A Micro-Thermal Sensor for Focal Therapy Applications

There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3ω� technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of the pulmonary vein (PV). To begin with “3ω� sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoabalation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode new measurements related to tissue vs. fluid (i.e. water) contact, fluid flow conditions, tissue thickness, and phase change were made. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3ω� sensors on in vivo deployed focal therapy probe surfaces (i.e. balloons or catheters)

Skin-Integrated wearable systems and implantable biosensors: a comprehensive review

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting the current research and development of bio-integrated and implanted biosensors. These devices are micro- and nano-fabricated, according to numerous techniques that are adapted in order to offer a suitable mechanical match of the biosensor to the surrounding tissue, and therefore decrease the body’s biological response. For this, most of the skin-integrated and implanted biosensors use a polymer layer as a versatile and flexible structural support, combined with a functional/active material, to generate, transmit and process the obtained signal. A few challenging issues of implantable biosensor devices, as well as strategies to overcome them, are also discussed in this review, including biological response, power supply, and data communication.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017

은나노와이어/탄성 블록-공중합체의 나노복합체를 이용한 신축성 전극과 의료소자로의 활용

학위논문 (박사)-- 서울대학교 대학원 공과대학 화학생물공학부, 2017. 8. 김대형.Stretchable conductors with high conductivity and stable performance under deformation are potentially highly useful for fabricating improved stretchable and wearable devices. Stretchable conductive nanocomposites comprising a percolation network of various conductive nanomaterials are being vigorously investigated to utilize their outstanding electrical and mechanical properties. Silver nanowire-based stretchable conductor, in particular, showed stable electrical performance under extreme mechanical deformation because of its intrinsically high conductivity and high aspect ratio. This dissertation describes the synthesis of highly conductive and stretchable silver nanowire/elastomer nanocomposite and device fabrication processing to minimize strain, so as to develop stretchable bio-medical devices such as articular thermotherapy device and epicardial mesh for cardiac resynchronizing therapy. First, a soft, thin, and stretchable heater was developed by using a nanocomposite of silver nanowires and a poly(styrene-butadiene-styrene) (SBS) elastomer. A highly conductive and homogeneous nanocomposite was formed by the ligand exchange reaction of silver nanowires. By patterning the nanocomposite with serpentine-mesh structures, conformal lamination of devices on curvilinear joints was achieved, which led to effective heat transfer even during motion. The combination of a homogeneous conductive elastomer, a stretchable design, and a custom-designed electronic band helped create a novel wearable heater system that can be used for long-term and continuous articular thermotherapy. Second, the epicardial device was developed to improve the systolic function in a diseased rat heart without impeding the diastolic function by wrapping the device around the rat heart. The epicardial mesh was designed with elastic properties that are nearly identical to those of the epicardial tissue of the rat heart, and hence, the mesh functioned as a structural component by reducing the host-myocardial wall stress. In addition, the epicardial mesh was able to detect electrical signals reliably on the moving rat heart as well as activate the entire ventricular myocardium simultaneously through synchronized electrical stimulation over the ventricles. Electrically and mechanically optimized epicardial mesh using the ligand-exchanged silver nanowire and SBS nanocomposite improved the hemodynamics in experimental heart failure in the rodent. Finally, a new biocompatible and conductive nanocomposite was developed for stretchable bio-medical devices. As the stretchable conductive composites become widely available as an implantable biomedical device, its biocompatibility must be improved. To overcome the limited biocompatibility of the silver-based nanocomposite, a gold nanoshell was encapsulated on the ultra-long silver nanowire (Ag@AuNW) to prevent the toxic silver ion from leaching out. The formed novel percolation network in the fabricated Ag@AuNW and SBS composite showed stable electrical performance of stretchable conductors under extreme mechanical strain (up to 180%), resulting in high conductivity and stretchabiltiy. A 3D customized cardiac mesh-sock for the porcine heart was fabricated using the Ag@AuNW/SBS composite. In an acute-MI porcine heart, the progress of heart disease was monitored by chronological cardiac activity mapping through a customized 3D mesh sock. Multi-channel electrodes on the epicardial surface diversified the pacing sites on the dysfunctional heart, enabling disease-specific treatment by offering various electrical treatment options without any spatial limitation.Chapter 1. Strategy of fabrication for stretchable conductor and applications in stretchable electronics １ 1.1. Introduction １ 1.2. Nanomaterials, assembly, and device designs for flexible and stretchable electronics ４ 1.3 strategy for stretchable conductor to enhance stretchability ７ 1.4. Applications of stretchable conductor using carbon based material and silver based materials １２ 2.5 Reference ２２ Chapter 2. Stretchable Heater Using Ligand-Exchanged Silver Nanowire Nanocomposite for Wearable Articular Thermotherapy ２６ 2.1 introduction ２６ 2.2 Experimental Section ２８ 2.3 Result and Discussion ３６ 2.4 Conclusion ５７ 2.5 Reference ５８ Chapter 3. Electromechanical cardioplasty using a wrapped soft, highly conductive epicardial mesh. ６３ 3.1 introduction ６３ 3.2 Experimental Section ６６ 3.3 Result and Discussion ６８ 3.4 Conclusion ９１ 3.5 Reference ９２ Chapter 4. Highly conductive and biocompatible stretchable conductor for 3D multi-polar cardiac sock ９５ 4.1 introduction ９５ 4.2 Experimental Section ９７ 4.3 Result and Discussion １０１ 4.4 Conclusion １２０ 4.5 Reference １２１ Bibliography 124 Abstract in Korean 128Docto

