Design and Simplified Fabrication of a Cyclic Olefin Copolymer-based Integrated Electrode-Chip System for Retinal Prosthesis = 인공망막 장치를 위한 Cyclic Olefin Copolymer 기반의 전극-칩 통합 시스템의 공정법 개발 및 설계

다국어 초록 (Multilingual Abstract)

Retinal prostheses aim to restore partial vision in patients suffering from photoreceptor degeneration by electrically stimulating the remaining retinal neurons. Despite remarkable progress in recent decades, existing devices remain constrained by limited long-term reliability, insufficient stimulation selectivity, and complex packaging architectures that hinder miniaturization and chronic implantation. These limitations have resulted in highly restricted visual restoration, while long-term implantation has often led to issues such as electrode delamination and inflammatory responses. In particular, the use of heterogeneous materials and multi-step assembly processes introduces mechanically and chemically vulnerable interfaces, often leading to moisture ingress, electrode delamination, and premature device failure. Therefore, ensuring long-term stability, efficient neural stimulation, and spatially compact integration has become a critical design objective for next-generation retinal prostheses. Reliability in retinal prostheses should thus be addressed not only through material performance, but also through fabrication simplicity and structural integration.

This dissertation proposes a monolithic polymer-based design framework that integrates material selection, structural optimization, and system-level packaging through fabrication-level unification within a single thermoplastic material platform. Cyclic olefin copolymer (COC) was selected as the core material due to its exceptionally low water permeability, chemical inertness, optical transparency, and established biocompatibility. These properties suggest that COC has strong potential as a substrate material for retinal prostheses by addressing key limitations of conventional polymers, particularly in terms of long-term encapsulation stability and chemical durability. However, previously reported COC-based neural electrodes have not fully exploited this potential and have often suffered from insufficient mechanical compliance and interfacial instability, primarily due to residual stress induced during fabrication and poor metal adhesion on the inherently hydrophobic COC surface.

To overcome these challenges, this study first focused on establishing a fabrication strategy that could unlock the intrinsic advantages of COC. Thermoforming and annealing processes were systematically optimized to enhance flexibility and relieve residual stress, while plasma surface modification was employed to improve interfacial reliability between metals and the polymer substrate. Based on these process optimizations, COC-based planar electrode arrays were subsequently developed as a reliable baseline structure for long-term insulation and mechanical durability.

The resulting planar electrodes exhibited significantly improved mechanical robustness and interfacial stability compared to previously reported COC-based designs. Accelerated soaking and cyclic bending tests verified stable encapsulation performance over extended operation, and in ex vivo retinal stimulation experiments, the fabricated electrodes effectively transmitted electrical signals to retinal tissue, demonstrating stable and reproducible responses.

To improve stimulation selectivity beyond planar configurations, a three-dimensional plateau electrode geometry was subsequently introduced by exploiting the thermoformability of COC. The plateau structure locally elevates electrode sites to reduce the electrode–cell distance while maintaining smooth, rounded surface profiles. This geometry suppresses lateral current spreading without relying on sharp or invasive features commonly found in conventional three-dimensional electrodes, thereby addressing reported limitations of needle-, pillar-, or spike-type structures. Importantly, the plateau electrodes were fabricated through a simple thermoforming-based process without introducing additional materials or complex patterning steps. Finite element simulations and electrochemical analyses confirmed enhanced electric field confinement and improved charge transfer efficiency compared to planar electrodes fabricated from the same material.

Furthermore, an inverse truncated pyramid (ITP) structure was designed and implemented, embedding the stimulation chip within the COC substrate and directly connecting it to the metal layer on the same level as the electrode pattern. This structure enables semiconductor chips to be embedded directly within the polymer substrate and electrically integrated without wire bonding. By eliminating bulky housings and heterogeneous encapsulation layers, the proposed packaging approach significantly reduces dead space and assembly complexity. This configuration minimized total thickness and enabled a thin and flexible packaging structure through thermoforming. Finite element analysis validated the structural efficiency, and the integration process was experimentally verified using embedded phototransistors, confirming that chip embedding and electrode integration did not compromise device performance.

