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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Targeting of stones and identification of stone fragmentation in shock wave lithotripsy /

Owen, Neil R., January 2007 (has links)
Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 73-87).
2

A study of stone fragmentation in shock wave lithotripsy by customizing the acoustic field and waveform shape

Chitnis, Parag Vijay January 2007 (has links)
Shock wave lithotripsy is the preferred treatment modality for kidney stones in the United States. Despite clinical use for over twenty-five years, the mechanisms of stone fragmentation are still under debate. A piezoelectric array was employed to examine the effect of waveform shape and pressure distribution on stone fragmentation in lithotripsy. The array consisted of 170 elements placed on the inner surface of a 15 cm-radius spherical cap. Each element was driven independently using a 170 individual pulsers, each capable of generating 1.2 kV. The acoustic field was characterized using a fiber optic probe hydrophone with a bandwidth of 30 MHz and a spatial resolution of 100 μm. When all elements were driven simultaneously, the focal waveform was a shock wave with peak pressures p+ =65±3MPa and p−=−16±2MPa and the −6 dB focal region was 13 mm long and 2 mm wide. The delay for each element was the only control parameter for customizing the acoustic field and waveform shape, which was done with the aim of investigating the hypothesized mechanisms of stone fragmentation such as spallation, shear, squeezing, and cavitation. The acoustic field customization was achieved by employing the angular spectrum approach for modeling the forward wave propagation and regression of least square errors to determine the optimal set of delays. Results from the acoustic field customization routine and its implications on stone fragmentation will be discussed. / National Institutes of Health DK043881
3

Studies on Customer Relations Management and Medical service satisfication under BOT Structure

Lee, Chi-liang 22 July 2009 (has links)
With the high development of society and economy, the rising level of national education, and the awareness of consumer rights in Taiwan, consumers¡¦ demands for medical and health care is increasing. The role of consumers has transformed to actively select and require medical and health care. The implementation of the National Health Insurance leads to the role change of the medical provider from a price maker to a price receiver, which benefits hospitals with mass product and cost control. Therefore, price-drive medical consumers become quality¡Vdriven ones, which benefits hospitals with good faculty, facilities and service. Nowadays, the hospital business environment is becoming more and more competitive. It is vital not only for hospital substantial business to create customer value of service and quality but also for hospital competitiveness to satisfy customer needs. The business strategy of hospitals is to greatly strengthen internal management and actively seek for the interaction with the external environment to keep survival and growth. Besides, hospitals apply CRM in order to attract new customers, retain old customers and to increase the profits of the customer contribution. Because of the limit of cost and budget tight policy, large hospitals are increasing their scale and the limited resource /number of customers. In this case, it is necessary for hospital¡¦s business strategy to focus on both quality and cost effectiveness. Hospitals build the tight relationship with customers so that they are willing to be diagnosed. Thus, Customer Relationship Management is the core competitive advantage for hospitals. Nevertheless, hospitals are less willing to purchase extracorporeal shock wave lithotripsy machines for the sake of the tight finance budget. As far as medical device suppliers are concerned, they have to adopt BOT approach in order to maintain business growth. Regarding the medical service and cooperation model for renal calculus patients, we discover that it is the equipment suppliers that are responsible for CRM rather than hospitals establishment. The retention number and returning frequency is the key to the revenues of the equipment suppliers, which means the relationship between hospitals and suppliers are unbroken. Our research indicates that the business model of extracorporeal shock wave lithotripsy machine can apply the concept of CRM. The medical equipment business and medical organization develop the model of the patient service with the base; CRM, the core value: customers and the hospital vision. We construct the ¡§four wins¡¨ model for the hospital, the patient, the Health Insurance Bureau and the business with the decision-making strategy, customer service and IT application.
4

Extracorporeal shock wave lithotripsy: how can we further optimeze its results?. / CUHK electronic theses & dissertations collection

