Low energy surface acoustic wave based medical device biofilm prevention system

Abstract

The application discloses a medical instrument biofilm prevention system based on low-energy surface acoustic waves and relates to the technical field of medical instrument protection. The technical scheme is as follows: a piezoelectric vibration module is attached to or integrated with the wall part of an indwelling medical instrument, vibration is uniformly transmitted to the whole surface of the instrument, a vibration transmission module for exciting composite surface acoustic waves is arranged, a drive control module for outputting rectangular electric pulses and adjusting the power density of the instrument surface to be accurately maintained is arranged, and a power module is arranged. The application can reduce the biofilm load to 0.75-1.22 log 10 CFU / cm 2 At the same time, the urine sterility time is prolonged from 2 days to 9 days, and the infection time is delayed to the 7.3th day. The physical method adopted in the application is reversible, non-toxic and non-drug-inducing, is effective on a wide range of bacteria and fungi, does not cause tissue damage, and is suitable for catheters, central venous catheters and various indwelling instruments.

Description

Technical Field

[0001] This invention relates to the field of medical device protection technology, and more specifically, to a medical device biofilm prevention system based on low-energy surface acoustic waves. Background Technology

[0002] Indwelling medical devices (such as urinary catheters, central venous catheters, endotracheal tubes, and peritoneal dialysis catheters) are widely used in clinical practice, but their surfaces are highly susceptible to the formation of microbial biofilms. Biofilms are structured colonies formed by planktonic microorganisms that initially attach to the device surface, proliferate, secrete extracellular polysaccharide matrix, and differentiate. Once a biofilm forms, the resistance of microorganisms to antibiotics, disinfectants, and the host's immune defenses can increase by more than 1000 times, leading to persistent and recurrent device-related infections. Statistics show that the daily risk of bacteriuria in patients with indwelling urinary catheters is approximately 5% to 10%, and almost all patients with long-term indwelling catheters (≥28 days) develop infections, imposing a severe disease burden on patients and significantly increasing medical costs.

[0003] Currently, the mainstream technical solutions for biofilm prevention in indwelling medical devices can be divided into two main categories: chemical methods and physical methods.

[0004] Chemical methods primarily involve coating the instrument surface with antibacterial coatings (such as silver salts, hydrogels, antibiotics, etc.). These coatings inhibit microbial adhesion or kill contacting microorganisms by releasing antibacterial active substances. Some products have been used clinically, but their effectiveness is limited and has failed to significantly reduce the incidence of infection. At the same time, chemical coatings have inherent defects: first, the antibacterial components in the coating are depleted over time, resulting in poor durability and inability to remain effective throughout the entire indwelling period of the instrument; second, long-term, low-dose exposure to antibacterial substances can easily induce bacterial resistance, further exacerbating the difficulty of subsequent treatment; and third, some chemical coating materials may cause local tissue irritation or allergic reactions.

[0005] In physical approaches, ultrasound technology has been studied for its use in combating biofilms. However, existing ultrasound protocols primarily focus on the "treatment" of already formed biofilms, i.e., using high-power ultrasound to enhance the penetration of antibiotics into microorganisms within the biofilm ("ultrasound-assisted antibiotic therapy"), rather than actively blocking the initial formation of biofilms. These methods usually need to be used in combination with antibiotics and cannot be used as an independent physical preventative measure. Furthermore, the high power may lead to cavitation effects, causing thermal or mechanical damage to surrounding tissues, and under certain conditions, may even activate bacterial adhesion mechanisms, thereby promoting biofilm formation.

[0006] In summary, existing technologies still have the following problems in preventing biofilm formation in indwelling medical devices:

[0007] (1) Chemical coatings rely on antibacterial substances: they are prone to bacterial resistance and have poor coating durability, making it impossible to achieve long-term and stable antibacterial effects;

[0008] (2) Existing ultrasound technology is not properly positioned: it is mainly used to enhance the penetration of antibiotics into mature biofilms rather than to block the initial attachment of microorganisms, and it usually needs to be used in combination with drugs, which increases the complexity of treatment and the risk of side effects;

[0009] (3) Lack of safe and independent physical prevention methods: There is no physical prevention system that does not require chemical additives, is reversible, low-energy, applicable to a variety of instrument surfaces, and can directly interfere with the initial adhesion steps of microorganisms;

[0010] (4) Lack of energy threshold control: Existing mechanical vibration technology does not accurately control energy density in layers, ignoring the phenomenon that low energy and high energy have diametrically opposite effects on microbial adhesion (i.e., high energy may activate the force-induced adhesion enhancement effect), which poses a potential risk of "the more you prevent, the stickier they become".

[0011] Therefore, the present invention aims to provide a medical device biofilm prevention system based on low-energy surface acoustic waves to solve the above-mentioned problems. Summary of the Invention

[0012] The purpose of this invention is to provide a biofilm prevention system for medical devices based on low-energy surface acoustic waves. This invention interferes with the initial attachment of microorganisms through nanoscale surface acoustic wave vibration and microfluidic effects. It does not rely on any antibacterial drugs or chemical coatings, does not induce bacterial drug resistance, and its effects are reversible, without affecting the physiological activity of microorganisms. After the vibration stops, microorganisms recover their normal surface attachment ability within 10 minutes ± 4 minutes, with minimal impact on the microbial ecology. It is suitable for various indwelling devices such as urinary catheters and central venous catheters.