In conclusion, this dissertation demonstrates that fabrication simplicity achieved through monolithic integration is a key enabler of long-term reliability in retinal prostheses. By unifying material selection, electrode geometry, and chip packaging within a single thermoplastic polymer platform, the proposed framework simultaneously improves encapsulation durability, stimulation selectivity, and packaging scalability. Beyond retinal prostheses, this approach provides general design principles for future implantable neural interfaces that require compact form factors, mechanical robustness, and stable long-term operation in biological environments.

국문 초록 (Abstract)

인공망막(retinal prosthesis)은 광수용체 변성으로 인한 실명 환자의 잔존 시신경세포를 전기적으로 자극하여 부분적인 시각을 회복시키는 것을 목표로 한다. 지금까지 많은 기술적 발전이 이루어졌지만, 기존의 인공망막은 구조적 신뢰성 부족, 낮은 자극 효율, 그리고 칩과 전극을 안정적으로 통합하기 어려운 설계 제약으로 인해 어려움을 겪고 있다. 이러한 한계로 인해 실제 시각 회복 수준은 매우 제한적이며, 장기 사용 시 전극 박리나 염증 반응 등 부작용 사례도 반복적으로 보고되어 왔다. 따라서 인공망막 설계 시 장기간 안정성을 유지하면서도 효율적인 신경 자극과 공간 효율적인 집적을 동시에 달성하는 것이 중요한 과제로 대두되고 있다.

본 연구는 이러한 한계를 해결하기 위해 재료 선택부터 구조 설계, 시스템 패키징에 이르는 전 과정을 통합적으로 고려한 폴리머 기반 설계 프레임워크를 제안한다. 주재료로 선택된 COC(cyclic olefin copolymer)는 낮은 수분 투과율, 높은 화학적 안정성, 그리고 우수한 생체적합성을 지닌다. 더 나아가 COC는 전극 형성, 구조적 성형, 칩 패키징을 단일 열가소성 폴리머 플랫폼 내에서 구현할 수 있는 공정 전략을 가능하게 한다. 이러한 특성은 장기 삽입 환경에서는 큰 장점이지만, 소수성 표면 특성으로 인해 다른 재료와의 접착 및 계면 형성이 어렵다는 단점도 존재한다. 이에 본 연구에서는 열성형 조건과 어닐링 공정을 최적화하여 기판의 유연성과 잔류 응력을 완화하고, 플라즈마 처리 및 표면 개질을 통해 금속과 폴리머 간의 계면 접합 신뢰성을 확보하였다. 그 결과, COC의 안정성과 유연성이 동시에 확보된 상태에서 공정 적합성과 구조적 신뢰성이 우수한 전극–칩 통합 구조가 구현되었다.

이러한 기반 위에서 장기 절연성과 기계적 안정성을 확보하기 위한 평면 전극 어레이를 제작되었으며, 가속침지실험 및 반복 굽힘 시험을 통해 장기 안정성 및 기계적 내구성이 검증되었다. 또한, ex vivo 환경에서 망막 자극 실험을 수행한 결과, 제작된 전극이 망막 조직에 전기 신호를 안정적으로 전달하며 일관된 반응을 유도하는 것이 확인되었다. 여기에 더해, 전극–세포 간 접촉을 강화하고 전류 확산을 줄여 자극 효율을 높이기 위해 전극부가 미세하게 돌출된 플라토 (plateau) 구조가 설계되었다. 이를 통해 전기장 집중 효과와 전하 전달 능력이 향상되었으며, 전극–세포 간 상호작용이 강화되어 자극 효율이 개선됨이 시뮬레이션 및 전기화학적 분석을 통해 확인되었다. 마지막으로, 자극 칩을 COC 기판 내부에 삽입하고 전극 패턴과 동일한 레벨에서 금속층으로 직접 연결하는 새로운 ITP (inverse truncated pyramid) 구조가 설계 및 구현되었다. 이 구조는 칩과 전극 간의 전기적 연결을 단일 평면 상에서 형성함으로써 전체 두께를 최소화하고, 열성형 공정을 통해 얇고 유연한 패키징 형태를 실현하였다. 구조적 효율성은 제작 전 유한요소 해석을 통해 검증되었으며, 제작된 시편에서는 광트랜지스터를 삽입하여 통합 및 패키징 공정이 소자 특성에 미치는 영향을 평가하였다. 이를 통해 칩 삽입과 전극 일체형 패키징이 기능적 손상 없이 안정적으로 구현 가능함이 확인되었다.

