Optical properties of GaP photonic crystal nanobeam cavity with WSe2 active monolayer

이호성 KU-KIST Graduate School of Converging Science and 2020 국내석사

인화 갈륨 나노빔 공진기와 이차원 반도체의 광특성 이 호성 고려대학교 KU-KIST 융합대학원 지도교수: 박 홍규 국문 초록 이차원 반도체의 새로운 물리적 특성은 저차원 물리 및 장치 응용분야의 새로운 장을 열었습니다. 이 물질들이 하나의 전이금속 원자가 양쪽에 할로겐 원자에 갇혀있는 X-M-X 구조를 가집니다. 이 물질들은 같은 평면방향으로 강한 결합을 하고 있으며, 매우 얇고, 유연합니다. 그리고 가장 큰 특징은 원자 두께 정도지만, 반도체의 특성인 직접적인 밴드갭을 갖고 있습니다 [38,39]. 또한, 이차원 물질은 강한 여기방출을 하는 것으로 알려져 있습니다. 따라서, 이차원 물질은 광결정 공진기에서 이득 매질로 사용될 수 있습니다 [36,37]. 나노 크기의 높은 품위값을 갖는 나노빔과 텅스텐 디셀레나이드(WSe2) 단층과의 통합은 광 집적 회로에 기여할 수 있습니다. 인화 갈륨은 가시광선 영역에서 가장 높은 굴절률( 555 nm 에서 3.44)을 가지는 물질입니다. 인화 갈륨으로 나노빔 공진기를 만들어 텅스텐 디셀레나이드와 결합시키려고 합니다. 하지만, 인화 갈륨은 박막 형태로 기르기 힘들기 때문에, 베어 웨이퍼에 집속 이온빔 (FIB) 장비를 이용해서 삼각형 형태의 나노빔 공진기를 만들 것입니다. 그리고, 유한 차분 시간 시뮬레이션(FDTD)을 통해 삼각형 나노빔 공진기를 설계하였습니다. 삼각형 형태지만, 인화갈륨의 굴절률이 높기 때문에 〖10〗^6 의 높은 품위값을 가집니다. 희생층이 없기 때문에 두 번의 건조 식각 공정을 거칩니다. 나노빔 공진기의 위, 아래 부분과 구멍들을 일차적으로 식각합니다. 그 다음, 집속 이온 빔으로 기울여서 밀링 공정을 통해 제조될 것입니다. 제작된 나노빔 공진기 위에 텅스텐 디셀레나이드 단층을 옮긴 뒤, 측정을 진행할 것입니다. 이차원 반도체 물질의 광발광의 두께가 얇아지거나, 공동과 결합될 것으로 예상됩니다

Micromagnetic study of chiral magnetic systems

이승재 KU-KIST Graduate School of Converging Science and 2020 국내박사

Magnetic systems in the presence of Dzyaloshinskii-Moriya interaction (DMI) is named as chiral magnetic systems as DMI in magnetic systems contributes to the stabilization of chiral magnetic textures (i.e. chiral domain wall and skyrmion). DMI stabilizes chiral magnetic states as DMI energy prefers spatially tilted magnetization by competing with other magnetic energies (mainly exchange energy and anisotropy energy). The DMI is an antisymmetric part of exchange interaction and arises when the magnetic system has exchange interaction, spin-orbit coupling and inversion symmetry breaking. Especially, bilayer composed of a heavy metal layer and a magnetic layer satisfies those prerequisites at the interface. This is because, basically, the bilayer system has inversion symmetry breaking at the interface, the exchange interaction is given from magnetic layer, and a large spin-orbit coupling is given from heavy metal layer. For these reasons, magnetic bilayer structures with DMI have been intensively investigated because chiral domain walls and skyrmions are considered as one of the candidates for making use of the racetrack memory. As mentioned, the DMI in bilayer highly depends on the interface therefore it is opening large potential in material design. Furthermore, the chirality of magnetic systems also affects the spin-wave propagation according to wave vector of spin wave and makes nonreciprocal propagation of spin waves in a nanowire. This nonreciprocity opens other approaches in various functional devices with spin wave and offers rich spin-wave physics. In this thesis, we introduce analytical and numerical results for current induced skyrmion motions and spin-wave propagations in chiral magnetic systems.