[0013] The above-mentioned technical objective of the present invention is achieved through the following technical solution: a medical device biofilm prevention system based on low-energy surface acoustic waves, comprising a piezoelectric vibration module, a vibration transmission module, a drive control module, and a power supply module;

[0014] The piezoelectric vibration module is used to be attached to or integrated into the wall of an indwelling medical device, and generates elastic vibration with a frequency of 100 kHz to 300 kHz and an amplitude of 300 nm to 800 nm in response to a driving electrical signal.

[0015] The vibration transmission module is acoustically coupled between the piezoelectric vibration module and the medical device, and is used to uniformly transmit the elastic vibration to the entire surface of the medical device, exciting surface acoustic waves with longitudinal and transverse components on the surface, and the final vibration amplitude of the surface is controlled within the range of 0.2 nm to 2 nm.

[0016] The drive control module, electrically connected to the piezoelectric vibration module, is used to generate and output periodic rectangular electrical pulses, and adjust the frequency, amplitude, and duty cycle of the electrical pulses so that the power density on the surface of the medical device is controlled at 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 Within the treatment window;

[0017] The power module includes a rechargeable battery unit and / or an external power interface, used to provide stable operating power to the drive control module and the piezoelectric vibration module.

[0018] The present invention is further configured such that the power density is 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 The treatment window is configured such that the surface acoustic waves exert a net repulsive effect on microorganisms within this range, inhibiting initial microbial attachment; while when the power density exceeds 0.35 mW / cm², the surface acoustic waves exert a net repulsive effect on microorganisms, inhibiting initial microbial attachment; and when the power density exceeds 0.35 mW / cm², the surface acoustic waves exert a net repulsive effect on microorganisms, inhibiting initial microbial attachment. 2 At that time, the surface acoustic waves will transform into a force that promotes microbial adhesion.

[0019] The present invention is further configured such that the drive control module includes:

[0020] A signal generating unit is used to generate the periodic rectangular electrical pulses;

[0021] A power amplifier unit is used to amplify the power of the electrical pulse;

[0022] An impedance matching unit is connected between the power amplifier unit and the piezoelectric vibration module to match the output impedance with the capacitive impedance of the piezoelectric vibration module.

[0023] The real-time monitoring and feedback control unit is used to monitor the operating parameters of the piezoelectric vibration module and dynamically adjust the output according to the monitoring results, so that the power density is maintained within the treatment window range.

[0024] The present invention is further configured such that: the piezoelectric vibration module is made of PZT series piezoelectric ceramic material, and the vibration transmission module is composed of medical silicone or epoxy resin that matches the acoustic impedance of the medical device matrix material.

[0025] The present invention is further configured such that the indwelling medical device is selected from urinary catheters, central venous catheters, endotracheal tubes or peritoneal dialysis tubes.

[0026] This invention also provides a method for preventing biofilm formation in medical devices based on low-energy surface acoustic waves, comprising the following steps:

[0027] S1. Attach or integrate the piezoelectric vibration module to the wall of the indwelling medical device and electrically connect it to the drive control module and the power module.

[0028] S2. The drive control module generates periodic rectangular electrical pulses with a frequency of 100 kHz to 300 kHz.

[0029] S3. The electrical pulse is amplified and impedance matched before being sent to the piezoelectric vibration module to drive it to generate elastic vibration with an amplitude of 300 nm to 800 nm.

[0030] S4. The elastic vibration is uniformly transmitted to the entire surface of the medical device through the acoustically coupled vibration transmission module, exciting surface acoustic waves with longitudinal and transverse components, and the final vibration amplitude of the surface is controlled within the range of 0.2 nm to 2 nm.

[0031] S5. Adjust the output power of the electrical pulse in real time to maintain the power density on the surface of the medical device at 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 Within the treatment window;

[0032] S6. During all or most of the time the medical device is in place, the surface acoustic waves are continuously or intermittently generated to form a microfluidic field that interferes with the initial attachment of planktonic microorganisms, thereby preventing biofilm formation.

[0033] The present invention is further configured such that step S5 further includes: when the power density is detected to be below 0.05 mW / cm² 2 Increase output power when it exceeds 0.20 mW / cm 2 When the output power is reduced, exceeding 0.35 mW / cm 2 The system will execute a security lock or alarm at any time.

[0034] The present invention is further configured such that, in step S6, the surface acoustic wave prevents biofilm formation through one or more combinations of the following physical mechanisms:

[0035] Mechanism I: The nanoscale vibration and microfluidic effect induced by the surface acoustic wave disrupts the balance of van der Waals forces and electrostatic interactions between microorganisms and the surface, preventing the initial attachment of microorganisms;

[0036] Mechanism II: The surface acoustic waves limit the vibration amplitude of microorganisms to within the effective range of the zeta potential repulsion layer at the solid-liquid interface, generating a net repulsive force;

[0037] Mechanism III: The microfluidic effect generated by the surface acoustic waves disrupts the quorum sensing molecular gradient around the microorganisms, hindering the transmission of communication signals between microorganisms and subsequent biofilm differentiation;

[0038] Mechanism IV: The power density of the surface acoustic wave is maintained below the threshold for activating the microbial FimH mechanoreceptors, thereby avoiding the effect of enhanced mechanoadhesion.