결론적으로, 본 논문은 유연 폴리머 기반 신경 인터페이스의 새로운 통합 설계 방향을 제시한다. 인캡슐레이션 내구성, 자극 정밀도, 패키징 효율성을 동시에 향상시킴으로써, 생체 환경에서 전기적·기계적 안정성을 장기간 유지할 수 있는 차세대 인공망막 시스템의 기술적 기반을 마련하였다. 이러한 접근은 인공망막의 구조적·기능적 완성도를 높였을 뿐 아니라, 향후 단일 재료 기반의, 두께를 최소화한 유연·고신뢰성 생체전자 시스템 개발에도 실질적인 설계적 통찰을 제공한다.

목차 (Table of Contents)

• 1 Introduction 1
• 1.1 Neural System 1
• 1.2 The Human Visual System 3
• 1.2.1 Retinal Function and Structure 3
• 1.2.2 Retinal Signal Encoding 5
• 1.2.3 Retinal Degeneration and Visual Loss 6
• 1.3 Retinal Prostheses 7
• 1.3.1 Principles of Neural Stimulation 7
• 1.3.1.1 Neuronal Excitability and Threshold 7
• 1.3.1.2 Electrode-Tissue Interface and Electrochemistry 8
• 1.3.1.3 Safe Stimulation Strategies 10
• 1.3.2 Visual Impairment and Rationale for Retinal Prostheses 11
• 1.3.3 System Architecture 12
• 1.3.3.1 Components of Retinal Prosthesis 12
• 1.3.3.2 Classification by Implant Location 14
• 1.3.4 Representative Devices and Achievements 16
• 1.3.5 Limitations and Failure Cases 17
• 1.4 Design Considerations for Retinal Prostheses 20
• 1.4.1 Long-term Stability and Biocompatibility 20
• 1.4.1.1 Desirable Properties 20
• 1.4.1.2 Limitations of Existing Polymers 21
• 1.4.1.3 Cyclic Olefin Copolymer (COC) 22
• 1.4.2 Stimulation Efficiency 24
• 1.4.2.1 Resolution Constraints 24
• 1.4.2.2 Strategies to Overcome Crosstalk 26
• 1.4.3 Chip Embedding and Integration for Intraocular Implants 28
• 1.4.3.1 Conventional Chip Embedding Method 29
• 1.4.3.2 Hermetic Packaging and Emerging Alternatives 30
• 1.5 Motivation and Research Objectives 33
• 1.5.1 Design Requirements for Subretinal Prostheses 33
• 1.5.2 Research Goal and Approach 34
• 2 Methods 40
• 2.1 Planar Electrode Array 40
• 2.1.1 Electrode Fabrication 40
• 2.1.1.1 Substrate Preparation 40
• 2.1.1.2 Surface Modification of COC substrate 44
• 2.1.1.3 Photolithography for Electrode Patterning 45
• 2.1.1.4 Thermal Lamination and Site Opening 47
• 2.1.1.5 Iridium Oxide Plating 47
• 2.1.2 Evaluation of Planar Electrode 50
• 2.1.2.1 Thermal Expansion Analysis 50
• 2.1.2.2 Electrochemical Performance Evaluation 51
• 2.1.2.3 Long-term Reliability Evaluation 51
• 2.1.2.4 Mechanical Durability Evaluation 53
• 2.1.2.5 Exvivo Functional Validation 54
• 2.2 Plateau Electrode Array 56
• 2.2.1 Design Rationale 56
• 2.2.1.1 Tissue–Electrode Interface 56
• 2.2.1.2 Crosstalk Suppression Strategies 57
• 2.2.1.3 Proposed Plateau Geometry 58
• 2.2.1.4 Height Optimization via Simulation 58
• 2.2.2 Electrode Fabrication 60
• 2.2.2.1 Metal Patterning 60
• 2.2.2.2 Thermoforming Mold Design 61
• 2.2.2.3 3D Structure Formation and Encapsulation 63
• 2.2.3 Preliminary Evaluation 64
• 2.2.3.1 Basic Impedance Assessment 64
• 2.3 Chip Integration and Packaging 65
• 2.3.1 Novel Design: Inverse Truncated Pyramid Structure 65
• 2.3.2 Integration Process 66
• 2.3.2.1 Cavity Formation and Chip Embedding 66
• 2.3.2.2 Chip-Substrate Integration 68
• 2.3.2.3 Encapsulation via Lamination 70
