Wearable systems that monitor bio signal, store data and deliver feedback therapy are the next frontier in personalized medicine and healthcare. This emerging class of electronics includes sensors, light-emitting diodes and associated circuit components that interface with in-ternal organs (such as the heart and brain) and skin (or artificial skin scaffolds). However, a key constraint of these flexible and stretchable electronics for wearable biomedical devices lies in their inability to store recorded data in memory modules during continuous, long-term monitor-ing. Another desirable feature missing in emerging wearable devices is the ability to deliver ad-vanced therapy in response to diagnostic patterns present in the collected data. In this thesis, to realize the wearable systems for theragnosis, flexible phase change memory, drug delivery sys-tems and integrated smart contact lens were demonstrated using several fabrication processes for inorganic based flexible devices.
In chapter 2, flexible memory is the fundamental component for data processing, storage, and radio frequency communication in flexible electronic systems. Among several emerging memory technologies, PRAM is one of the strongest candidate for next-generation nonvolatile memories (NVMs) due to its remarkable merits of large cycling endurance, high speed, and excellent scalability. Although there are a few approaches for flexible PCM, high reset current is the biggest obstacle for the practical operation of flexible PCM devices. In order to achieve the low switching current, the contact area between a phase-change material and a heater should be shrunk through the further scaling-down. However, the conventional optical lithography has been restricted because of the limit of optical resolution on flexible substrates. In this paper, we report a flexible PCM realized by incorporating nano-insulators derived from a Si-containing block copolymer (BCP) to significantly lower the operating current of the flexible memory formed on plastic substrate. The reduction of thermal stress by BCP nanostructures enables the reliable operation of flexible PCM devices integrated with ultrathin flexible diodes during more than 100 switching cycles and 1,000 bending cycles. By integrating high-performance single crystal silicon diodes with PCM, cell-to-cell interference between adjacent memory cells is ef-fectively prevented on a plastic substrate.
In chapter 3, there is no doubt that controlled and pulsatile drug delivery system (DDS) is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. Because they deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and in-creased patient compliance. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for controllable and pulsatile drug delivery sys-tems. However, MEMS based DDS using the rigid and bulky semiconductor chips have limited its uses as in vivo devices due to incongruent contact with the corrugated and curved surfaces of organs such as the brain, eye, and heart. Here, we introduce a conceptual strategy for the fabrication of flexible DDS with SU-8 reservoirs on a plastic substrate via a laser lift-off (LLO) process. The developed flexible device demonstrated reliable operation with excellent mechan-ical stability on a plastic substrate. Flexible drug delivery array system (f-DDS) which can be inserted through a small cranial slit and stably wrap onto the curved cortical surface. Fluores-cence experiment demonstrates that Au thin membrane which sealing the drug reliably dis-solved on the brain surface when electrical power was applied with the current of few $\mu A$ within tens of second.
In chapter 4, over the last few years, wearable devices that monitor physiological activi-ties for diagnosis and therapy are considered to be a promising candidate in the field of person-alized healthcare. In particular, smart contact lens as a minimally invasive platform for diagnos-tics and drug delivery has recently emerged. However, a key issue of the contact lens as a wearable biomedical device is its inability to deliver advanced therapy to patients, in response to the embedded sensor output. Continuous monitoring and corresponding treatments are crucial for the patients who need daily care, especially with diabetes and degenerative diseases such as cornea neovascularization. In this work, we demonstrate a genuine integrated bio-compatible smart contact lens, which is potentially a novel solution for theragnosis of such dis-eases. The developed contact lens system consists of four miniaturized components - wireless power transfer system by resonant inductive coupling, CMOS IC-based microcontroller chip, real-time electrochemical biosensor, and self-regulated pulsatile drug delivery system. Recorded by commercially available wireless communication electronics, simultaneous monitoring and treatments by the contact lens system for cornea neovascularization using in vivo rabbit models are presented.
본 학위논문은 웨어러블 헬스케어 시스템에 적용 가능한 유연한 상변화 메모리와 약물전달 소자에 관한 내용으로 작성되었다. 특히 소프트 리쏘그래피와 레이저 리프트 오프 방식의 다양한 전사 기술을 이용한 유연 메모리와 약물전달 소자 구현 및 특성평가, 응용에 관한 연구를 중점적으로 진행하였다.
챕터 2에서는 상향식 방법인 자기 조립 기술로 우수한 성능의 유연 상변화 메모리를 구현하였다. 블록공중합체 자기조립이 유연 상변화 메모리에 성공적으로 적용하여 작동 전류를 4배 감소시켰다. 시뮬레이션 결과를 통해 자기조립된 실리카 나노구조가 유연 상변화 메모리의 열구배를 효과적으로 조절함을 확인하였다. 게다가, 우수한 성능의 단결정 다이오드를 스위칭 소자로 유연 상변화 메모리에 연결하여 셀간 전기적 간섭문제를 해결하였다. 내구성, 장기 기억 실험, 통계분석을 통해서 안정적으로 소자가 작동함을 확인하였다. 굽힘 피로 실험과 이론적 계산을 통해서 우수한 기계적 안정적을 확인하였다. 이 기술은 롤투롤 시스템을 기반으로한 블록공중합체 자기조립 기술을 통해 저렴하게 대량생산 라인에 적용할 수 있을 것으로 생각된다.
챕터 3 에서는 레이저 리프트 오프 공정을 이용한 유연 약물전달 소자를 움직이는 쥐에 국부적으로만 약물을 전달가능한 형태로 성공적으로 개발하였다. 레이저 리프트 오프 공정을 이용하여 유연 약물전달 소자는 단단한 기판에서 상용화된 마이크로 제조기술로 제조한 후 유연한 기판 위에 기계적 결함없이 전사하였다. 금막으로 덮혀있는 얇고 유연한 SU-8 약물 저장소는 두개골의 작은 틈을 통해 매끄럽게 삽입될 수 있게 만들어졌고, 이 소자를 이용하여 두개골 밑의 울퉁불퉁한 대뇌 피질층에 성공적으로 약물을 전달하였다. 이 기술은 마이크로 벨브, 센서, 반도체 제어칩과 연결가능하여 피드백을 통한 특정 위치, 시간, 양이 조절된 약물 전달 또한 가능할 것이다.
챕터 4에서는 챕터 3에서 개발한 약물전달 소자를 이용하여 진단 및 치료가 가능한 스마트 컨텍트 렌즈를 구현하였다. 컨텍트 렌즈를 구성하는 바이오 센서, 약물전달 소자, 무선 제어 칩은 각각 안정적인 작동을 함을 전기적 실험으로 확인하였다. 이 컨텍트 렌즈는 일일 건강 진단을 위해 실시간 질병 진단용 바이오 센서, 조절 가능한 맥박 형태의 약물전달 소자, 무선 제어 칩을 하나의 기판에 집적하여 제작하였다. 진단 및 치료가 가능한 스마트 컨텍트 렌즈는 다양한 질병의 유비쿼터스 건강 관리를 위한 차세대 나노 치료 시스템으로 연구되어질 것이다.