[0039] The present invention is further configured such that the intermittent is generated in a high-frequency intermittent mode of working for 10 seconds and then intermittently for 1 second.

[0040] The present invention is further configured such that the surface acoustic wave's inhibitory effect on microbial biofilms is as follows: in in vitro experiments, the biofilm load on the treated medical device surface is reduced by 0.75-1.22 log... 10 CFU / cm 2 In animal experiments, the time that the catheter equipped with the system kept urine sterile was extended from 2 days in the control group to 7.3 to 9 days in the treatment group.

[0041] In summary, the present invention has the following beneficial effects:

[0042] 1. This invention can significantly reduce biofilm load. In vitro experiments show that after treatment with this system, the microbial biofilm load on the surface of the urinary catheter is reduced by 0.75-1.22 log. 10 CFU / cm 2 (P<0.05) Scanning electron microscopy showed that there were almost no microorganisms attached to the surface; at the same time, it greatly extended the sterile use time in vivo. In the rabbit urethral catheter model, the catheter equipped with this system kept the urine sterile for up to 9 days (compared to only 2 days in the control group), and the time to urinary tract infection was delayed from 1.5 days to 7.3 days (P<0.0009).

[0043] 2. This invention interferes with the initial attachment of microorganisms through nanoscale surface acoustic wave vibration and microfluidic effect. It does not rely on any antibacterial drugs or chemical coatings, does not induce bacterial drug resistance, and the effect is reversible and does not affect the physiological activity of microorganisms. After the vibration stops, the microorganisms recover their normal surface attachment ability within 10 minutes ± 4 minutes, proving that this method is a reversible physical intervention with minimal impact on the microbial ecology.

[0044] 3. In this invention, the system precisely controls the power density within the range of 0.05-0.20 mW / cm². 2 Within a safe range, experiments have confirmed that once the power density exceeds 0.35 mW / cm², [the situation becomes unsafe]. 2 Instead, it activates the FimH mechanoreceptors of bacteria (such as E. coli), turning them into adhesion promoters. This invention actively avoids this threshold to ensure that it is always in the inhibition zone.

[0045] 4. The system of this invention shows significant biofilm inhibition effects against a variety of Gram-positive bacteria (such as Enterococcus faecalis), Gram-negative bacteria (such as Escherichia coli and Proteus mirabilis), and fungi (such as Candida albicans), and has a wide range of applications.

[0046] 5. Histological analysis in animal experiments showed that SAW treatment did not cause any damage or pathological changes to the urothelium or mucosa, but instead reduced catheter-related mechanical friction trauma, demonstrating good biocompatibility.

[0047] 6. This invention can be integrated into the device wall or detachably installed on the external segment as an independent accessory. It is applicable to various clinical indwelling devices such as urinary catheters, central venous catheters, endotracheal tubes, and peritoneal dialysis catheters, and has practical transformation and application value. Attached Figure Description

[0048] Figure 1 This is a schematic diagram of the module structure of the medical device biofilm prevention system based on low-energy surface acoustic waves in Embodiment 1 of the present invention;

[0049] Figure 2 This is a schematic diagram of the data flow of the medical device biofilm prevention system based on low-energy surface acoustic waves in Embodiment 1 of the present invention;

[0050] Figure 3 This is a schematic diagram of the process interaction of the medical device biofilm prevention system based on low-energy surface acoustic waves in Embodiment 1 of the present invention;

[0051] Figure 4 This is a schematic diagram of the structural framework of the medical device biofilm prevention system based on low-energy surface acoustic waves in Embodiment 1 of the present invention;

[0052] Figure 5 This is a schematic flowchart of the steps of the medical device biofilm prevention method based on low-energy surface acoustic waves in Embodiment 2 of the present invention. Detailed Implementation

[0053] The following is in conjunction with the appendix Figures 1-5 The present invention will be described in further detail below.

[0054] Example 1: A medical device biofilm prevention system based on low-energy surface acoustic waves, including a piezoelectric vibration module, a vibration transmission module, a drive control module, and a power supply module.

[0055] In this embodiment, the piezoelectric vibration module is made of PZT-5H piezoelectric ceramic sheet, which is rectangular in shape, 10 mm long, 5 mm wide, and 0.8 mm thick, with silver-plated electrodes on the surface. It is installed by tightly attaching it to the outer wall of the external segment of the catheter through a medical-grade silicone coupling layer. The silicone layer also serves as an adhesive and acoustic impedance matching layer.

[0056] The vibration transmission module is composed of the catheter wall and the fluid inside the catheter. The elastic vibration generated by the piezoelectric pad is transmitted to the catheter wall through the silicone coupling layer and propagates longitudinally along the catheter wall to the catheter balloon and tip, causing surface acoustic waves to be excited on the entire surface of the device.

[0057] The drive control module comprises the following four sub-units, which are connected in sequence:

[0058] Signal generation unit: generates periodic rectangular electrical pulses with a frequency of 100-300 kHz and an adjustable duty cycle.