Multichannel nerve guidance conduit with stem cell recruitment ability for enhanced nerve regeneration

박도연 KU-KIST Graduate School of Converging Science and 2020 국내박사

수천 개의 신경섬유의 재생 방향을 조절하고 재생 환경을 조성하는 것은 말초신경손상과 척수신경손상에서의 재생능을 향상시키는 데에 있어 매우 중요하다. 현재까지 존재하고 있는 많은 치료법과 연구들은 아직 위와 같은 조건들 없이, 많은 문제점들을 가지고 있다. 현재까지 최우선 치료법으로 여겨지고 있는 자가/동종신경이식의 경우, 수급 부족의 문제뿐 아니라 수여자 조직과 공여자 조직 간의 크기 차이의 문제가 큰데, 후자의 경우 신경종이 생길 수 있다. 단일채널 신경도관의 경우는 물리적인 조절/유도 장치가 없어 잘못된 연결을 일으킬 수 있다. 또한, 단일채널 신경도관에 줄기세포 등의 세포를 배양하여 이식하는 경우 안전의 문제를 간과할 수 없다. 따라서, 이러한 모든 문제들을 모두 해결하는 새로운 도관의 개발을 위해 많은 연구가 진행되고 있다. 이를 위한 대표적인 제작방법은 thermal drawn 방법과 3D 프린팅 방법이 있다. Thermal drawn 방법은 가열된 상태에서 고분자를 압출시키는 방법이며, 3D 프린팅은 고분자를 원하는 위치에 쌓아올리는 방법이다. 하지만, 이러한 방법으로 제작된 신경도관도 여러 한계를 갖고 있고, 실제 자가/동종신경이식만큼의 재생효율을 보여주지 못하고 있다. 또한, 여러 생체적합한 물질들을 이용하여 신경재생의 효율을 증가시키려는 노력 또한 진행되고 있다. 하지만, 재료만 가지고 신경을 재생시키는 방법은 신경섬유의 재생방향을 조절하지 못한다는 명확한 한계를 가지고 있다. 이에 따라, 많은 연구자들은 더 나은 신경재생을 위해서는 제작방법의 진보와 재료연구의 복합적인 융합연구가 필요하다고 지적한다. 본 박사학위 논문에서는 마이크로칩 기술과 고분자 공학의 융합으로 발전된 신경재생능을 일으킬 수 있는 신경도관을 제작하였다. 마이크로칩 기술은 미세구조의 크기 및 수치까지 조절가능하며, 고분자공학은 기존 고분자의 성질을 변화시킬 수 있기에 이 논문에서는 이러한 장점들을 융합함으로써, 수치 조절이 가능한 미세채널을 수 백개 가지고 있으며 능동적으로 내부환경을 재생에 적합하게 바꿔주는 신경도관을 제작하였다. 그 개념을 간단히 아래와 같다. Poly(L-lactide-co-ε-caprolactone) (PLCL) 고분자를 클로로포름 용액에 녹인 고분자 용액을 요철의 반복되는 미세패턴을 가지고 있는 PDMS mold에 넓게 도포한 후, 그 채로 메탄올 배지에 넣어 PLCL이 패턴을 가진 채 석출되도록 하였다. 그런 후, 패턴을 가진 PLCL sheet를 미세패턴에 수직인 방향으로 굴려주면 PLCL sheet의 패턴이 새겨진 부분과 패턴이 새겨지지 않은 부분이 만나면서 패턴의 들어간 부분 개수만큼의 미세채널이 형성된다. 여기서, PLCL-SP (substance P(SP)가 공유결합된 PLCL)을 일정비율로 섞어서 사용한다면, 줄기세포 유도능이 있는 SP로 인해 수백 개의 미세 채널로 수여자의 줄기세포가 모여들어 재생을 도울 수 있을 것이다. 완전한 형태의 미세채널을 갖는 신경도관의 제작을 위해서 미세패턴의 디자인이나 PLCL 고분자 용액의 농도 등의 요소들이 최적화되었다. 말초신경손상 모델에 본 신경도관이 이식되어 미세채널에 의해 신경재생의 방향을 조절하는 것과 SP에 의해 줄기세포 유도능을 갖는 것이 확인되었으며, 이러한 특징들이 신경재생에 어떤 영향을 끼치는지에 대한 정량적인 분석이 진행되었다. 또한, 척수신경손상 모델에 대해서도 같은 측정이 진행되어 본 신경도관이 척수신경손상 모델에 사용될 수 있는 가능성을 제시했다. 마지막으로, 위의 신경도관 모델이 재생을 위한 다른 많은 방향에서도 사용될 수 있음을 보이기 위해 전반적인 모양을 변형시켜 분지된 형태의 신경도관을 만들거나 수백 개의 미세채널 내에 지형적 신호 (topographic cue)를 새겨넣는 것을 보였다. 즉, 이 논문에서 제시한 신경도관 제작방법, 즉 마이크로칩 기술과 고분자 공학의 융합을 기반으로 한 제작방법은 앞으로 추가적인 발전가능성이 있어, 추후 말초신경 및 중추신경 손상에 대한 새로운 치료법으로 발전할 수 있다고 할 수 있다. Guiding the regrowth of thousands of nerve fiber within a regeneration-friendly environment enhances the regeneration capacity in peripheral nerve injury (PNI) and spinal cord injury (SCI). Although there exist current clinical treatments and various researches, all have their critical limitations that no seamless results have been found. Autograft/allograft, regarded as gold standard so far, has not only a scarcity problem but also the size difference problem, which could induce neuroma formation. Single-channel nerve guidance conduit (NGC) increases the induction of erroneous re-innervation due to the absence of the alignment cue in it. Also, single-channel NGC seeded with cells, especially stem cells, has a safety issue. Accordingly, various trials to