January 2010 (has links)
Conclusion This series of investigations demonstrated how we can apply our knowledge to improve the treatment outcome of ESWL. Based on clinical information, such as age, suitable candidates for ESWL can be identified, and hence better application of ESWL can be achieved. With an understanding of the benefits and limitations of imaging (NCCT and intravenous urography), treatment success can be predicted, and better treatment plans for patients can be formulated. A policy of more liberal use of analgesia during ESWL can also help to improve the treatment outcomes of patients. Finally, with the use of different assessment methods, the true impact of various new technologies or treatment protocols can be assessed, and the results can lead to better understanding of ESWL and also improvement in the treatment outcomes. / Materials and Methods In a retrospective review of treatment information of 2192 patients, the effect of age on stone-free rates after ESWL was assessed. Next, in a prospective study, the role of stone parameter, measured using non-contrast computerized tomography (NCCT), in predicting the treatment outcomes of upper ureteric stones was examined. The general applicability of caliceal pelvic height (CPH) in determining the treatment outcomes for lower caliceal stones for three different lithotriptors was assessed in the third study. In another retrospective comparative study, the effect on treatment outcomes of additional usage of intravenous analgesic during ESWL, as compared to oral analgesic premedication alone, was analyzed. Finally, the feasibility of the use of two statistical methods, logistic regression and matched-pair analysis, in comparing the treatment results of different lithotriptors was investigated. / Objectives Despite the initial success of extracorporeal shock wave lithotripsy (ESWL), the performance of the contemporary machines has never been as good as that of the first-generation machine. Therefore, a series of studies was conducted to advance the current knowledge of ESWL and investigate possible ways to further optimize the treatment outcomes. / Results We found that the stone-free rate after ESWL for older patients with renal stones, but not for those with ureteric stones, was significantly lower than that of younger patients. Stone parameters measured using NCCT, namely, mean stone density, stone volume, and skin-to-stone distance, were significant predictive factors for successful ESWL for upper ureteric stones. However, caliceal pelvic height, measured by intravenous urography, was a significant predictor of treatment outcomes of lower caliceal stones for only the Piezolith 2300 lithotriptor, and not the other two types of lithotriptors. The additional usage of intravenous analgesic improved the effectiveness quotient and hence treatment outcomes of ESWL. Finally, both logistic regression and matched-pair analysis were found to be feasible approaches for the comparison of the performance of different lithotriptors. / Chi-Fai Ng. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 224-243). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
5

Adaptable Design Improvements For Electromagnetic Shock Wave Lithotripters And Techniques For Controlling Cavitation

Smith, Nathan Birchard January 2012 (has links)
<p>In this dissertation work, the aim was to garner better mechanistic understanding of how shock wave lithotripsy (SWL) breaks stones in order to guide design improvements to a modern electromagnetic (EM) shock wave lithotripter. To accomplish this goal, experimental studies were carefully designed to isolate mechanisms of fragmentation, and models for wave propagation, fragmentation, and stone motion were developed. In the initial study, a representative EM lithotripter was characterized and tested for in vitro stone comminution efficiency at a variety of field positions and doses using phantom kidney stones of variable hardness, and in different fluid mediums to isolate the contribution of cavitation. Through parametric analysis of the acoustic field measurements alongside comminution results, a logarithmic correlation was determined between average peak pressure incident on the stone surface and comminution efficiency. It was also noted that for a given stone type, the correlations converged to an average peak pressure threshold for fragmentation, independent of fluid medium in use. The correlation of average peak pressure to efficacy supports the rationale for the acoustic lens modifications, which were pursued to simultaneously enhance beam width and optimize the pulse profile of the lithotripter shock wave (LSW) via in situ pulse superposition for improved stone fragmentation by stress waves and cavitation, respectively. In parallel, a numerical model for wave propagation was used to investigate the variations of critical parameters with changes in lens geometry. A consensus was reached on a new lens design based on high-speed imaging and stone comminution experiments against the original lens at a fixed acoustic energy setting. The results have demonstrated that the new lens has improved efficacy away from the focus, where stones may move due to respiration, fragmentation, acoustic radiation forces, or voluntary patient movements. Using traditional theory of brittle fragmentation and newfound understanding of average peak pressure correlation to stone comminution, the entire set of stone comminution data for lens comparison was modeled using a Weibull-style distribution function. This model linked both the average peak pressure and shock wave dose to efficacy, including their respective threshold parameters, and demonstrated correlation of coefficients to cavitation activity. Subsequently, this model was used in prediction of stone comminution efficiency from mimicked respiratory motions in vitro, which compared favorably to actual simulated motion studies using both the new and original lenses. Under a variety of mimicked respiratory motions, the new lens produced statistically higher stone comminution efficiency than the original lens. These results were confirmed in vivo in a swine model, where the new lens produced statistically higher stone comminution after 1,000 and 2,000 shocks. Finally, a mechanistic investigation into the effects of cavitation with the original lens was conducted using an integrated, self-focusing annular ring transducer specially designed for tandem pulse lithotripsy. It was found that cavitation and stone comminution efficiency are progressively enhanced by tandem pulsing as source energies of both the primary LSW and trailing pressure pulse increase, which suggests cavitation and stress waves act synergistically enhance the efficacy in kidney stone fragmentation.</p> / Dissertation
6