Mechanics and applications of stretchable serpentine structures

Stretchable structures have been developed for various applications, including expandable coronary stents, deployable sensor networks and stretchable bio-mimetic and bio-integrated electronics. High-performance, stretchable electronics have to utilize high-quality and long-lasting inorganic electronic materials such as silicon, oxide dielectrics and metals, which are intrinsically stiff and often brittle. It is therefore an interdisciplinary challenge to make inorganic electronics stretchable while retaining their electronic functionality. Patterning stiff materials into serpentine-shaped wavy ribbons has become a popular strategy for fabricating stretchable inorganic electronics. However due to a lack of mechanics understanding, design of serpentine structures is still largely empirical, whether for freestanding or substrate supported serpentines. This dissertation systematically investigates the mechanics of serpentine structures with emphasis on the effects of serpentine geometry and substrate stiffness, which involves theoretical analysis, numerical simulation, and experimental validation. Our theory has successfully predicted the stretchability and stiffness of various serpentine shapes and has been applied to the optimization of serpentine designs under practical constraints. We are also the first to point out that not all geometric effects are monotonic and serpentines are not always more stretchable than linear ribbons. To manufacture high quality serpentine ribbons with high throughput and low cost, we have invented a “cut-and-paste” method to fabricate both metallic and ceramic serpentines. As a demonstration of our method, a noninvasive, tattoo-like multifunctional epidermal sensor system has been built for the measurement of electrophysiological signals, skin temperature, skin hydration, and respiratory rate. Engineering of epidermal stretchable antenna for wireless communication is also detailed and rationalized.Mechanical Engineerin

Laser-assisted processing of multilayer films for inexpensive and flexible biomedical microsystems

Flexible/stretchable electronics offer ideal properties for emerging health monitoring devices that can seamlessly integrate with the soft, curvilinear, and dynamic surfaces of the human body. The resulting capabilities have allowed novel devices for monitoring physiological parameters, improving surgical procedures, and human-machine interfaces. While the attractiveness of these devices are indubitable, their fabrication by conventional cleanroom techniques makes them expensive and incompatible with rapid large-scale (e.g., roll-to-roll) production. The purpose of this research is to develop inexpensive fabrication technologies using low-cost commercial films such as polyimide, paper, and metalized paper that can be utilized for developing various flexible/stretchable physical and chemical sensors for wearable and lab-on-chip applications. The demonstrated techniques focus on an array of laser assisted surfaces modification and micromachining strategies with the two commonly used CO2 and Nd: YAG laser systems. The first section of this dissertation demonstrates the use of localized pulsed CO2 laser irradiation to selectively convert thermoset polymer films (e.g., polyimide) into electrically conductive highly porous carbon micro/nanostructures.Thisprocessprovidesauniqueandfacileapproachfordirect writing of carbonized conductive patterns on flexible polyimide sheets in ambient conditions, eliminating complexities of current methods such as expensive CVD processes and complicated formulation/preparation of conductive carbon based inks used in ink jet printing. The highly porous laser carbonized layer can be transferred to stretchable elastomer or further functionalized with various chemical substances such as ionic solutions, nanoparticles, and chemically conductive polymers to create different mechanical and chemical sensors. The second section of this dissertation describes the use of laser ablation for selective removal of material from multilayer films such as ITO-coated PET, parchment paper, and metalized paper to create disposable diagnostic platforms and in-vitro models for lab-on-chip based studies. The ablated areas were analyzed using electrical, mechanical, and surface analysis tools to understand change in physical structure and chemical properties of the laser ablated films. As proof-of-concept demonstrations of these technologies, four different devices are presented here: mechanical, electrochemical, and environmental sensors along with an in-vitro cell culture platform. All four devices are designed, fabricated, and characterized to highlight the capability of commercial laser processing systems in the production of the next generation, low-cost and flexible biomedical devices