develop NGC desirable for nerve regeneration have preceded. Representative fabrication approaches for NGC include a thermal drawn method and 3D printing. Thermal drawn method employs the heated extrusion for the production of polymer-based NGC, and 3D printing is stacking the polymer at the desirable site to build NGC with pre-defined design. However, NGCs fabricated by each method differ from the native nerve tissue very much and often followed poorer results than the autograft/allograft did when implanted. Also, various biocompatible materials have been developed to enhance nerve regeneration. However, the material-only approach has a definite limitation that the direction of nerve regrowth is hardly controlled. Therefore, combinatorial approaches are needed to fabricate desirable and nerve-tissue like NGC. In this paper, NGC with improved capability for nerve regeneration was produced by the convergence of microchip technique and polymer engineering. Since microchip technique has the advantage of controlling each dimension of the microstructure, and polymer engineering has the advantage of modifying the characterization of the polymer, NGCs produced in this work have a controllable size of length, diameter, and the microchannels, and can actively form the regeneration-friendly environment within the microchannels. Poly(L-lactide-co-ε-caprolactone) (PLCL) dissolved in chloroform was bathed in a methanol solution to result in precipitation of PLCL onto a polydimethylsiloxane (PDMS) mold (width*length = 12 mm * 40 mm) engraved with repeated ridges and grooves. Rolling the precipitated PLCL substrate, on which micropatterns of ridges and grooves were engraved, makes the patterned part of the substrate meet the planar part of the substrate, forming multiple microchannels. Here, PLCL-SP, PLCL immobilized with substance P (SP) that is a well-known stem cell recruitment factor, was employed to achieve a NGC with hundreds of microchannels having stem cell recruitment ability. Various factors including micropattern design and PLCL concentrations were explored for the optimized form of multichannel NGC. Neuronal alignment and regeneration along these microchannels and the action of SP for enhanced regeneration after PNI were verified, followed by measuring quantitative parameter for directing the enhanced nerve regeneration capacity of NGC fabricated in this study. Next, the same measurement was conducted for the implantation to the SCI model. This suggested the possibility of this NGC be used as SCI treatment. Finally, to assess the ability to use the proposed NGCs in diverse applications, we suggested a modified and augmented form of NGC by showing bifurcated morphology of mNGC or adding directional topographies on the microchannels. Additional improvements in the fabrication process will advance the development of regeneration research and treatment for peripheral/central nerve injury.