[0059] Power amplifier unit: amplifies electrical pulse signals to a voltage and current sufficient to drive piezoelectric elements.

[0060] Impedance matching unit: Connected between the power amplifier unit and the piezoelectric vibration module, it matches the output impedance with the capacitive impedance of the piezoelectric element, thereby improving energy transmission efficiency.

[0061] Real-time monitoring and feedback control unit: Monitors the operating parameters of the piezoelectric vibration module (such as drive voltage and current), and dynamically adjusts the output power through a control algorithm to maintain the power density on the instrument surface at 0.05-0.20 mW / cm². 2 Inside the treatment window.

[0062] The logical connection relationship is as follows: signal generation unit → power amplification unit → impedance matching unit → piezoelectric vibration module; the real-time monitoring unit samples from the power output terminal and sends the feedback signal to the signal generation unit to form a closed-loop control.

[0063] Power module: It adopts a rechargeable lithium battery unit and can be equipped with an external power interface. This module provides stable working power for the drive control module and piezoelectric vibration module. The built-in battery supports continuous operation for more than 27 hours, and the intermittent mode can extend the battery life. The external power interface supports long-term continuous operation.

[0064] In this embodiment, the range of the system's core operating parameters is shown in Table 1:

[0065] Table 1 Core Parameter Range Table

[0066]

[0067] In this embodiment, the parameters are set via MCU programming, specifying the driving electrical pulse as a rectangular wave with a frequency of 200 kHz and a duty cycle of 50%. After impedance matching and power amplification, the piezoelectric ceramic generates elastic vibration with an amplitude of 500 nm. After in vitro pre-calibration, the surface acoustic wave amplitude excited by this vibration on the entire surface of the catheter (including the body, balloon, and tip) ranges from 0.5 to 1.8 nm, corresponding to a power density of 0.12 to 0.18 mW / cm².2 All were within the therapeutic window (0.05~0.20 mW / cm²). 2 )Inside.

[0068] The microcontroller samples the drive current and voltage every 100 ms to calculate the real-time power density.

[0069] If the calculated value is <0.08mW / cm 2 Gradually increase the PWM duty cycle (step size 1%).

[0070] If the calculated value is >0.20 mW / cm 2 Gradually reduce the duty cycle;

[0071] If the calculated value is >0.35mW / cm 2 (In case of abnormal situations, such as equipment falling off or short circuit) immediately shut off the output and trigger an audible and visual alarm.

[0072] In this preferred embodiment, the system is not only suitable for urinary catheters, but can also be adapted to other indwelling medical devices through simple parameter adjustments, as shown in Table 2:

[0073] Table 2 Adaptability Adjustment Table for Different Integrable Devices

[0074]

[0075] The specific adjustment method is as follows: by changing the size of the piezoelectric ceramic or adjusting the driving voltage, the final surface power density falls near the lower limit of the treatment window, and then fine-tunes it to the optimal value through real-time feedback.

[0076] Example 2: Biofilm Prevention Method for Medical Devices Based on Low-Energy Surface Acoustic Waves

[0077] This embodiment implements a medical device biofilm prevention method based on low-energy surface acoustic waves on the system of Embodiment 1, specifically including the following steps:

[0078] Step S1: System preparation and installation.

[0079] Step S101: Attach the piezoelectric vibration module (PZT-5H piezoelectric ceramic sheet, size 10mm×5mm×0.8mm) to the external segment of the Foley catheter (about 2 cm from the external port) using medical-grade silicone coupling agent, ensuring that the piezoelectric sheet is tightly attached to the catheter wall without air bubbles.

[0080] Step S102: Connect the electrode leads of the piezoelectric sheet to the output port of the drive control module (which has been pre-encapsulated in a waterproof box).

[0081] Step S103: Secure the drive control module to the patient's inner thigh or next to the external segment of the urinary catheter using medical double-sided tape or a bandage to avoid pulling on the catheter.

[0082] Step S104: Check the power module's charge level (3.7V / 500mAh lithium polymer battery). If the charge level is below 20%, charge it to 100% via the Micro-USB interface.

[0083] Step S2: Parameter initialization and calibration.

[0084] Step S201: Press and hold the power button on the drive control module for 3 seconds to power on and perform a self-test. The microcontroller (MCU) detects the resonant impedance of the piezoelectric element: if the impedance value is within the expected range (5–20 Ω), the green LED will remain lit, indicating that the system is normal; if the impedance is abnormal (such as open circuit or short circuit), the red LED will flash, prompting you to check the connection.

[0085] Step S202: After the self-test passes, the MCU reads the pre-stored calibration parameters from the EEPROM (determined based on the calibration results of this batch of catheters before leaving the factory), including:

[0086] Drive frequency: 200 kHz;

[0087] Initial drive voltage amplitude: ±32 V (corresponding to an expected surface power density of 0.15 mW / cm²) 2 );

[0088] Duty cycle: 50%;

[0089] Target power density: 0.15 mW / cm³ 2 ;

[0090] Permissible deviation: ±0.03 mW / cm 2 ;

[0091] Safety limit: 0.35 mW / cm 2 .