• 2.3.3 Evaluation of the ITP-based Chip Integration 70
• 2.3.3.1 Simulation-based Evaluation 70
• 2.3.3.2 Connection Yield Evaluation 71
• 2.3.3.3 Physical Characteristic Evaluation 73
• 2.3.3.4 Temperature Cycling Test 75
• 2.3.3.5 Long-term Reliability 76
• 2.3.3.6 Functional Evaluation After Packaging 76
• 3 Results 79
• 3.1 Planar Electrode Array 79
• 3.1.1 Mechanical Characterization of T-Die-Casted COC Films 79
• 3.1.2 Electrode Fabrication Results 81
• 3.1.2.1 Optimization of Surface Modification 81
• 3.1.2.2 Electrode Layer and Site Opening 84
• 3.1.2.3 Metal Layer Profile 85
• 3.1.3 Electrode Evaluation Results 86
• 3.1.3.1 Thermal Expansion Analysis 86
• 3.1.3.2 Electrochemical Performance Evaluation 87
• 3.1.3.3 Long-term Reliability Evaluation 90
• 3.1.3.4 Mechanical Durability Evaluation 92
• 3.1.3.5 Ex vivo Functional Validation 95
• 3.2 Plateau Electrode Array 97
• 3.2.1 Analysis of Electric Field Confinement 97
• 3.2.2 Structural Observation of the Fabricated Plateau Electrodes 100
• 3.2.3 Electrochemical Performance Evaluation 104
• 3.3 Chip Packaging and Integration 107
• 3.3.1 Simulation-Based Evaluation of the ITP Structure 107
• 3.3.1.1 Structural Stress Distribution 107
• 3.3.1.2 Thermal Dissipation Analysis 109
• 3.3.2 Fabrication and Optimization 111
• 3.3.2.1 Fabrication Results 111
• 3.3.3 Evaluation of Electrical Interconnect Reliability 113
• 3.3.3.1 Resistance Distribution 113
• 3.3.3.2 Connectivity Yield Evaluation 114
• 3.3.4 Reliability Evaluation of the ITP structure 116
• 3.3.4.1 Long-term Reliability Evaluation 116
• 3.3.4.2 Physical Reliability Evaluation 117
• 3.3.4.3 Thermal Reliability Evaluation 119
• 3.3.5 Impact of Packaging on Chip Performance 122
• 4 Discussion 124
• 4.1 Mechanical Behavior Analysis of COC 124
• 4.1.1 Discussion on COC Cracking Behavior 124
• 4.1.2 Thermo–mechanical Stress Analysis 126
• 4.2 Mechanical Reliability Assessment of the ITP Structure 129
• 4.2.1 Structural Failure Mechanism Analysis 130
• 4.2.2 FEA-Based Evaluation of Strain Distribution 132
• 4.3 Process Optimization and Fabrication Refinement 135
• 4.3.1 Considerations on the Site Opening Process 135
• 4.3.2 Lithography Process Optimization for Plateau Electrodes 137
• 4.3.3 PEDOT:PSS Reinforcement of Electrical Interconnects 140
• 4.3.3.1 Material Selection 140
• 4.3.3.2 Preliminary Observation on Lift-off Stability 141
• 4.3.3.3 Coating Process Optimization 142
• 4.4 Discussion on Experimental Findings 144
• 4.4.1 Challenges in Reliable Ex Vivo Evaluation 144
• 4.4.2 Interpretation of Leakage Behavior in the ITP Structure 146
• 5 Conclusion 148
• 6 FutureWorks 151
• 6.1 Prospective in vivo Evaluation 151
• 6.2 Comparative Evaluation of Plateau Electrode Arrays 151
• 6.2.1 Comparative Cell Adhesion Test 152
• 6.2.2 Multi-site Electrochemical Evaluation 153
• 6.3 Expanding into Double-Layer Design 154
• 6.4 Hybrid Polymer Integration for Bending Flexibility 155