Role of orbital hybridization in anisotropic magnetoresistance

고혜원 KU-KIST Graduate School of Converging Science and 2020 국내석사

In this thesis, we theoretically and numerically show that longitudinal orbital currents in ferromagnets depend on the magnetization direction, which contribute to the anisotropic magnetoresistance (AMR). This orbital contribution to AMR arises from the momentum-dependent orbital splitting, which is generally present in multiorbital systems through the orbital anisotropy and the orbital hybridization. We highlight the latter orbital hybridization as an unrecognized origin of AMR and also as a common origin of AMR and orbital Hall effect. In Chapter 1, we present theoretical context of our work. Then, in Chapter 2, we theoretically analyze the AMR in terms of orbital degrees of freedom. The simple model demonstrates how the orbital hybridization alone induces the orbital splitting and causes the anisotropic conduction. An analytical derivation of magnetization-dependent conductivity is also shown by perturbation theory. Numerical results, in which two orbital factors are treated independently, manifest that the orbital physics act as underlying mechanism of AMR. The results given in this thesis provide deeper understanding on AMR and call for systematic investigation on AMR with consideration of orbital hybridization. 본 논문은 강자성체에서 자화와 스핀-궤도 결합(spin-orbit coupling)에 의해 발생하는 이방 자기저항(anisotropic magnetoresistance)을 오비탈 자유도의 관점에서 분석하고자 한다. 이론과 수치 모사를 통해 강자성체에 전기장을 인가한 방향으로 흐르는 오비탈 전류 전도도가 자화 방향에 의존하며 이방 자기저항에 기여하는 것을 확인하였는데, 이 자화 의존성은 운동량에 따른 오비탈 에너지의 분할이 존재하기 때문으로 밝혀졌다. 이러한 오비탈 에너지의 양상은 다중 오비탈 계에 일반적으로 내재되어 있는 오비탈 이방성(orbital anisotropy)과 오비탈 혼성화(orbital hybridization)에서 기인한다. 이 중 오비탈 혼성화는 본 연구를 통해 새롭게 밝혀진 이방 자기저항의 원인으로 오비탈 홀 효과(orbital Hall effect)와 같은 스핀트로닉스의 주요한 현상들을 야기하는 요인임을 보이고자 한다.

(A) study on activatable strategies for targeting signals in the innate immune system

고영지 KU-KIST Graduate School of Converging Science and 2020 국내박사

The activatable strategies have been emerged as advanced tools for imaging and treatment of various diseases by allowing it to increase their effectiveness under certain conditions. First, activatable imaging probes have been developed to decrease the background noise and boost their signal under the certain circumstance. They are designed to respond to specific targets, allowing real-time observation of biological processes associated with targeting signal occurring at the cellular level. Therefore, they can be applied to monitor biochemical changes in various diseases, thereby helping us to diagnose and treat various diseases. Second, activatable strategies can be used as new treatments to reduce the side effects of drugs by designing them to show pharmacological effect only in certain situations. Among the causes of various diseases, homeostatic destruction of the innate immune system causes various serious inflammatory diseases such as Alzheimer's disease, cancer, and sepsis etc. Although the failure of innate immune homeostasis causes a variety of diseases associated with inflammatory diseases, the system has not been fully understood, and more research has been needed on targets that cause the disorder. Therefore, applying activatable strategies to specific targets involved in the innate immune system can provide valuable information for understanding and treating a variety of inflammatory diseases. This study focuses on the application of activatable strategies that can respond to specific enzymes or receptors associated with the innate immune system. Specifically, the study showed that the activatable strategy can be successfully applied to the study of the innate immune system by targeting the caspase-1 enzyme associated with activation of the innate immune system and the CD47 receptor involved in the inhibition of the innate immune system. First, caspase-1 activatable probe was developed to monitor the caspase-1 activation in various inflammatory disease mouse models such as inflammatory bowel disease, cancer, and Alzheimer's disease. The results demonstrated that Caspase-1 activatable probe could apply to monitor the active caspase-1 in the inflammatory disease models at an early stage of the diseases. Furthermore, interestingly, cancer uses an immune evasion mechanism, one of which is to induce "Don't Eat Me" by overexpressing CD47 on the surface. CD47-mediated activatable theragnostics, which can target the negative innate immune checkpoint; CD47, were applied to imaging and treatment in cancer models. The results showed that this strategy can efficiently target the cancer overexpressed by CD47 and enhance the anti-cancer effect by stimulating macrophage phagocytosis to cancer cells. In conclusion, activatable strategies targeting specific enzymes and proteins in the innate immune system can be applied to a variety of inflammatory diseases and can help in the early monitoring and treatment of these diseases.