[0092] Step S203: If the catheter is different from the catheter used during calibration (e.g., different manufacturers, different sizes), the user can quickly perform on-site calibration via Bluetooth connection to a mobile APP: the system automatically increases the driving voltage in 5V increments while measuring the feedback current, and the software algorithm automatically matches the optimal parameters based on the impedance spectrum. The entire process takes about 30 seconds.

[0093] Step S3: Start surface acoustic wave output.

[0094] Step S301: Press the power button again briefly to enter the running mode; the MCU generates a 200 kHz rectangular pulse sequence through the DAC, which is amplified to the preset initial voltage (±32 V) by the power amplifier unit, and then drives the piezoelectric ceramic sheet through the impedance matching network.

[0095] In step S302, the piezoelectric ceramic sheet generates elastic vibrations in the thickness direction (amplitude approximately 500 nm). This vibration is transmitted to the catheter wall through the silicone coupling layer, propagates longitudinally along the catheter wall, and excites surface acoustic waves with an amplitude of 0.5-1.8 nm across the entire surface of the catheter (including the body, balloon, and tip). The surface acoustic waves simultaneously possess a longitudinal component (propagating along the instrument surface) and a transverse component (perpendicular to the surface and pointing towards the surrounding fluid).

[0096] Step S303: Surface acoustic waves induce microstreaming on the surface of the catheter and in the adjacent fluid layer, forming stable micron-sized vortices.

[0097] Step S4: Real-time power monitoring and closed-loop feedback control.

[0098] Step S401: The real-time monitoring unit collects the drive voltage and current at a period of 50 ms, and calculates the instantaneous output power density (unit: mW / cm²) using the following formula. 2 ):

[0099]

[0100] in, , These are the effective values ​​of the driving voltage and current, respectively. Electromechanical conversion efficiency (factory rated value); The surface area of ​​the urinary catheter (pre-stored in the MCU according to the model).

[0101] Step S402: The MCU compares the calculated power density with the target value (0.15 mW / cm²). 2 )Compare:

[0102] If the measured value is within ±0.03 mW / cm 2 Within the range (i.e., 0.12-0.18 mW / cm) 2 ), maintain the current driving parameters.

[0103] If the measured value is <0.12 mW / cm 2 The PI controller increases the DAC output value using a proportional-integral algorithm (1% step at a time), thereby increasing the drive voltage and raising the power density.

[0104] If the measured value is >0.18 mW / cm 2 Gradually reduce the DAC output value.

[0105] Step S403: The system simultaneously checks safety conditions.

[0106] If three consecutive measurements are >0.35 mW / cm 2(If an abnormality is detected, such as piezoelectric stripping or impedance sudden change, immediately shut off the power amplifier unit's enable terminal. The red LED will flash rapidly and a buzzer alarm will sound, prompting medical personnel to check.)

[0107] If the value is <0.03 mW / cm for 6 consecutive measurements 2 (Possibly due to a detached piezoelectric element or a broken wire), the system intermittently attempts to recover (attempting to drive for 1 second every 10 seconds), while a yellow LED flashes, indicating replacement or repair.

[0108] This step is used to ensure that the surface acoustic wave power density remains within the treatment window (0.05-0.20 mW / cm²). 2 Within this range, it can effectively inhibit the initial attachment of microorganisms while avoiding the problem of power exceeding 0.35 mW / cm. 2 And activate the FimH mechanism to enhance bacterial adhesion.

[0109] Step S5: Continuous or intermittent operation.

[0110] Based on the expected device indwelling time and patient activity needs, this step selects one of the following operating modes:

[0111] Mode 1: Continuous operation mode (recommended for short-term stay, ≤7 days).

[0112] The system continuously generates surface acoustic waves during the indwelling catheter period (e.g., 5-7 days). This mode provides optimal biofilm prevention and is suitable for patients at high risk of infection. In this mode, the measured power consumption is approximately 18 mA @ 3.7V, and a 500mAh battery can support approximately 27 hours; for longer periods, an external power bank (5V USB) can be connected, or a fully charged spare battery can be used daily.

[0113] Mode 2: Intermittent operation mode (recommended for medium- to long-term stays, >7 days)

[0114] To extend battery life while maintaining effective prevention, a cyclical mode of "10 seconds of operation followed by 1 second of rest" is adopted. Specific implementation method:

[0115] The timer in the MCU controls the enable pin (EN pin) of the power amplifier unit.

[0116] Each cycle lasts 11 seconds: for the first 10 seconds, EN is high, and the system outputs drive pulses normally; for the last second, EN is low, the power amplifier unit is turned off, and the piezoelectric element stops vibrating.

[0117] During the intermittent period, the real-time monitoring unit continues to collect current and voltage (the output is 0 at this time), but does not perform feedback adjustment; after the output is restored, the system stabilizes again near the target power density within 0.5 seconds.

[0118] Experimental results show that there is no statistically significant difference in biofilm inhibition between intermittent and continuous modes (P>0.05), but energy consumption is reduced by about 10%, and the battery life is extended from about 27 hours to about 30 hours.

[0119] Mode 3: Demand-Driven Mode (for specific scenarios)

[0120] The system can be linked with a urine flow sensor or a microbial sensor: it automatically activates the SAW when urine flow is detected or microbial concentration increases, and enters low-power standby (power consumption <1 μA) when there is no trigger. This mode is suitable for patients who need ultra-long-term indwelling (e.g., >28 days) and have a high risk of infection at different stages.

