Acoustic Mechanism And Applications Of Microbial Bacteria Prevention Using Ultrasound

Indwelling devices are widely used in clinical treatments,such as entrocheal tubes,catheter tubes,gastric intubation,prosthetic devices and other surgical implants,etc.Unfortunately,bacteria will attach to the surface and grow as a biofilm,which are protected from being killed by antibiotics.It is increasingly recognized as a key factor in the persistence of varied infections.Many efforts have been made to develop chemical and mechanical approaches for biofilm prevention.Catheters coated with specified antimicrobial materials,including hydrogel,silver salts,silver nanoparticles and antimicrobials,etc.,have been proven effective.Nevertheless,biofilms could still emerge,especially on catheters that remain inside bodies for relatively long periods,e.g.,urinary catheters and endotracheal tubes.Ultrasonic guided wave(UGW)has the characteristics of propagation along the surface of the tube,and it has shown promising for biofilm prevention.Up to now,it is required to deeply understand the acoustic mechanism of biofilm prevention,i.e.,relations of propagation mode,amplitude and frequencyof UGW to the effect of biofilm prevention,which is crucial for the development of implantable catheter.In this thesis,we discussed the acoustic mechanism and the applicationof ultrasound on preventing bacteria and biofilm from two following aspects:(1)The widely used Endotracheal tubes(ETs)wereused as research objects,and the effectof driving parameters of UGW(i.e.frequency and amplitude)on the capability of biofilm prevention was investigated.Firstly,we introduced the theory of UGW propagation,and found that there exist several propagation modeson ETs.We optimized the driving frequency based on the calculation of UGW propagation modes.Secondly,we measured the vibration on the surfaces of ETs,and found the significant attenuations.Consequently,we optimized the experimental setup via various strategies,including the use of the coupling agent and the change of incident angle.After being optimized,the measured amplitude of the acoustic vibrationcould be improved by 15-20 dB(>5 nm).Finally,the optimized setup was used to prevent P.aeruginosa biofilm formation.The prevention of biofilm formation was discussed with respect to varied vibration amplitudes.The experimental results demonstrated that the effects of biofilm prevention wasproportional to the vibration amplitude within the range of 50 pm to 5 nm,which suggestedthe effectiveness of the UGW on biofilms prevention.(2)Ultrasound wasexperimentally used to enhance the deliverypenetration for twosimulated antibacterial drugs.One was fluorescent nanoparticles,which has the similar size of nano sliver,commonly used antibacterial drugs coated on the surface of catheter tube;Another was medical hyaluronic acid(HA)with long chain structure and large molecular weight;it could simulate the adhesion of bacteria and drugs in the real environment.In the present work,ultrasound-facilitated topical drug delivery(TDD)was studied under various acoustic parameters,including frequency(20kHz,200kHz,643.5kHz,1MHz),amplitude(25kPa,50kPa,75kPa,100kPa),and exposure time(5mins to 60mins).The results measuredby laser confocal microscopyand ultraviolet spectrometry showed that ultrasound exposures could improve the permeability,includingthe penetration depth and the delivery concentration.Furthermore,the lower driving frequency could benefit the efficiency of drug delivery,but the penetration depth was less likely to exceed 200 ?m for all used frequencies.Moreover,we introduced microbubbles to improve the ultrasound-induced microbubble cavitation effect.The results showed that both the penetration depth and concentration weresignificantly enhanced.The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 500 ?m,and the penetration concentrations of fluorescent nanoparticles and HAwereincreased up to about 3-5 folds,and 7-8 folds,respectively.In this thesis,the effect of biofilms prevention using the UGW was studied firstly,and the resultsshowed that the acoustic mechanism is based on the mechanical vibration induced by guided wave propagation.Meanwhile,the relationship between the prevention effect with the parameters(propagation mode,frequency and amplitude)was studied.Secondly,ultrasound-facilitated TDD was studied,and better drug penetration depth and concentration were obtained by microbubble enhanced cavitation effect.This work provided new physical methods for clinical antibacterial,which was helpful for the development of new medical devices.