연성 및 생재흡수성 전자소자용 비휘발성 메모리 소자와 집적센서 구현

학위논문 (박사)-- 서울대학교 대학원 : 화학생물공학부, 2015. 8. 김대형.Over years, major advances in healthcare have been made through research in the fields of nanomaterials and microelectronics technologies. However, the mechanical and geometrical constraints inherent in the standard forms of rigid electronics have imposed challanges of unique integration and therapeutic delivery in non-invasive and minimally invasive medical devices. Here, we describe two types of multifunctional electronic systems. The first type is wearable-on-the-skin systems that address the challenges via monolithic integration of nanomembranes fabricated by top-down approach, nanotubes and nanoparticles assembled by bottom-up strategies, and stretchable electronics on tissue-like polymeric substrate. The system consists of physiological sensors, non-volatile memory, logic gates, and drug-release actuators. Some quantitative analyses on the operation of each electronics, mechanics, heat-transfer, and drug-diffusion characteristic validated their system-level multi-functionalities. The second type is a bioresorbable electronic stent with drug-infused functionalized nanoparticles that takes flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and photothermal therapy. In vivo and ex vivo animal experiments as well as in vitro cell researches demonstrate its unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system. As demonstrations of these technologies, we herein highlight two representative examples of multifunctional systems in order of increasing degree of invasiveness: electronically enabled wearable patch and endovascular electronic stent that incorporate onboard physiological monitoring, data storage, and therapy under moist and mechanically rigorous conditions.Contents Abstract Chapter 1. Introduction 1.1 Organic flexible and wearable electronics.................................................. 1 1.2 Inorganic flexible and wearable electronics............................................... 14 1.3 Flexible non-volatile memory devices.......................................................... 25 1.4 Bioresorbable materials and devices........................................................... 34 References Chapter 2. Multifunctional wearable devices for diagnosis and therapy of movement disorders 2.1 Introduction ................................................................................. 45 2.2 Experimental Section ......................................................................... 49 2.3 Result and Discussion ........................................................................ 65 2.4 Conclusion ................................................................................... 95 References Chapter 3. Stretchable Carbon Nanotube Charge-Trap Floating-Gate Memory and Logic Devices for Wearable Electronics 3.1 Introduction ................................................................................ 101 3.2 Experimental Section ........................................................................ 104 3.3 Result and Discussion ....................................................................... 107 3.4 Conclusion .................................................................................. 138 References Chapter 4. Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases 4.1 Introduction ................................................................................ 148 4.2 Experimental Section ........................................................................ 151 4.3 Result and Discussion ....................................................................... 173 4.4 Conclusion .................................................................................. 219 References 국문 초록 (Abstract in Korean) .................................................................. 230Docto