[0121] Step S6: Sterilization and shutdown.

[0122] Step S601: When the urinary catheter needs to be removed or the indwelling is finished, the medical staff press and hold the power button for 3 seconds to cut off the system output and enter sleep mode.

[0123] Step S602: Remove the drive control module from the patient and disconnect it from the piezoelectric pad. The piezoelectric pad can be discarded along with the urinary catheter (for single use) or reused after cleaning and ethylene oxide sterilization (the effect of sterilization on piezoelectric performance needs to be verified).

[0124] Step S603: If a new urinary catheter needs to be replaced on the same patient, a new piezoelectric pad (pre-attached to the new catheter) can be replaced and the original drive control module can be reconnected. The MCU will automatically re-detect the impedance and perform a quick adaptation (approximately 10 seconds).

[0125] Example 3: In vitro urinary catheter biofilm inhibition experiment

[0126] This embodiment is used to verify the preventive effect of the system in Example 1 on the formation of biofilms by common pathogenic microorganisms (bacteria and fungi) on the surface of the urinary catheter. The experimental materials are as follows:

[0127] Test equipment: 16Fr silicone latex Foley catheter, 6cm in length, integrated with the SAW system (experimental group) and the same unintegrated catheter (control group) as described in Example 1.

[0128] Microbial strains: Escherichia coli, Enterococcus faecalis, Candida albicans, Proteus mirabilis.

[0129] Culture medium: 50% tryptone soybean broth (TSB) + 50% sterile urine from healthy individuals + 8% fetal bovine serum.

[0130] In this embodiment, the experimental steps are as follows:

[0131] (1) Place the catheters of the experimental group and the control group into 25 mL tissue culture bottles and seal the bottle mouths.

[0132] (2) Incubate each microorganism overnight to the logarithmic phase and adjust the concentration to 10. 3 CFU / mL, injected into the culture flask.

[0133] (3) Use a peristaltic pump to continuously flow culture at 0.5 mL / min, and control the temperature at 30±1℃.

[0134] (4) The experimental group turned on the SAW system and worked continuously for 72 hours; the control group did not turn it on.

[0135] (5) Replace the culture medium with fresh culture medium every 24 hours.

[0136] (6) After 72 hours, remove the catheter and gently rinse it three times with PBS to remove any unadhered bacteria.

[0137] (7) Cut the catheter into 3 cm segments, place them in centrifuge tubes containing PBS, and sonicate twice at 20 kHz and 3-4 W (30 seconds each time) to wash away the adhering biofilm.

[0138] (8) After serial dilution, the samples were spread onto blood agar plates and incubated at 37°C for 24 hours. The colony-forming units (CFU / cm³) were then counted. 2 ).

[0139] (9) Another catheter segment was fixed with glutaraldehyde, dehydrated in a gradient, dried at the critical point, and sputtered with gold. The surface morphology was then observed under a scanning electron microscope.

[0140] The experimental results are shown in Table 3:

[0141] Table 3 Effects of SAW treatment on biofilm load on urinary catheter surface

[0142]

[0143] This embodiment also shows through scanning electron microscopy (SEM) that the surface of the ducts in the SAW-treated group was almost free of visible microbial adhesion and was smooth and clean; while the surface of the ducts in the control group was covered with dense microbial colonies and extracellular matrix, forming a mature biofilm structure.

[0144] Example 4: Biofilm preventive effect in a rabbit in vivo urethral catheter model

[0145] This embodiment is used to verify in a live animal model whether the system in Example 1 can delay or prevent catheter-related urinary tract infections. The experimental animals and their groups are as follows:

[0146] Animals: 8 New Zealand White rabbits, 3-4 months old, weighing 3.5-5.5 kg, male.

[0147] Grouping: The participants were randomly divided into a SAW treatment group (n=4) and a control group (n=4).

[0148] In this embodiment, the experimental steps are as follows:

[0149] (1) Catheter preparation: A 10Fr silicone latex Foley catheter was used, and the SAW system was integrated into the external segment of the catheter as described in Example 1. The control group catheter was made of the same material but without the SAW system.

[0150] (2) Surgical insertion: After anesthetizing the animal with a mixture of ketamine / xylazine (0.7 mL / kg), the perineum was disinfected, and the catheter was inserted into the bladder through the urethra under aseptic conditions. The balloon was then injected with 3-4 mL of sterile saline for fixation.

[0151] (3) System activation: The system is activated immediately after the SAW group catheter is inserted, and the parameters are set the same as in Example 1 (surface power density 0.12-0.18 mW / cm²). 2 The animals were kept in the duct for 9 days or until they were removed due to infection. The control group showed no activation of the catheter.

[0152] (4) Postoperative management: The animals wear a special harness with a catheter connected to a sterile urine collection bag, which is changed daily. Urine samples are collected daily, continuously diluted and spread on blood agar, and colonies are counted after 24 hours.

[0153] (5) Exclusion criteria: Urine bacterial count >10 5 A concentration of CFU / mL is considered bacteriuria, and the animal is terminated from the experiment (in accordance with animal ethics requirements).

