(A) study on stretchable microfluidic-integrated biosensor patch for wearable point-of-care testing

다국어 초록 (Multilingual Abstract)

As the demand for personalized preventive medicine through smart healthcare has exploded, the development of wearable POCT system which can continuously monitor personal physiological information such as respiration, heart rate, skin temperature, body motion, and bio-markers in biofluid, and diagnose the personal health status in real-time, is highly required. Among the various components of wearable POCT system, wearable biosensor recently has received tremendous attention as they can continuously and directly detect biomarkers in biofluid, which is closely related to health status. However, there are still several problems such as insufficient stretchability, poor detection accuracy, dependence on detection environment, and biofluid mixing effect, to be solved for implementation of perfect non-invasive and real-time continuous detection.
The stretchability of wearable biosensor is very important not only for preventing noise signal generated by body movements, but also for conformal attachment of wearable biosensor with body to continuously collect biofluid. Therefore, to impart stretchability to non-stretchable materials which are essential for the implementation of high-performance wearable biosensor, the biosensors are directly fabricated on the mogul-patterned substrate which has three-dimensional micro-pattern with continuously connected bumps and valleys in three directions, effectively absorbing the stress generated during physical deformation. In addition, the nanomaterials which have high surface to volume ratio and great chemical stability, is used as catalyst instead of bioreceptor to enhance the detection accuracy and stability against to interfering molecules and detection environment respectively. As a result, stretchable electrochemical and fuel cell-based glucose biosensors with catalytic nanomaterials, which is fabricated on mogul-patterned substrate show high sensitivity to glucose, high selectivity against to interfering molecules, great multi-directional stretchability, and low dependance on detection environments such as pH and temperature.
Furthermore, to prevent the biofluid mixing effect due to the continuous extraction from the body, stretchable cotton materials which is inexpensive, durable, biocompatible, and has great fluid absorption capability even under its stretched condition, based microfluidic devices are developed. The fabricated stretchable cotton materials based microfluidic devices show excellent fluid handling characteristics with constant and stable efficiency even under the various physical deformations. Then, fully stretchable microfluidic-integrated biosensor patches are developed by assembling the stretchable biosensors with stretchable microfluidic device. The fabricated fully stretchable microfluidic-integrated biosensor patches achieve high detection accuracy and reliability through precisely collect and handle the sweat, effectively preventing biofluid mixing effect. Finally, daily sweat glucose level monitoring is perfectly conducted through real-time continuous on-body detection with a fully stretchable biosensor patches attached onto the skin.
In conclusion, the results of this study will open up new horizons of wearable biosensor platforms for personalized preventive medicine by addressing the currently existing limitations in real-time continuous on-body detection.

국문 초록 (Abstract)

스마트 헬스케어를 통한 맞춤형 예방의학에 대한 수요가 폭발적으로 증가함에 따라, 생체액의 호흡, 심박수, 피부온도, 신체 움직임, 체액내의 바이오 마커 등 생리정보를 지속적으로 모니터링하고, 개인의 건강상태를 실시간으로 진단할 수 있는 웨어러블 POCT 시스템의 개발이 절실히 요구되고 있습니다. 다양한 웨어러블 POCT 시스템 요소들 중, 웨어러블 바이오센서는 건강 상태와 아주 밀접한 관련이 있는 체액내의 바이오 마커를 지속적이고 직접적으로 감지할 수 있기 때문에 최근 엄청난 주목을 받고 있으나, 완벽한 실시간 연속 검출을 구현하기 위해서는 불충분한 신축성, 낮은 검출 정확도, 검출 환경에 대한 의존성 및 체액 혼합현상 같은 해결해야 할 몇 가지 문제가 여전히 남아있습니다.
웨어러블 바이오 센서의 신축성은 신체 움직임으로 인한 노이즈 신호발생을 방지할 뿐만 아니라 체액을 지속적으로 수집하기 위한 피부와의 등각 부착에도 매우 중요합니다. 따라서 비신축성 특성을 가진 소재에 신축성을 부여하기 위해, 바이오센서는 세방향으로 언덕과 골이 연속적으로 연결되어 있는 입체 마이크로 패턴을 가져, 물리적 변형에서 발생하는 응력을 효과적으로 흡수할 수 있는 모굴 기판에 제작되었습니다. 또한, 높은 표면적 대 부피비와 뛰어난 화학적 안정성을 갖는 나노 물질을 간섭 분자에 대한 검출 정확도와 검출 환경에 대한 검출 안정성을 향상시키기 위해 바이오 리셉터 대신 촉매로 사용하였습니다. 결과적으로, 모굴 패턴 기판 상에 제작된 나노촉매물질을 사용한 신축성 포도당 바이오센서들은 포도당에 대한 높은 감도, 간섭 분자에 대한 높은 선택성, 뛰어난 다방향 신축성 및 pH나 온도와 같은 검출 환경에 대한 낮은 의존성을 보여주었습니다.
다음으로, 연속적인 추출로 인한 체액 혼합을 방지하기 위해, 저렴하고 내구성과 생체 적합성이 뛰어나며 다양한 신축조건에서도 안정적으로 유체를 흡수하는 능력을 가진 신축성 면 소재 기반의 미세유체소자들이 개발하였습니다. 제작된 면 소재를 기반 미세유체소자들은 다양한 물리적변형에도 일정하고 안정적인 효율의 유체 처리 특성을 보여주었습니다. 마지막으로, 완전히 신축성이 있는 미세유체소자 통합 바이오센서 패치는 신축성 바이오센서를 신축성 미세유체소자와 집적하여 제작되었으며, 땀을 정밀하게 수집 및 처리하여 체액의 혼합 효과를 효과적으로 방지를 통해 높은 검출 정확도 및 신뢰도를 이뤄냈습니다.
결론적으로, 본 연구의 결과들은 현재 존재하는 실시간 연속 신체감지의 한계점들을 해결함으로써 개인화 된 예방 의학을 위한 웨어러블 바이오 센서플랫폼의 새로운 지평을 열어줄 것입니다.

