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A Study on Soft Bioelectronic Devices for Personalized Healthcare : Materials, Strategies, and Applications

초록/요약

As life expectancy has increased along with the improvement of quality of life worldwide, the interests and demands for individualized healthcare have risen significantly. The recent progress in material, electronic, and IT technology enables the development of various customized wearable and implantable biomedical devices for accurate diagnosis and treatment of individual diseases. In particular, soft bioelectronic devices based on flexible/stretchable materials are attracting great attention due to their advantages of matching mechanical properties with the soft tissue of our body, and show great potential as a personalized biomedical device for the future. In this thesis, we introduce novel soft bioelectronic devices for personalized healthcare developed via an intelligent approach to materials, strategies, and applications that enables improvements in conventional wearable/implantable medical systems. In the first study, we developed highly conductive and biocompatible flexible sensing materials by mixing soft elastomers with similar mechanical properties of human skin and highly conductive nanofillers such as carbon nanotubes (CNTs) and silver nanowires (AgNWs) to develop wearable devices that can be useful in bio-signal monitoring. Such sensing materials were applied on personal belongings such as earphones and eyeglasses, providing simple, comfortable, and unobtrusive wearing with user-friendly design. We demonstrated capable of a human-machine interface (HMI) such as game control along with ubiquitous healthcare through continuous and multiple monitoring of brain waves, eye waves, UV intensity, and motion with personalized soft bioelectronic devices such as earphones and eyeglasses. Next step, we developed an implantable soft bioelectronic device for personalized disease diagnosis and treatment accurately. The developed flexible and stretchable elastomer-based web-like bioelectronic devices can reliably apply to the bladder that can expand volume by about 300 %, enabling diagnosis and treatment of bladder diseases that are difficult to urinate. The multi-sensors (strain gauge, electromyography (EMG) electrodes, temperature meter) integrated into the soft bioelectronic device named ‘electronic web’ continuously monitor the bladder, and the 470nm of micro-led array induces urination of mice via optical stimulation at optimal time depending on the bladder condition through the optogenetic technology. As a further step, we proposed a surgery-free implantable soft bioelectronic device, a promising personalized implantable medical system that does not require surgical intervention to insert into the human body. This surgery-free implantable medical device (SIM) can be folded like a ball and injected into the body through a syringe, and then restored to its original shape via shape recovery functions, enabling correct medical functions after implantation. The bioresorbable SIM that consists of biodegradable materials disappears via bioabsorption without secondary removal surgery after completing the medical functions. In vivo experiments using rodent models demonstrated the proposed medical functions of the SIM and showed significant potential for future personalized medical applications along with non-surgery advantages such as fast healing, fewer inflammations. We believe that the research introduced in this paper will bring widespread interest and have a strong impact on the next-generation personalized healthcare field through the fabrication of soft bioelectronic devices and systems using various flexible/stretchable materials and their practical applications. Novel approaches to various diagnostic and treatment methods presented in this thesis will provide new insights and inspired guides to the healthcare fields for the public.

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목차

Abstract I
Figure List IX
Table List XIV

Chapter 1. Introduction 1

1-1. Soft bioelectronic devices for personalized healthcare 1
1-2. Materials and design strategies for wearable/implantable soft bioelectronic devices 3
1-3. Chapter overview 6

Chapter 2. Flexible conductive composite integrated with personal belongings for wearable healthcare systems, and their applications 7

2-1. Introduction 7

2-2. Wearable In-ear EEG earphone for simple, wireless and real-time EEG monitoring 10
2-2-1. Experiments 10

2-2-1-1. Fabrication of AgNWs/CNTs/PDMS 10
2-2-1-2. Fabrication of an EEG earphone 12
2-2-1-3. EEG experiments and measurements 12

2-2-2. Results and discussion 14
2-2-2-1. In-ear EEG earphone 14
2-2-2-2. Electrical and mechanical characterization of the AgNWs/CNTs/PDMS as an electrode material 16
2-2-2-3. Optimization of electrodes position for EEG measurement in ear 22
2-2-2-4. Evaluation for feasibility of EEG measurement with EEG earphone 24
2-2-2-5. Drowsiness detection 27

2-3. Multi-functional smart electronic eyeglasses (E-glasses) for wearable healthcare system and human-machine interfaces 29

2-3-1. Experiments 30
2-3-1-1. Soft, conductive electrodes based on CNTs/PDMS composites 30
2-3-1-2. Design and fabrication of smart electronic eyeglasses 30
2-3-1-3. Ion gels-based electrochromic materials for color-adjustable lenses 31
2-3-1-4. Experiments on electrophysiological signals 32

2-3-2. Results and discussion 33
2-3-2-1. Smart electronic-glasses (E-glasses) 33
2-3-2-2. Electrical and mechanical characterization of the sensing materials 37
2-3-2-3. Various functional operations through embedded components in the E-glasses. 43
2-3-2-4. Electrical activities of the brain and their applications 47
2-3-2-5. E-glasses for an EOG monitor and human-computer interface 50

2-4. Conclusion 53

Chapter 3. Expandable and implantable bioelectronic device for personalized disease diagnosis and treatment 54

3-1. Introduction 54

3-2. Experiments 57
3-2-1. Fabrication of a soft, expandable electronic complex 57
3-2-2. In vitro experiments of an expandable electronic system using an artificial bladder model 60
3-2-3. Diabetic bladder dysfunction (DBD) models 60
3-2-4. Adeno associated viral constructs, and animal transfection 61
3-2-5. In vivo animal experiments 61
3-2-6. Customized algorithm for regulation of optogenetic stimulation 62

3-3. Results and discussion 65
3-3-1. Overview of the expandable and implantable bioelectronic complex 65
3-3-2. Optical and electrical characterization of the E-thread 69
3-3-3. Theoretical and experimental studies of the mechanical influences of the electronic complex 75
3-3-4. Evaluation of the electronic complex in the mouse disease model 84

3-4. Conclusion 92

Chapter 4. Surgery-free implantable and bioresorbable medical platform 93

4-1. Introduction 93

4-2. Experiments 95
4-2-1. Synthesis of DNA hydrogel 95
4-2-2. Fabrication of a bioresorbable electronic device for surgery-free implantable medical device (SIM) 97
4-2-3. Integration of DNA hydrogel and electronic medical device for complete SIM 99
4-2-4. Preparation of bioresorbable DOX/SIM for wireless and on-demand drug delivery 100
4-2-5. Syringe-assisted implantation of the SIM 101
4-2-6. Evaluation of injection yield of the SIM 101
4-2-7. In vivo demonstration of surgery-free implantation and on-demand wireless thermal actuation provided by DOX/SIM 103

4-3. Results and discussion 104
4-3-1. Surgery-free implantation strategy and demonstration platform of SIM 104
4-3-2. Strategies for materials, structures, and ejection properties for stable implantation of the bioresorbable SIM 109
4-3-3. Mechanical and functional reliability evaluation of the thin, stretchable, fully bioresorbable electronic medical device 124
4-3-4. In-vivo demonstration of the SIM as a wireless, biodegradable, and on-demand drug-delivery system 131

4-4. Conclusion 144


Chapter 5. Conclusion 146

Chapter 6. Bibliography 150

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