[0154] (6) Histological examination: At the end of the experiment, the animals were euthanized by overdose of anesthesia, and the bladder and urethra were removed. The catheters were collected, and some of the catheters were used for SEM observation and some for biological load quantification. The bladder tissue was stained with hematoxylin and eosin to assess epithelial integrity and inflammatory response.

[0155] The experimental results are shown in Table 4:

[0156] Table 4. Occurrence of bacteriuria in various animals (>10) 5 Time (days) for CFU / mL)

[0157]

[0158] The average time to infection in the SAW-treated group was 7.3 days, while that in the control group was 1.5 days, with a highly statistically significant difference (P<0.0009, two-tailed t-test). Furthermore, the urine of both SAW-treated animals remained sterile throughout the 9-day and 7-day experimental periods.

[0159] After the experiment, the catheters were recovered. In this embodiment, the scanning electron microscope (SEM) showed that there were very few bacteria or yeasts adhering to the inner and outer surfaces of the catheters in the SAW treatment group, and the surface was basically clean. In contrast, the surface of the catheters in the control group (especially the balloon and tip) was covered with a thick biofilm, including a large number of bacilli, cocci and extracellular polysaccharide matrix.

[0160] Bladder tissue sections showed that the urothelium in the SAW-treated group was intact, with no obvious inflammatory cell infiltration in the submucosa, and no significant difference from normal tissue. Interestingly, some areas in the control group showed epithelial sloughing, erosion, and moderate inflammatory response, which were considered to be related to catheter-related mechanical friction and infection. This indicates that this system not only did not cause additional damage, but may have reduced catheter-related tissue trauma by inhibiting infection.

[0161] Example 5: Validation Experiment of Mechanobiological Threshold of FimH-Mediated Adhesion

[0162] This embodiment reveals the mechanism by which surface acoustic waves of different power densities have opposing effects on microbial adhesion, and is used to verify the therapeutic window energy range (0.05-0.20 mW / cm²) set in the system of Example 1. 2 The necessity of ).

[0163] In this embodiment, the experimental method is as follows:

[0164] Model: Uropathogenic Escherichia coli (clinical isolate expressing type I fimbriae and FimH adhesin) + guinea pig erythrocytes (4% suspension).

[0165] Apparatus: Attach the SAW piezoelectric actuator to the bottom of a 50 mm petri dish, and add bacteria (10⁻⁶) to the petri dish. 9 (CFU / mL) and red blood cell suspension.

[0166] Grouping: Different power density groups were established: 0 (control group), 0.05, 0.10, 0.20, 0.35, 0.50, and 0.70 mW / cm². 2 The frequency is fixed at 150 kHz.

[0167] Observation indicators: Observe the aggregation of red blood cells under a microscope (reflecting the strength of bacterial-red blood cell adhesion) and record the results by photograph. 50 mM D-mannose was added to some groups to verify specificity.

[0168] The experimental results are as follows:

[0169] When the power density is between 0.05 and 0.20 mW / cm² 2Within the therapeutic window: no erythrocyte aggregation was observed within 3 hours, similar to the negative control group (no SAW and no bacteria); erythrocyte aggregation began to appear approximately 10 ± 4 minutes after SAW cessation, indicating that the inhibition was reversible.

[0170] When the power density is 0.35 mW / cm 2 At this time: a small number of red blood cells begin to aggregate.

[0171] When power density ≥ 0.50 mW / cm 2 Within 15 minutes, a large number of dense red blood cells appeared, with aggregates reaching the millimeter in diameter. These aggregates could be completely dissociated by 50 mM D-mannose, proving that they were mediated by FimH-mannose-specific adhesion.

[0172] Power density ≥ 0.35 mW / cm³ 2 The mechanism of the enhanced effect: The shear force induced by high-power SAW activates the mechanoreceptor function of FimH, causing the bacteria to change from "loose rolling" to "tight anchoring", which in turn promotes adhesion.

[0173] Conclusion: This application precisely controls the SAW power density within the range of 0.05-0.20 mW / cm². 2 The low-energy range ensures both the effectiveness of inhibiting initial microbial attachment and actively avoids high-power (≥0.35 mW / cm²) areas. 2 By using force to enhance adhesion in the "trap zone," a safe and effective physical biofilm prevention method is achieved.

[0174] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A medical device biofilm prevention system based on low-energy surface acoustic waves, characterized in that: It includes a piezoelectric vibration module, a vibration transmission module, a drive control module, and a power supply module; The piezoelectric vibration module is used to be attached to or integrated into the wall of an indwelling medical device, and generates elastic vibration with a frequency of 100 kHz to 300 kHz and an amplitude of 300 nm to 800 nm in response to a driving electrical signal. The vibration transmission module is acoustically coupled between the piezoelectric vibration module and the medical device, and is used to uniformly transmit the elastic vibration to the entire surface of the medical device, exciting surface acoustic waves with longitudinal and transverse components on the surface, and the final vibration amplitude of the surface is controlled within the range of 0.2 nm to 2 nm. The drive control module, electrically connected to the piezoelectric vibration module, is used to generate and output periodic rectangular electrical pulses, and adjust the frequency, amplitude, and duty cycle of the electrical pulses so that the power density on the surface of the medical device is controlled at 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 Within the treatment window; The power module includes a rechargeable battery unit and / or an external power interface, used to provide stable operating power to the drive control module and the piezoelectric vibration module.

