Fabrication and characterization of flexible memory and drug delivery device for wearable healthcare system

Abstract

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.