Two-photon probes for HER-2 receptor, golgi apparatus, endoplasmic reticulum, and amyloid-β.

최지우 KU-KIST Graduate School of Converging Science and 2020 국내박사

Two-photon microscopy (TPM) employing two near-infrared (NIR) photons as the excitation source has emerged as a new and indispensable tool in biomedical research due to the advantages it offers. They include deeper penetration depth (more than 500 ㎛), intrinsically localized emission, lower photo-bleaching and photo-damage, and minimum background emission, as compared with one-photon microscopy. As such, TPM can monitor the biological activities deep inside a probe-labeled tissue for an extended period. However, the progress in this field is limited by the lack of useful TP probes for specific applications. This dissertation describes the design, synthesis, and biomedical application of new TP probes that can detect HER-2 receptor, Golgi apparatus, Endoplasmic reticulum, and Amyloid-β in live-cell and living tissues. Chapter 1 summarizes the fundamental principle of two-photon absorption (TPA) and the advantages of TPM over conventional fluorescence microscopy. Chapter 2 describes the synthesis of a two-photon tracer, Pyr-affibody, capable of detecting HER-2 receptors, and detecting the overexpressed HER-2 receptor in a live cell and breast cancer in the mouse model by TPM. Chapters 3 and 4 discuss the synthesis of two-photon tracers for the Golgi apparatus and Endoplasmic reticulum, respectively, and the detection of such organelles in live cells and tissues by dual-color TPM imaging. Chapter 5 describes the synthesis of two-photon tracer for Alzheimer’s disease, PyrPeg, and the detection of the neuritic plaques in in vitro, ex vivo, and in vivo models by TPM. The TP probes developed in this research are a promising tool for monitoring such targets in living systems. Therefore, the design strategy employed in this research can provide a useful guideline for the design of other TP probes for specific applications.

Control and analysis of electromagnetic wave transmission of multilayer thin film by transfer matrix method

권지성 KU-KIST Graduate School of Converging Science and 2021 국내석사

We propose and demonstrate that the Transfer matrix method can effectively analyze states of electromagnetic waves scattered from thin material. In this paper, we have studied the electromagnetic waves in metamaterials at a frequency range of X-band electromagnetic wave and infrared light. To analyze the scattered electromagnetic waves for the X-band range, the annealed Ti3CNTx film was modeled as a multilayer structure referring the experimentally measured electrical conductivity and the porous structure. The EMI SE increment of the annealed Ti3CNTx film was measured at a temperature as high as 350 ℃, at the same time, the material’s conductivity was around 1000 to 1800 S∙cm^(-1) and porosity rose from 0 to 16 %. The experimentally measured EMI SE increment of the annealed Ti3CNTx film can be explained theoretically by conductivity and porosity increment calculation of multilayer. For the infrared light range, a perfect anti-reflector was designed and manufactured. The UIM theory provides anisotropic parameter of a layer to eliminate reflection. The theoretical based UIM layer was designed as a sub-wavelength scale multilayer structure and calculated by the transfer matrix method. This UIM layer suppressed reflection under 1% from wavelength of 1.2 to 2.5 μm and incident angle from 0 to 50°. The fundamental UIM theory is applied to the manufacturing process of Si substrates. Furthermore, the reflectivity of the manufactured UIM layer was measured experimentally, and this reflectance was almost identical to that of stimulated. In this research, the transfer matrix method contributes in estimating the state of scattered electromagnetic waves in the thin multilayer structures.

Epidermal electronics system for physiological monitoring in patients with skin wound

최종찬 KU-KIST Graduate School of Converging Science and 2021 국내석사

While conventional wound assessments need to visit clinicians or help from nurse, there might be potential opportunities to develop an electronic system that can diagnose wound conditions by itself in a real time format, and can ultimately be managed unattended in medical systems. Here, we report a skin-interfaced wireless medical device that can diagnose wound status of patients in a real-time, personalized approach. This epidermal electronics system is systemically composed of two sub modules; a disposable sensor-integrated dressing (unit 1) and a reusable secondary wound enclosure incorporated with wireless communication electronics (unit 2). A mechanically soft, disposable unit 1 that consist of conventional medical dressings integrated with epidermal electronics sensor arrays (EESA) is capable of conformally attaching to the human skin and comprehensive, continuous monitoring of wound-status-related physiological parameters, including pH, temperature, and humidity. A reusable wireless modular unit 2 that utilizes electronic systems constructed on a flexible printed circuit board (FPCB) is contained within a soft, elastomeric housing and offers capabilities in analyzing bio-signals collected from EESA, diagnosing a patient’s status on healing phases, and transmitting data via wireless communications. This new platform illustrates their potential abilities for clinical uses through in vitro and in vivo investigations, and an example mobile application presents further applicability in a patient’s care.