The study on patient-oriented competitive strategy for extracorporeal shock wave lithotripsy

Wang, Chiang-Ting 02 July 2010 (has links)
The enforcement of national health insurance brings the new transition of medical service. The main purpose of this study is to investigate patients¡¦ emphasis and satisfaction on different dimension of service quality. The study referred to industrial views, related literature review and 5Qs model (Zineldin, 2006). Eventually, the practical research results are used to conduct a competitive niche strategy and a positioning plan of extracorporeal shock wave lithotripsy market to seek the unique value of medical service differentiation. According to the empirical view, the satisfaction and loyalty of those patients who had operations under the hospital treatment were significantly higher than those patients who didn¡¦t. ¡§Quality of atmosphere¡¨ and ¡§Quality of infrastructure¡¨ were the two factors which had positive impact on the satisfaction of patients. Also, ¡§Quality of medical care interaction¡¨ and ¡§Quality of atmosphere¡¨ affected the loyalty of patients greatly. Therefore, this study suggested that doctors should provide professional medical services to offer unique attributes which were valued by patients, and then achieved the influence of word-of-mouth marketing. The Competitive strategy is (1) from standardization to differentiation: creating values to patients by standard operation procedure. (2) from selfish departmentalism to patient-orientation: providing more interactions during medical service to fulfill the cognitive and emotional needs of patients. (3) from tradition to innovation: carrying out a new model which was designed by whole new ideas to supply medical service with sustainable competitive advantage. (4) from closed to open environment: emphasizing on profession and abandoning asymmetric information to develop trust relationship between doctors and patients. The strategic positioning of ESWL is to provide cordial, effective and fast integrated medical service for patients, and the establishment of ¡§Shock Wave Lithotripsy Center¡¨ is the further step of this strategy.
7

Non-axisymmetric and Steerable Acoustic Field for Enhanced Stone Comminution in Shock Wave Lithotripsy

