there has been no report on the research of a self-powered sensor based on a biofuel cell for real-time monitoring of bacterial infections of implantable devices.
[0015] The present invention provides an application of a self-powered sensor in the monitoring and early warning of bacterial infections of implant devices. The sensor is implanted into a living organism together with the implant device, and the real-time monitoring and early warning of the bacterial infection situation of the implant device are realized through the change of the open-circuit voltage signal of the sensor. The present invention first applies a biofuel cell sensor to the real-time monitoring and early warning of bacterial infections of implant devices. This biosensor has good biocompatibility, can directly use organic substances such as glucose in a living organism as fuel, operates self-powered normally in a living organism, and is non-toxic and pollution-free, and will not cause obvious harm to the living organism after implantation.
[0016] Secondly, the biofuel cell sensor has a simple structure and installation. It only needs two electrodes and wires to operate on the implantable model, and the detection method is simple. The open-circuit voltage can be measured through an electrochemical workstation.
[0017] Finally, the self-powered sensor provided by the present invention can realize in-situ real-time monitoring and early warning of the bacterial infection situation of the implanted device, and can always understand the bacterial contamination situation of the implanted biological device in the body, and corresponding treatment and replacement can be made in time, so as to extend the service life of the implanted device; moreover, the output signal of the sensor provided by the present invention changes significantly, and it can maintain high sensitivity and specificity, and the stability is also better. This is of great significance for the development of implanted devices and medical detection. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 It is a schematic diagram of the activity of anode-like glucose oxidase provided in Embodiment 1 of the present invention;
[0019] Figure 2 It is a schematic diagram of the activity of cathode-like laccase provided in Embodiment 2 of the present invention;
[0020] Figure 3 It is a schematic diagram of the detection principle of the self-powered sensor provided in Embodiment 3 of the present invention;
[0021] Figure 4 It is a physical diagram of the self-powered sensor provided in Embodiment 3 of the present invention;
[0022] Figure 5 It is a schematic diagram of the output signal of the self-powered sensor for detecting in vitro simulated bacterial infection provided in Embodiment 4 of the present invention;
[0023] Figure 6 It is a schematic diagram of the output signal of the self-powered sensor for detecting bacterial infection in mice provided in Embodiment 5 of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0024] The present invention discloses an application of a self-powered sensor in the monitoring and early warning of bacterial infection of implanted devices. Those skilled in the art can draw on the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all regarded as included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and those skilled in the art can obviously make changes or appropriate modifications and combinations to the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.
[0025] In order to enable those skilled in the art to better understand the present invention, the present invention will be further described in detail below in conjunction with specific embodiments.
[0026] Embodiment 1 Detection of the Activity of Anode Electrodes-like Glucose Oxidase
[0027] The activity of glucose oxidase-like enzyme of the present invention can be determined by the colorimetric detection of H2O2. The anode electrode Co / Fe-LIG and glucose (50 mmol / L) were added to a 1 mL test tube containing 10 mmol / L HEPES pH 7.4 to form a 900 μL mixed solution. After reacting at 37 °C for 30 min, 500 μL of the above solution was taken and added to a solution containing 380 μL of NaAc-HAc buffer solution (30 mmol / L, pH 4.0). 20 μL of horseradish peroxidase HRP (0.1 mg mL -1 ) and 100 μL of 3,3',5,5'-tetramethylbenzidine TMB (5 mmol / L) were added to the solution. After reacting at 37 °C for 15 min, the color change of the characteristic absorption peak at 652 nm was observed by ultraviolet-visible absorption spectroscopy. Figure 1 Figure for the activity of anode glucose oxidase-like enzyme, Figure 1 showing that the selected anode has glucose oxidase-like enzyme activity and can oxidize glucose to lose electrons, ensuring the feasibility of sensor construction.
[0028] Example 2 Detection of laccase-like enzyme activity of cathode electrode
[0029] The catalytic performance of the present invention was determined by the color reaction of 2,4-dichlorophenol 2,4-DP and 4-aminoantipyrine 4-AP. First, the solutions of 4-AP (1 mg / mL, 100 μL) and 2,4-DP (1 mg / mL, 100 μL) were mixed with MES buffer solution (30 mmol / L, pH 6.8, 800 μL), and then the cathode electrode Cu-LIG was added. After reacting at 37 °C for 15 min, the absorbance of the supernatant at 510 nm was measured. Figure 2 Figure for the activity of cathode laccase-like enzyme, Figure 2 showing that the selected cathode has laccase-like enzyme activity and can reduce oxygen to water to obtain electrons, also ensuring the feasibility of sensor construction.
