Biomedical instruments design and development focused on ultrasound, fluorescence, and photoacoustic imaging-guided therapeutic modalities.
- Abstract
- This thesis concept comes from the perception of giving appropriate diagnosis and therapy for the right patient through promising studies in animal models. Different therapy models need to scheme for effectively treating particular situations of diseases. In this current study, three different portable, lightweight, easy-to-use biomedical instruments were designed and applied for different cancer diagnoses and treatments in the laboratory environment.
A lab-based fluorescence imaging system was also fabricated with four different channels corresponding to various fluorescence dyes. The customized control interface integrated with the image processing algorithm allows the boundary and concentration of the contrast agents to be simply quantified. Additionally, photoacoustic imaging (PA) system was developed with high spatial resolution, sufficient scanning range, and speed, compatible with numerous exogenous contrast as well. Using a 532-nm laser source and 625-nm high-pass filter enables us to monitor blood vessels and PA contrast agents separately. Various nanomaterials were developed and combined with the proposed diagnostics devices to generate powerful cancer therapy.
In the very first chapter, the chitosan-polypyrrole nanoparticle was synthesized as an effective dual-modal fluorescence/photoacoustic imaging-guide photothermal contrast agent. Next, the cobalt metal was doped with the hydroxyapatite to develop a fluorescence conjugated nanostructure for drug delivery application. For the third part, the hydroxyapatite nanomaterials were dual-doped with rare earth elements – Ytterbium and Gadolinium. The developed nanoparticles were thus conjugated with the folic acid and IR783 to act as a cancer-targeted contrast agent for photodynamic therapy application.
In the final section, the high-intensity focused ultrasound (HIFU) circuit was constructed to regulate the commercial HIFU transducer. The next step is creating the controller based on the fuzzy logic and the neural network to manipulate the heat generation. The suggested algorithms help to inspect and precisely control the treated sample temperature in real-time. The integration of the HIFU technique and PA imaging was demonstrated as a feasible tool for ex vivo cancer therapy.
Throughout the whole study, the individually proposed therapeutic modalities were planned and feasibly confirmed in different cancer treatment circumstances.
- Issued Date
- 2022
- Awarded Date
- 2022. 8
- Type
- Dissertation
- Publisher
- 부경대학교
- Affiliation
- Pukyong National University, Graduate School
- Department
- 대학원 4차산업융합바이오닉스공학과
- Advisor
- Prof. Junghwan Oh
- Table Of Contents
- Chapter 1 Introduction 1
1.1. Motivation 1
1.2. Objectives and organization of the thesis 1
Chapter 2 Fluorescence/photoacoustic imaging‑guided nanomaterials for highly efficient cancer theragnostic agent 3
2.1. Introduction 3
2.2. Results and Discussion 7
2.2.1 Characterization of CS-PPy NCs and IR-CS-PPy NCs 7
2.2.2 Photothermal performance of IR-CS-PPy NCs 12
2.2.3 In vitro cell cytotoxicity assay and photothermal therapy 14
2.2.4 Fluorescence imaging and performance test 16
2.2.5 Photoacoustic imaging and performance test 20
2.2.6 In vivo photothermal therapy 23
2.3. Conclusion 26
2.4. Materials and Methods 27
2.4.1 Synthesis of CS-PPy NCs and IR-CS-PPy NCs 27