Lautz, Jaclyn Mary January 2014 (has links)
<p>The primary goal of this dissertation was to assess the feasibility of transforming an electromagnetic (EM) shock wave lithotripter with an acoustic lens as its focusing device from the original axisymmetric pressure distribution to a non-axisymmetric steerable acoustic field. This work was motivated by the desire to better match the distribution of effective acoustic pressure and pulse energy with the trajectory and anatomical features around renal and ureteral calculi during clinical shock wave lithotripsy (SWL). The acoustic field transformation was accomplished by the design of a fan-shaped acoustic barrier (mask) placed on top of the lithotripter acoustic lens to selectively reduce the source aperture along the direction of the barrier axis, therefore effectively broadening the beam width (<italic>BW</italic>) of the lithotripter field in this preferred direction. Moreover, the geometry of the original lens (L<sub>1</sub>) was modified so that the acoustic focus of the new lens (L<sub>2</sub>) at high output voltages (necessitated by the incorporation of the mask) is closely aligned with the lithotripter focus. The mask was further driven by a motor-controlled gear system to rotate around the lithotripter axis, generating a steerable and non-axisymmetric acoustic field. In this dissertation project, a linear acoustic model was first used for parametric studies to assess the effects of mask geometry (opening angle and thickness) on beam elongation and peak pressure reduction. Based on this analysis, two mask geometries (L<sub>2</sub>+M<sub>8025</sub> and L<sub>2</sub>+M<sub>9030</sub>) were selected for modest and maximum beam elongation within the acceptable output range of the shock wave source. The acoustic and cavitation fields of the new lens with masks, as well as the corresponding field produced by the original lens, were characterized using fiber optical probe hydrophone measurements and stereoscopic high-speed imaging. Different output voltage settings were used for each lens configuration (i.e., 14 kV for L<sub>1</sub>, 15.8 kV for L<sub>2</sub>+M<sub>8025</sub>, and 17 kV L<sub>2</sub>+M<sub>9030</sub>) to produce equivalent acoustic pulse energy of 45 mJ in all setups, measured in the lithotripter focal plane. Under this condition, L<sub>2</sub>+M<sub>8025</sub> and L<sub>2</sub>+M<sub>9030</sub> generate lower peak pressure (38.2 and 36.8 MPa) with a significantly broadened BW<sub>y</sub> (11.4 and 14.3 mm) along the y-axis (head-to-toe direction of the patient), which is aligned with the mask axis, compared to the high peak pressure (44.1 MPa) and moderate <italic>BW</italic> (7.5 mm) of L<sub>1</sub>. It is worth noting that L<sub>2</sub>+M<sub>8025</sub> and L<sub>2</sub>+M<sub>9030</sub> produce a <italic>BW</italic><sub>x</sub> (7.6 and 7.5 mm) in the orthogonal direction to the mask axis, which is also comparable to L<sub>1</sub>. Similarly, the beam width of the cavitation field was broadened from 8.1 to 12.2 mm for L<sub>2</sub>+M<sub>8025</sub>, and from 10.9 to 17.9 mm for L<sub>2</sub>+M<sub>9030</sub>, compared to the range of 8.8 to 9.4 mm measured from L<sub>1</sub>. In comparison, L<sub>2</sub>+M<sub>8025</sub> produces a denser and narrower bubble cloud along the y-axis than L<sub>2</sub>+M<sub>9030</sub>. In vitro stone comminution (<italic>SC</italic>) tests in a tube holder (Diameter = 14 mm) have demonstrated that L<sub>2</sub>+M<sub>8025</sub> and L<sub>2</sub>+M<sub>9030</sub> are more effective at off-axis positions and during simulated respiratory motion along the elongated beam direction. The results of <italic>SC</italic> also confirmed the correlation between <italic>SC</italic> and the average peak pressure, p<sub>+(avg)</sub>, and effective acoustic pulse energy, E<sub>eft</sub>, delivered to the stone, as shown in previous studies. Furthermore, a ureter model was developed and used to assess the performance of L<sub>2</sub>+M<sub>9030</sub>, which has the maximally elongated <italic>BW</italic> under various static and simulated respiratory motion conditions. The results suggest that L<sub>2</sub>+M<sub>9030</sub> can produce significantly better <italic>SC</italic> than L<sub>1</sub> when the elongated beam is effectively aligned with the stone/fragments in the ureter or with their motion trajectory during the course of SWL treatment. Altogether, the results of this dissertation work have demonstrated <italic>in vitro</italic> that a non-axisymmetric and steerable acoustic field can significantly enhance stone comminution under clinically relevant SWL conditions. Future work is warranted to optimize the mask design and steering protocol to maximize the benefit of such an adaptable and versatile design to improve the performance and safety of clinical EM lithotripters.</p> / Dissertation
8