Localized synergistic PLGA nanomedicines triggering effective anti-tumor immunity

최용환 KU-KIST Graduate School of Converging Science and 2021 국내박사

Over the past half century, cancer therapy has developed by presenting alternatives to the deficiencies of the previous generation. Actually, the paradigm of cancer treatment has changed until immunotherapy, the 3rd generation of cancer therapy, leading safe and powerful customized treatments. Ultimately, the core technology to treat cancer is using immune system of our body in a direct or indirect way. This approach provides us safety from the side effects, including unwanted toxicity, of the cancer treatment process. Unfortunately, there are still several obstacles originating from the tumor and its environment. Since the microenvironment of each tumor also has distinct characteristics from an immunological point of view, there is a clear limitation in that the responsiveness and efficacy of cancer immunotherapy can vary greatly from situation to situation. The point of this study is that application of nanomedicine-driven chemo-immunotherapy with a combination of several immunological drugs would overcome the problems of previous generation of cancer therapy, and they also expand the scope of application of cancer immunotherapy. In the point that nanomedicine technology is absolutely necessary to control the tumor environment advantageously for immunotherapy, DOX-loaded PLGA NPs, for controlled ICD, were prepared. Subsequently, several combinations of immunotherapy using anti-PD-L1 Ab and ROCK inhibitor were attempted with this base nanomedicine technology. DOX-PLGA nanomedicine is administrated by intratumoral injection, resulting in sustained release of DOX, leading to continuous ICD, sequentially. It came to appear as a result of induced anti-tumor immunity. Additionally, normalizing adaptive immunity by combination of DOX-PLGA nanomedicine and anti-PD-L1 Ab boosted T cell-mediated immunity. It successfully triggered systemic immune responses in tumor rechallenge model by inhibiting its growth. Similarly, enhancing innate immunity by combination of DOX-PLGA nanomedicine and Y27632, a type of ROCK inhibitor, also showed therapeutic efficacy in tumor growth and elicited anti-tumor immune responses. Unlike conventional mono-immunotherapy, modulating immune responses in tumor and its environment and inducing systemic anti-tumor immunity were made possible by DOX-PLGA nanomedicine-based cancer chemo-immunotherapy. And it is thought that this can enhance the accessibility of treatment as a platform technology for numerous other cancer immunotherapies.

Multi-functional cancer vaccine based on ROS-responsive photoswitching nanocomposites

조유리 KU-KIST Graduate School of Converging Science and 2021 국내석사

Cancer treatment techniques have significantly been advanced in recent decades, but they have a disadvantage of remarkably lowering the immune system in the body. To overcome this issue, immunotherapy is suggested to stimulate the immune system of humans to increase the effectiveness of cancer treatment. Strategies of cancer immunotherapy include immune checkpoint therapy, adoptive cell transfer, and cancer vaccine therapy. Recently, Uric acid (UA), the metabolic end-product of purine metabolism in humans, has been used as an adjuvant in immunotherapy. The crystalline Uric acid (MSU), the leading cause of gout, is known as damage-associated molecular patterns (DAMPs), which are the starting point for triggering the immune effector including dendritic cells and macrophages. In this paper, I devised a photo-switching Nanogel cancer vaccine based on the crystallization of UA, which can be triggered by photodynamic therapy (PDT) via an on-off system for enhancing immune responses. MSU produced after PDT was confirmed using TEM, suggesting that crystallization of UA can be controlled through an on-off system by PDT. The cell penetration efficiency, intracellular distribution, and photo-induced cytotoxicity of the Nanogel were evaluated by in vitro studies on a cancer cell line. Further, the immunogenic efficacy was evaluated by quantitative analysis of DAMPs expression on a cancer cell line.