목차 (Table of Contents)

• Chapter 1. Introduction 1
• 1.1. Wearable point-of care-testing (POCT) system 1
• 1.2. Wearable biosensor 4
• 1.3. Biofluids 6
• 1.4. Diabetes 9
• 1.5. Key challenges 13
• 1.6. Research design 15
• 1.6.1. Bio-receptor free detection using nanomaterials 15
• 1.6.2. Geometric engineered stretchable substrate 16
• 1.6.3. Capillary materials based microfluidic device 19
• 1.6.4. Overview of thesis 20
• Chapter 2. Nanoporous gold (NPG) synthesis for non-enzymatic detection 22
• 2.1. Introduction 22
• 2.2. Results and discussion 23
• 2.2.1. Structural and compositional analysis 23
• 2.2.2. Electrochemical characterization 25
• 2.3. Experimental section 28
• 2.3.1. Synthesis of nanoporous gold 28
• 2.3.2. Electrochemical measurements 29
• 2.4. Conclusion 30
• Chapter 3. Fully stretchable microfluidic-integrated non-enzymatic biosensor patch for wearable continuous glucose monitoring 31
• 3.1. Introduction 31
• 3.2. Results and discussion 34
• 3.2.1. Development of stretchable non-enzymatic glucose sensor 34
• 3.2.1.1. Sensitivity evaluation 38
• 3.2.1.2. Selectivity evaluation 41
• 3.2.1.3. Stretchability evaluation 43
• 3.2.1.4. pH/Temperature dependence 46
• 3.2.2. Development of stretchable cotton fabric-based microfluidic device 50
• 3.2.2.1. Polyurethane nanofibers reinforced PDMS cover characterization 50
• 3.2.2.2. Cotton fabric characterization 51
• 3.2.2.3. Fluid handling characteristics evaluation 55
• 3.2.3. Development of stretchable microfluidic-integrated biosensor patch 56
• 3.2.3.1. Wettability evaluation 57
• 3.2.3.2. Fluid replacement characteristics evaluation 58
• 3.2.3.3. Real-time on-body detection performance 63
• 3.2.3.4. Daily sweat glucose monitoring performance 65
• 3.3. Experimental section 68
• 3.3.1. Fabrication of stretchable non-enzymatic glucose sensor 68
• 3.3.2. Fabrication of stretchable microfluidic-integrated biosensor patch 70
• 3.3.3. In vitro electrochemical measurements 72
• 3.3.4. In situ electrochemical measurements 74
• 3.4. Conclusion 75
• Chapter 4. Platinum nanoparticles attached NPG (PtNPs@NPG) synthesis for selfpowered detection 76
• 4.1. Introduction 76
• 4.2. Results and discussion 77
• 4.2.1. Structural and compositional analysis 77
• 4.2.2. Electrochemical characterization 81
• 4.3. Experimental section 83
• 4.3.1. Synthesis of platinum nanoparticles on NPG 83
• 4.3.2. Electrochemical measurements 83
• 4.4. Conclusion 84
• Chapter 5. Stretchable fuel cell-based glucose sensor integrated with cotton threadembedded microfluidic for self-powered wearable glucose detection 85
• 5.1. Introduction 85
• 5.2. Results and discussion 88
• 5.2.1. Development of stretchable fuel cell-based glucose sensor 88
• 5.2.1.1. Fuel cell characteristics evaluation 90
• 5.2.1.2. Self-powered characteristics evaluation 93
• 5.2.2. Development of stretchable cotton thread-embedded microfluidic device 97
• 5.2.2.1. Evaluation of the absorptivity determinants 97
• 5.2.2.2. Cotton thread characterization 100
• 5.2.2.3. Design of elastomeric microfluidic layer 102
• 5.2.2.4. Fluid handling characteristics evaluation 105
• 5.2.3. Development of stretchable self-powered glucose sensor patch 107
• 5.2.3.1. Fluid replacement characteristics evaluation 108
• 5.2.3.2. Real-time on-body detection performance 111
• 5.3. Experimental section 113
• 5.3.1. Fabrication of stretchable fuel cell-based glucose sensor 113
• 5.3.2. Fabrication of stretchable self-powered glucose sensor patch 115
• 5.3.3. In vitro electrochemical measurements 117
• 5.3.4. In situ electrochemical measurements 118
• 5.4. Conclusion 119
• Chapter 6. Conclusion 120
• Reference 123