Surgical Instruments based on flexible micro-electronics

This dissertation explores strategies to create micro-scale tools with integrated electronic and mechanical functionalities. Recently developed approaches to control the shape of flexible micro-structures are employed to fabricate micro-electronic instruments that embed components for sensing and actuation, aiming to expand the toolkit of minimally invasive surgery. This thesis proposes two distinct types of devices that might expand the boundaries of modern surgical interventions and enable new bio-medical applications. First, an electronically integrated micro-catheter is developed. Electronic components for sensing and actuation are embedded into the catheter wall through an alternative fabrication paradigm that takes advantage of a self-rolling polymeric thin-film system. With a diameter of only 0.1 mm, the catheter is capable of delivering fluids in a highly targeted fashion, comprises actuated opposing digits for the efficient manipulation of microscopic objects, and a magnetic sensor for navigation. Employing a specially conceived approach for position tracking, navigation with a high resolution below 0.1 mm is achieved. The fundamental functionalities and mechanical properties of this instrument are evaluated in artificial model environments and ex vivo tissues. The second development explores reshapeable micro-electronic devices. These systems integrate conductive polymer actuators and strain or magnetic sensors to adjust their shape through feedback-driven closed loop control and mechanically interact with their environment. Due to their inherent flexibility and integrated sensory capabilities, these devices are well suited to interface with and manipulate sensitive biological tissues, as demonstrated with an ex vivo nerve bundle, and may facilitate new interventions in neural surgery.:List of Abbreviations 1 Introduction 1.1 Motivation 1.2 Objectives and structure of this dissertation 2 Background 2.1 Tools for minimally invasive surgery 2.1.1 Catheters 2.1.2 Tools for robotic micro-surgery 2.1.3 Flexible electronics for smart surgical tools 2.2 Platforms for shapeable electronics 2.2.1 Shapeable polymer composites 2.2.2 Shapeable electronics 2.2.3 Soft actuators and manipulators 2.3 Sensors for position and shape feedback 2.3.1 Magnetic sensors for position and orientation measurements 2.3.2 Strain gauge sensors 3 Materials and Methods 3.1 Materials for shapeable electronics 3.1.1 Metal-organic sacrificial layer 3.1.2 Polyimide as reinforcing material 3.1.3 Swelling hydrogel for self assembly 3.1.4 Polypyrrole for flexible micro actuators 3.2 Device fabrication techniques 3.2.1 Photolithography 3.2.2 Electron beam deposition 3.2.3 Sputter deposition 3.2.4 Atomic layer deposition 3.2.5 Electro-polymerization of polypyrrole 3.3 Device characterization techniques 3.3.1 Kerr magnetometry 3.3.2 Electro-magnetic characterization of sensors 3.3.3 Electro-chemical analysis of polypyrrole 3.3.4 Preparation of model environments and materials 3.4 Sensor signal evaluation and processing 3.4.1 Signal processing 3.4.2 Cross correlation for phase analysis 3.4.3 PID feedback control 4 Electronically Integrated Self Assembled Micro Catheters 4.1 Design and Fabrication 4.1.1 Fabrication and self assembly 4.1.2 Features and design considerations 4.1.3 Electronic and fluidic connections 4.2 Integrated features and functionalities 4.2.1 Fluidic transport 4.2.2 Bending stability 4.2.3 Actuated micro manipulator 4.3 Magnetic position tracking 4.3.1 Integrated magnetic sensor 4.3.2 Position control with sensor feedback 4.3.3 Introduction of magnetic phase encoded tracking 4.3.4 Experimental realization 4.3.5 Simultaneous magnetic and ultrasound tracking 4.3.6 Discussion, limitations, and perspectives 5 Reshapeable Micro Electronic Devices 5.1 Design and fabrication 5.1.1 Estimation of optimal fabrication parameters 5.1.2 Device Fabrication 5.1.3 Control electronics and software 5.2 Performance of Actuators 5.2.1 Blocking force, speed, and durability 5.2.2 Curvature 5.3 Orientation control with magnetic sensors 5.3.1 Magnetic sensors on actuated device 5.3.2 Reference magnetic field 5.3.3 Feedback control 5.4 Shape control with integrated strain sensors 5.4.1 Strain gauge curvature sensors 5.4.2 Feedback control 5.4.3 Obstacle detection 5.5 Heterogenous integration with active electronics 5.5.1 Fabrication and properties of active matrices 5.5.2 Fabrication and operation of PPy actuators 5.5.3 Site selective actuation 6 Discussion and Outlook 6.1 Integrated self assembled catheters 6.1.1 Outlook 6.2 Reshapeable micro electronic devices 6.2.1 Outlook 7 Conclusion Appendix A1 Processing parameters for polymer stack layers A2 Derivation of magnetic phase profile in 3D Bibliography List of Figures and Tables Acknowledgements Theses List of Publication

Design of ultra-stretchable nanomesh structures

Wide-ranging applications of integrated stretchable electronics, including sensors, actuators,energy harvesting, etc., are made possible by expeditious advancements in design and mate- rials. Nanomesh structures brought a significant development in this field showing excellent transparency, lower stiffness, and high stretchability. This thesis studies the mechanical properties of hexagonal nanomesh structures made of arc-shaped serpentine traces. Theo- retical and finite element models are developed to investigate the displacement, maximum strain, axial stiffness, stretching rigidity, effective modulus, and stretchability of the hexag- onal nanomesh structures for different thicknesses and arc-angles of the traces. The findings of the analytical process appear to be matched very well with the finite element analysis results. As a result, these verified theoretical formulations can be used to have practical instructions for constructing the nanomesh structures to achieve very higher stretchability and mechanical qualities, which are highly desirable properties in manufacturing wearable electronics and bio-mimetic structures