[0030] The present invention has no particular limitation on the anode electrode and the cathode electrode, but the anode electrode needs to have glucose oxidase-like enzyme activity, and the cathode electrode needs to have laccase-like enzyme activity. For the specific test results to be presented, in Example 1 of the present invention, the nanozyme electrode Co / Fe-LIG is specifically preferred as the anode electrode, and in Example 2, the nanozyme electrode Cu-LIG is specifically preferred as the cathode electrode.
[0031] The preparation method of the nanozyme electrode of the present invention can preferably be prepared according to the following method:
[0032] FeCl3·6H2O and Co(NO3)2·6H2O were dissolved in ultrapure water to form an anode precursor solution; Cu(NO3)2·6H2O was dissolved in ultrapure water to form a cathode precursor solution;
[0033] A polyimide (PI) film was selected as the substrate, and a laser-induced graphene (LIG) electrode was prepared by using laser scanning technology. The laser power and scanning rate could be set at 3.2 W and 40 mm / s, respectively. The above-mentioned anode and cathode precursor solutions were uniformly dropped into the above LIG electrode, and then the solvent was dried and evaporated at room temperature in air. The modified LIG electrode was scanned twice at the same scanning rate to produce nanozyme electrodes Co / Fe-LIG and Cu-LIG.
[0034] Preparation and Detection Principle of Self-Powered Sensor in Example 3
[0035] According to the actual situation, appropriate types of anode electrodes with glucose oxidase-like activity and cathode electrodes with laccase-like activity were selected. In this example, the nanozyme electrode Co / Fe-LIG was specifically preferred as the anode electrode, and the nanozyme electrode Cu-LIG was specifically preferred as the cathode electrode. The width of the electrode was 1-2 mm, and the length was 5-10 mm. The two electrodes were respectively attached to both sides of the implant device model. In this example, a medical silicone rubber catheter was specifically preferred, with a diameter of 2-5 mm and a length of 5-10 mm. One end of the electrode was connected to a wire with silver glue, and the two electrodes were connected by wires. The self-powered sensor was completed with the connection to the implant device model.
[0036] Figure 3 It is a schematic diagram of the detection principle of the self-powered sensor, as Figure 3 shown. Glucose is anodically oxidized to gluconic acid, and at the same time, electrons are lost and transmitted to the cathode through the external circuit. The cathode receives the electrons and reduces oxygen to water, forming a circuit. Based on the potential difference between the anode and cathode, the open-circuit voltage can be measured by an electrochemical workstation. If the sensor is infected by bacteria and a biofilm is formed on the electrode surface, the active sites of the nanozymes at the anode and cathode will be covered, the potential difference will decrease, and the open-circuit voltage will also decrease accordingly. The sensor is attached to both sides of the implant device and can be synchronously and co-frequency infected by bacteria in the living body. Therefore, the bacterial infection situation of the implant device can be directly monitored in real time and in situ through the open-circuit voltage signal of the sensor. Figure 4 It is a physical picture of the self-powered sensor with a medical catheter as the model.
[0037] Detection of In Vitro Simulated Bacterial Infection of Self-Powered Sensor in Example 4
[0038] The self-powered sensor obtained by the same method as in Example 3 was placed in a 12-well microtiter plate, and 1.5 mL of Staphylococcus aureus suspension (OD600 = 0.1) was added to the wells. It was cultured at 37 °C for 24 hours. Finally, the sensor was rinsed with PBS to remove the LB medium, and a Staphylococcus aureus biofilm was obtained on the surface of the sensor electrode. The sensors without and with biofilm coverage were respectively placed in 5 - 10 mL of 0.9% saline solution containing 50 mol / L glucose, and the open-circuit voltage was measured by an electrochemical workstation to obtain different open-circuit signals. The open-circuit signal data are shown in Figure 5 .
[0039] Figure 5 It shows that the sensor not infected with bacteria outputs a normal open-circuit voltage, while the sensor infected with bacteria outputs an open-circuit voltage close to zero.