The effect of shock wave delivery rate on stone clearance, pain tolerance and renal injury in extracorporeal shock wave lithotripsy. / 沖擊波輸出頻率在體外沖擊波碎石治療的治療成效、病人對治療忍耐程度和對腎臟創傷的影響 / Chong ji bo shu chu pin lu zai ti wai chong ji bo sui shi zhi liao de zhi liao cheng xiao, bing ren dui zhi liao ren nai cheng du he dui shen zang chuang shang de ying xiang

January 2011 (has links)
by Lo, Kin Yin Anthony. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 168-195). / Abstracts in English and Chinese. / Abstract --- p.i / Declaration --- p.V / Publications and Conference Presentations --- p.vi / Scholarships and Awards --- p.vii / Acknowledgements --- p.viii / Table of contents --- p.X / Abbreviations --- p.xiv / List of Figures --- p.xvi / List of Tables --- p.xvii / Chapter 1. --- General Introduction --- p.1 / Chapter 2. --- Literature Review --- p.7 / Chapter 2.1 --- Introduction of nephrolithasis and surgical management --- p.9 / Chapter 2.1.1 --- Epidemology and physiochemistry --- p.9 / Chapter 2.1.2 --- Surgical management of nephrolithasis parallel with stone factors --- p.15 / Chapter 2.2 --- Extracorpoeral Shock Wave Lithotripsy in present study --- p.17 / Chapter 2.2.1 --- The 4th generation - Sonolith Vision electroconductive lithotripter --- p.18 / Chapter 2.2.2 --- The role of shock wave delivery rate in treatment outcome and its prediction --- p.23 / Chapter 2.2.3 --- Patient-controlled analgesia during Shock Wave Lithotripsy treatment and its pain management --- p.29 / Chapter 2.2.4 --- Shock wave induced renal injury & the use of urinary biomarker --- p.35 / Chapter 3. --- Materials and Methods --- p.62 / Chapter 3.1 --- Study Design --- p.63 / Chapter 3.2 --- Patient Selection --- p.64 / Chapter 3.3 --- Treatment Protocol --- p.63 / Chapter 3.4 --- Sample size calculation --- p.68 / Chapter 3.5 --- Statistical analysis --- p.68 / Chapter 4. --- The effect of shock wave delivery rate on treatment outcome and its prediction --- p.69 / Chapter 4.1 --- Introduction --- p.70 / Chapter 4.2 --- Materials and Methods --- p.72 / Chapter 4.2.1 --- ESWL treatment protocol --- p.72 / Chapter 4.2.2 --- Outcome Assessment --- p.73 / Chapter 4.2.3 --- Mathematical model development --- p.75 / Chapter 4.2.4 --- Statistical analysis --- p.76 / Chapter 4.3 --- Results --- p.77 / Chapter 4.3.1 --- Baseline characteristics and treatment modalities --- p.78 / Chapter 4.3.2 --- ESWL treatment outcome --- p.79 / Chapter 4.3.3 --- Mathematical model --- p.81 / Chapter 4.4 --- Discussion --- p.82 / Chapter 4.4.1 --- Overall treatment outcome improved by the use of slower rate --- p.82 / Chapter 4.4.2 --- When should we use fast/slow rate? --- p.86 / Chapter 4.4.3 --- Mathematical model to predict ESWL outcome --- p.88 / Chapter 4.5 --- Conclusion --- p.91 / Chapter 5. --- The role of shock wave delivery rate and patient-controlled analgesia in pain --- p.101 / Chapter 5.1 --- Introduction --- p.102 / Chapter 5.2 --- Materials and Methods --- p.104 / Chapter 5.2.1 --- ESWL treatment protocol and PCA settings --- p.104 / Chapter 5.2.2 --- Outcome Assessment --- p.105 / Chapter 5.2.3 --- Statistical analysis --- p.107 / Chapter 5.3 --- Results --- p.108 / Chapter 5.3.1 --- Baseline characteristics and treatment modalities --- p.108 / Chapter 5.3.2 --- Pain experience and satisfaction with PCA at different shock wave delivery rates --- p.108 / Chapter 5.3.3 --- Correlation between rate pain --- p.110 / Chapter 5.3.4 --- Vital signs --- p.110 / Chapter 5.4 --- Discussion --- p.111 / Chapter 5.4.1 --- Adverse complication was mild with PCA using alfentanil --- p.111 / Chapter 5.4.2 --- Less pain experience with 60 SWs/min --- p.112 / Chapter 5.4.3 --- Why PCA usage was the same in both groups? --- p.112 / Chapter 5.4.4 --- No correlation with treatment outcome --- p.114 / Chapter 5.5 --- Conclusion --- p.115 / Chapter 6. --- "The relations among rate of shock wave delivery, induced renal injury and acute complications" --- p.128 / Chapter 6.1 --- Introduction --- p.129 / Chapter 6.2 --- Materials and Methods --- p.130 / Chapter 6.2.1 --- ESWL treatment protocol --- p.130 / Chapter 6.2.2 --- Outcome Assessment --- p.131 / Chapter 6.2.3 --- Statistical analysis --- p.136 / Chapter 6.3 --- Results --- p.137 / Chapter 6.3.1 --- Baseline characteristics and treatment modalities --- p.137 / Chapter 6.3.2 --- Quality control of creatinine and NAG --- p.137 / Chapter 6.3.3 --- Standard curves ofIL-18 and NGAL --- p.137 / Chapter 6.3.4 --- Higher levels of urinary NAG and IL-18 in 60 SWs/min group --- p.138 / Chapter 6.3.5 --- Similar levels of urinary NGAL in both groups --- p.138 / Chapter 6.3.6 --- Unplanned hospital visits were similar in both groups --- p.139 / Chapter 6.4 --- Discussion --- p.140 / Chapter 6.4.1 --- More tubular damages caused by slower rate --- p.140 / Chapter 6.4.2 --- Escalated inflammatory activities in 60 SWs/min --- p.141 / Chapter 6.4.3 --- Vascular damage and ischemic insults were the same in both groups? --- p.142 / Chapter 6.4.4 --- Post-operative complications are similar in both groups --- p.142 / Chapter 6.4.5 --- 60 SWs/min vs. 120 SWs/min - What makes the difference in renal injury? --- p.143 / Chapter 6.5 --- Conclusion --- p.145 / Chapter 7. --- Discussion --- p.154 / Chapter 7.1 --- General discussion --- p.155 / Chapter 8. --- Conclusion --- p.158 / Chapter 8.1 --- General conclusion --- p.159 / Appendix --- p.160 / Appendix I --- p.161 / Appendix II --- p.163 / References --- p.167
9