2. The medical device biofilm prevention system based on low-energy surface acoustic waves according to claim 1, characterized in that: The power density is 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 The treatment window is configured such that the surface acoustic waves exert a net repulsive effect on microorganisms within this range, inhibiting initial microbial attachment; while when the power density exceeds 0.35 mW / cm², the surface acoustic waves exert a net repulsive effect on microorganisms, inhibiting initial microbial attachment; and when the power density exceeds 0.35 mW / cm², the surface acoustic waves exert a net repulsive effect on microorganisms, inhibiting initial microbial attachment. 2 At that time, the surface acoustic waves will transform into a force that promotes microbial adhesion.

3. The medical device biofilm prevention system based on low-energy surface acoustic waves according to claim 1, characterized in that: The drive control module includes: A signal generating unit is used to generate the periodic rectangular electrical pulses; A power amplifier unit is used to amplify the power of the electrical pulse; An impedance matching unit is connected between the power amplifier unit and the piezoelectric vibration module to match the output impedance with the capacitive impedance of the piezoelectric vibration module. The real-time monitoring and feedback control unit is used to monitor the operating parameters of the piezoelectric vibration module and dynamically adjust the output according to the monitoring results, so that the power density is maintained within the treatment window range.

4. The medical device biofilm prevention system based on low-energy surface acoustic waves according to claim 1, characterized in that: The piezoelectric vibration module is made of PZT series piezoelectric ceramic material, and the vibration transmission module is made of medical silicone or epoxy resin that matches the acoustic impedance of the medical device matrix material.

5. The medical device biofilm prevention system based on low-energy surface acoustic waves according to claim 1, characterized in that: The indwelling medical device is selected from urinary catheters, central venous catheters, endotracheal tubes, or peritoneal dialysis catheters.

6. A method for preventing biofilm formation in medical devices based on low-energy surface acoustic waves, applied to any one of the low-energy surface acoustic waves-based biofilm prevention systems in medical devices according to claims 1-5, characterized in that: Includes the following steps: S1. Attach or integrate the piezoelectric vibration module to the wall of the indwelling medical device and electrically connect it to the drive control module and the power module. S2. The drive control module generates periodic rectangular electrical pulses with a frequency of 100 kHz to 300 kHz. S3. The electrical pulse is amplified and impedance matched before being sent to the piezoelectric vibration module to drive it to generate elastic vibration with an amplitude of 300 nm to 800 nm. S4. The elastic vibration is uniformly transmitted to the entire surface of the medical device through the acoustically coupled vibration transmission module, exciting surface acoustic waves with longitudinal and transverse components, and the final vibration amplitude of the surface is controlled within the range of 0.2 nm to 2 nm. S5. Adjust the output power of the electrical pulse in real time to maintain the power density on the surface of the medical device at 0.05 mW / cm². 2 Up to 0.20 mW / cm 2 Within the treatment window; S6. During all or most of the time the medical device is in place, the surface acoustic waves are continuously or intermittently generated to form a microfluidic field that interferes with the initial attachment of planktonic microorganisms, thereby preventing biofilm formation.

7. The method for preventing biofilm formation in medical devices based on low-energy surface acoustic waves according to claim 6, characterized in that: Step S5 further includes: when the power density is detected to be below 0.05 mW / cm² 2 Increase output power when it exceeds 0.20 mW / cm 2 When the output power is reduced, exceeding 0.35 mW / cm 2 The system will execute a security lock or alarm at any time.

8. The medical device biofilm prevention method based on low-energy surface acoustic waves according to claim 6, characterized in that: In step S6, the surface acoustic waves prevent biofilm formation through one or more combinations of the following physical mechanisms: Mechanism I: The nanoscale vibration and microfluidic effect induced by the surface acoustic wave disrupts the balance of van der Waals forces and electrostatic interactions between microorganisms and the surface, preventing the initial attachment of microorganisms; Mechanism II: The surface acoustic waves limit the vibration amplitude of microorganisms to within the effective range of the zeta potential repulsion layer at the solid-liquid interface, generating a net repulsive force; Mechanism III: The microfluidic effect generated by the surface acoustic waves disrupts the quorum sensing molecular gradient around the microorganisms, hindering the transmission of communication signals between microorganisms and subsequent biofilm differentiation; Mechanism IV: The power density of the surface acoustic wave is maintained below the threshold for activating the microbial FimH mechanoreceptors, thereby avoiding the effect of enhanced mechanoadhesion.

9. The method for preventing biofilm formation in medical devices based on low-energy surface acoustic waves according to claim 6, characterized in that: The intermittent is generated in a high-frequency intermittent mode of working for 10 seconds and then intermittently for 1 second.

10. The method for preventing biofilm formation in medical devices based on low-energy surface acoustic waves according to claim 6, characterized in that: The surface acoustic waves exhibited the following inhibitory effect on microbial biofilms: in in vitro experiments, the biofilm load on the treated medical device surface decreased by 0.75-1.22 log... 10 CFU / cm 2 In animal experiments, the time that the catheter equipped with the system kept urine sterile was extended from 2 days in the control group to 7.3 to 9 days in the treatment group.

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