2.4.2 Characterization of synthesized CS-PPy NCs and IR-CS-PPy NCs 27
2.4.3 In vitro cell culture study 28
2.4.4 The animal model 28
2.4.5 Fluorescence imaging system design (LUX 3.0) 29
2.4.6 Photoacoustic imaging system design 31
2.4.7 Fluorescence imaging 33
2.4.8 Photoacoustic imaging 34
2.4.9 Measurement of the photothermal performance of IR-CS-PPy NCs 34
2.4.10 In vitro cytotoxicity assay and photothermal efficiency 35
2.4.11 In vivo photothermal therapy 36
2.4.12 Histological analysis 37
2.4.13 Statistical analysis 37
2.5. References 37
Chapter 3 Fluorescence conjugated nanostructured cobalt-doped hydroxyapatite platform for imaging-guided drug delivery application 46
3.1. Introduction 46
3.2. Materials and Methods 49
3.2.1 Synthesis of Co-doped HAp nanoparticles 49
3.2.2 Characterization 50
3.2.3 Biocompatibility of synthesized nanoparticles 51
3.2.4 Lab-made indigenous fluorescence system (LUX 4.0) 52
3.2.5 In vitro fluorescence imaging 52
3.2.6 Doxorubicin (DOX)-loading on HAp and Co-HAp (Co: 0.5, 1.0, 2.0 mol%) nanoparticles 53
3.2.7 Doxorubicin releasing kinetics at different pH for 2.0 mol% Co-Hap nanoparticles 53
3.3. Results 54
3.3.1 Characterization 54
3.3.2 Biocompatibility of synthesized nanoparticles 63
3.3.3 In vitro fluorescence imaging 65
3.3.4 Kinetics of DOX-loading and releasing 68
3.4. Conclusion 69
3.5. References 70
Chapter 4 Yetteribium-Gadolinium co-doped hydroxyapatite as a potential contrast agent for bio-imaging and biomedical applications 76
4.1. Introduction 76
4.2. Materials and Methods 79
4.2.1 Synthesis of Yb3+ and Gd3+ dual-doped HAp nanoparticles 79
4.2.2 Characterization 80
4.2.3 Biological study 81
4.2.4 Animal model 82
4.2.5 Fluorescence imaging 83
4.2.6 Photodynamic efficiency (ROS study) 84
4.2.7 In vitro photodynamic therapy 84
4.3. Results and Discussion 85
4.3.1 Characterization 85
4.3.2 Biocompatibility of synthesized nanoparticles 92
4.3.3 Fluorescence imaging 94
4.3.4 Photodynamic efficiency (ROS study) 97
4.3.5 In vitro photodynamic efficiency 99
4.4. Conclusion 100
4.5. Reference 101
Chapter 5 Fuzzy Logic Control-Based HIFU System Integrated with Photoacoustic Imaging Module for Ex Vivo Artificial Tumor Treatment 107
5.1. Introduction 107
5.2. Materials and Methods 109
5.2.1 Electrical Design of HIFU System 109
5.2.2 Characterization of HIFU System 114
5.2.3 Ex Vivo Experiment with Fuzzy Logic Control 116
5.2.4 Ex Vivo Experiment with PAI System 118
5.2.5 Statistical Analysis 121
5.3. Results 121
5.3.1 Characteristic of HIFU System 121
5.3.2 Ex Vivo Experiment Results Using Fuzzy Logic Control 123
5.3.3 Ex Vivo HIFU Therapy Integrated with PAI System for the Artificial Breast Tumor Treatment 126
5.4. Discussion 127
5.5. Conclusion 131
5.6. References 131
Chapter 6 Deep neural network design for HIFU thermal control in ex vivo experiment 139
6.1. Introduction 139
6.2. Materials and Methods 140
6.2.1 Schematic diagram and experimental setup 140
6.2.2 HIFU control and temperature prediction 141
6.2.3 The control system 144
6.3. Results and Discussion 145
6.3.1 Network training 145
6.3.2 HIFU thermal control 146
6.4. Conclusion 147
6.5. References 148
Chapter 7 Conclusions 150
Publications 151
- Degree
- Doctor
- Appears in Collections:
- 대학원 > 4차산업융합바이오닉스공학과
- Files in This Item:
-
-
Download
Biomedical instruments design and development focused on ultrasound, fluorescence, and photoacoustic.pdf
기타 데이터 / 6.74 MB / Adobe PDF
-
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.