From Transformation to Therapeutics : Diverse Biological Applications of Shock Waves

Ganadhas, Divya Prakash January 2014 (has links) (PDF)
Chapter–I Introduction Shock waves appear in nature whenever the different elements in a fluid approach one another with a velocity larger than the local speed of sound. Shock waves are essentially non-linear waves that propagate at supersonic speeds. Such disturbances occur in steady transonic or supersonic flows, during explosions, earthquakes, tsunamis, lightening strokes and contact surfaces in laboratory devices. Any sudden release of energy (within few μs) will invariably result in the formation of shock wave since it is one of the efficient mechanisms of energy dissipation observed in nature. The dissipation of mechanical, nuclear, chemical, and electrical energy in a limited space will result in the formation of a shock wave. However, it is possible to generate micro-shock waves in laboratory using different methods including controlled explosions. One of the unique features of shock wave propagation in any medium (solid, liquid or gases) is their ability to instantaneously enhance pressure and temperature of the medium. Shock waves have been successfully used for disintegrating kidney stones, non-invasive angiogenic therapy and osteoporosis treatment. In this study, we have generated a novel method to produce micro-shock waves using micro-explosions. Different biological applications were developed by further exploring the physical properties of shock waves. Chapter – II Bacterial transformation using micro-shock waves In bacteria, uptake of DNA occurs naturally by transformation, transduction and conjugation. The most widely used methods for artificial bacterial transformation are procedures based on CaCl2 treatment and electroporation. In this chapter, controlled micro-shock waves were harnessed to develop a unique bacterial transformation method. The conditions have been optimized for the maximum transformation efficiency in E. coli. The highest transformation efficiency achieved (1 × 10-5 transformants per cell) was at least 10 times greater than the previously reported ultrasound mediated transformation (1 × 10-6 transformants per cell). This method has also been successfully employed for the efficient and reproducible transformation of Pseudomonas aeruginosa and Salmonella Typhimurium. This novel method of transformation has been shown to be as efficient as electroporation with the added advantage of better recovery of cells, economical (40 times cheaper than commercial electroporator) and growth-phase independent transformation. Chapter – III Needle-less vaccine delivery using micro-shock waves Utilizing the instantaneous mechanical impulse generated behind the micro-shock wave during controlled explosion, a novel non-intrusive needleless vaccine delivery system has been developed. It is well established, that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle free devices for epidermal delivery have inherent problems from the perspective of patient safety and comfort. The penetration depth of less than 100 µm in the skin can elicit higher immune response without any pain. Here the efficient utilization of the device for micro-shock wave mediated vaccination was demonstrated. Salmonella enterica serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. The device mediated vaccination elicits better protection as well as IgG response even in lower vaccine dose (ten-fold lesser), compare to other routes of vaccination. Chapter – IV In vitro and in vivo biofilm disruption using shock waves Many of the bacteria secrete highly hydrated framework of extracellular polymer matrix on encountering suitable substrates and get embedded within the matrix to form biofilm. Bacterial colonization in biofilm form is observed in most of the medical devices as well as during infections. Since these bacteria are protected by the polymeric matrix, antibiotic concentration of more than 1000 times of the MIC is required to treat these infections. Active research is being undertaken to develop antibacterial coated medical implants to prevent the formation of biofilm. Here, a novel strategy to treat biofilm colonization in medical devices and infectious conditions by employing shock waves was developed. Micro-shock waves assisted disintegration of Salmonella, Pseudomonas and Staphylococcus biofilm in urinary catheters was demonstrated. The biofilm treated with micro-shock waves became susceptible to antibiotics, whereas the untreated was resistant. Apart from medical devices, the study was extended to Pseudomonas lung infection model in mice. Mice exposed to shock waves responded well to ciprofloxacin while ciprofloxacin alone could not rescue the mice from infection. All the mice survived when antibiotic treatment was provided along with shock wave exposure. These results clearly demonstrate that shock waves can be used along with antibiotic treatment to tackle chronic conditions resulting from biofilm formation in medical devices as well as biological infections. Chapter – V Shock wave responsive drug delivery system for therapeutic application Different systems have been used for more efficient drug delivery as well as targeted delivery. Responsive drug delivery systems have also been developed where different stimuli (pH, temperature, ultrasound etc.) are used to trigger the drug release. In this study, a novel drug delivery system which responds to shock waves was developed. Spermidine and dextran sulfate was used to develop the microcapsules using layer by layer method. Ciprofloxacin was loaded in the capsules and we have used shock waves to release the drug. Only 10% of the drug was released in 24 h at pH 7.4, whereas 20% of the drug was released immediately after the particles were exposed to shock waves. Almost 90% of the drug release was observed when the particles were exposed to shock waves 5 times. Since shock waves can be used to induce angiogenesis and wound healing, Staphylococcus aureus skin infection model was used to show the effectiveness of the delivery system. The results show that shock wave can be used to trigger the drug release and can be used to treat the wound effectively. A brief summary of the studies that does not directly deal with the biological applications of shock waves are included in the Appendix. Different drug delivery systems were developed to check their effect in Salmonella infection as well as cancer. It was shown for the first time that silver nanoparticles interact with serum proteins and hence the antimicrobial properties are affected. In a nutshell, the potential of shock waves was harnessed to develop novel experimental tools/technologies that transcend the traditional boundaries of basic science and engineering.

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