[0040] Example 5 Monitoring and warning of bacterial infection in implanted devices by self-powered sensors
[0041] The connection of the self-powered sensor to the implanted device model was completed by the same method as in Example 3. Then, the implanted device models connected with the self-powered sensors were respectively implanted into non-infected and infected mice, and the open-circuit voltage signals of the sensors in the two groups of mice were monitored at any time: There are two methods for constructing the infection model of the infected mice. One is that after the implant is implanted subcutaneously in the mouse, bacterial infection is achieved by subcutaneous injection; the other is that the implant is carried with bacteria or biofilm in vitro and then implanted subcutaneously in the mouse. In this example, the second method for constructing the infection model is taken as an example. The implanted device model connected with the self-powered sensor was placed in the bacterial solution in vitro for 0 - 36 h, and then implanted into the mouse for 0 - 7 days of culture; at the same time, the implanted device model connected with the self-powered sensor that was not cultured with bacteria in vitro was implanted into the mouse for 0 - 7 days of culture as a control group. The open-circuit voltage of the sensor in the mice of different experimental groups was measured. The open-circuit signal data are shown in Figure 6 .
[0042] Figure 6It is shown that sensors in mice without bacterial infection (0 h of in vitro bacterial culture, 0.5 days of in vivo growth) and with bacterial infection (24 h of in vitro bacterial culture, 0.5 days of in vivo growth) produce different open-circuit signals, and the signal data is generally similar to the open-circuit signal data obtained by in vitro simulation; the surface of the sensor electrode in the case of bacterial infection carries Staphylococcus aureus or forms biofilms at different growth stages, and the active sites of the electrode are covered, resulting in a decrease in the potential difference, and the obtained open-circuit voltage signal shows a weakening. Since the surface of the sensor electrode and the implanted device model are synchronously and co-frequency infected by bacteria, the bacterial infection situation of the implanted device can be directly monitored and warned in real time through the change of the open-circuit signal of the sensor. The data shows that the change of the output signal of the sensor is obvious, and it can maintain high sensitivity and specificity, and the stability is also good.
[0043] In practical applications, if it is found that the bacterial infection of the implanted device reaches a certain level, antibiotic treatment or other treatment methods can be used in combination to extend the service life of the implanted device, or the implanted device can be repaired or replaced in a timely manner.
[0044] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art in the technical field, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.
Claims
1. Application of a self-powered sensor in monitoring and early warning of bacterial infection in implanted devices, the sensor comprising an anode having glucose oxidase-like activity and a cathode having laccase-like activity, characterized in that: The sensor is implanted into a living body along with an implant device, and uses glucose in the living body as fuel to infect bacteria on the electrode surface in the living body to form a bacterial biofilm, thereby obtaining different open-circuit voltage signals. The change in the open-circuit voltage signal realizes real-time monitoring and early warning of the bacterial infection of the implant device in the living body.
2. The use according to claim 1, characterized in that: The sensor is connected to the implant device in the following manner: the anode and cathode are respectively attached to two sides of the implant device model, and the two electrodes are connected by a wire.
3. The use according to claim 1, characterized in that: The specific method of using the sensor to monitor and warn of bacterial infection of implanted devices is: Implanting the sensor together with the implantation device into a living body, and detecting the open circuit voltage of the sensor in the living body; In a normal organism, the anode catalyzes the oxidation of glucose in the organism, generates electrons that reach the cathode, and the cathode obtains the electrons and catalyzes the reduction of oxygen into water, forming a circuit. The sensor that is not infected by bacteria works normally and can output a normal open circuit voltage. In a biological body infected with bacteria, the electrode surface of the sensor will be infected by bacteria at the same frequency and in sync with the implanted device, forming a bacterial biofilm. The active sites of the electrode are covered, the potential difference is reduced, and different open-circuit voltage signals are obtained, thereby realizing in-situ real-time monitoring and early warning of the bacterial infection of the implanted device, and subsequent treatment of the implanted device can be performed according to the bacterial infection situation.
4. The use according to claim 2, characterized in that: The implant device model is a medical silicone catheter; the catheter has a diameter of 2-5 mm and a length of 5-10 mm.
5. The use according to claim 1 or 4, characterized in that: The anode and cathode have a width of 1-2 mm and a length of 5-10 mm.
6. The use according to claim 1, characterized in that: The anode is a nanozyme electrode Co / Fe-LIG, and the cathode is a nanozyme electrode Cu-LIG.