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Design, fabrication and characterization of magnetically actuated microrobots for targeted cell transportation

Design, fabrication and characterization of magnetically actuated microrobots for targeted cell transportation
Translated Title
표적지향형 세포전달을 위한 자기장 구동의 마이크로로봇의 설계, 제작 및 특성평가
Kim, Sang Won
DGIST Authors
Kim, Sang Won; Choi, Hong Soo; Nelson, Bradley
Choi, Hong Soo
Nelson, Bradley
Issue Date
Available Date
Degree Date
2017. 2
MicrorobotsScaffoldsTargeted therapyMagnetic manipulationMicro-fabrication technologiesMEMS technologiesBio-inspired technologiesCiliary microrobots3D cell cultureStem cellStem cell differentiationStem cell therapy마이크로로봇지지체표적치료자기장 조작미세공정기술MEMS 기술생체모방 기술섬모 마이크로로봇3 차원 세포배양줄기세포줄기세포 분화줄기세포 치료
Magnetically actuated microrobots were developed as a platform for the cell study and targeted transportation. Fundamental microrobotics for biomedical applications including the targeted therapy, efficient propulsion methods in the micro-scale environment, fundamental principal of magnetic manipulation and electromagnetic coils systems were briefly explained in the beginning of thesis. Proposed microrobots were fabricated with microfabrication technologies including the three dimensional (3D) laser lithography to form the basic structures, and metal sputtering system for deposition of magnetic material and biocompatible material, and are precisely controlled with magnetic fields to swim in the fluid environments. Scaffold shapes of microrobots were fabricated to carry the cells into the specific target area with 3D cell cultured microrobots; bundle of cells are entangled on the porous microrobots. Structures of scaffold type microrobots were designed to apply the various propulsion mechanisms such as pulling, rolling, and Corkscrew motions with cylindrical, hexahedral, spherical, and helical shapes, etc. First, the cylindrical and hexahedral shapes of microrobots were designed and fabricated, which microrobots were manipulated by external magnetic field gradient to pull and push those bulky structures. The maximum averaged translational velocities were evaluated as 50 μm/sec for cylindrical microrobots and 35 μm/sec for hexahedral microrobots under the 800 mT/m of external magnetic field gradient in the de-ionized (DI) water, respectively. The velocities and those pulling translation mechanism would be not suitable for micro-scale swimming environment, because of the low Reynolds number fluid (high viscos force with low inertia force). To enhance the propulsion efficiency in this micro-scale swimming environment, the Corkscrew motion and rolling motion were suggested, and designed the helical and spherical shapes of microrobots, respectively with preserving the previous scaffold shapes. The maximum translational velocities were evaluated as 550 μm/sec for the helical microrobots and 1400 μm/sec for the spherical microrobots under 15 mT of magnetic field intensity and their step-out frequencies in the de-ionized (DI) water, which velocities were dramatically increased than previous cylindrical and hexahedral shapes of microrobots. The power efficiencies of developed four kinds of scaffold type microrobots were also compared among various microrobots developed, which defined as translational velocities per normalized current on the electromagnetic coils system. The power efficiencies for helical and spherical scaffold type microrobots were much higher than those of cylindrical and hexahedral shapes of scaffold type microrobots. Also ciliary microrobots were developed which also use one of the efficient propulsion mechanism in the low Reynolds number fluid inspired by microorganisms such as Paramecium which shows the non-reciprocal stroke motion to translate the body. The fabricated cilia, attached on the ellipsoidal body were manipulated by an electromagnetic coils system which generates stepping magnetic field to actuate the cilia with non-reciprocal motion. The cilia beating motion produces a net propulsive force to translate the microrobots. The magnetic forces on cilium were calculated with various input parameters including magnetic field, cilium length, applied field angle, actual cilium angle, etc., and the translational velocity was measured by experiments. Also the complex trajectory driving and the particle transport experiment were conducted to show the feasibility of the targeted cell or drug delivery. Developed scaffold type microrobots were also manipulated in the microfluidic channels, to show the possibility for microrobots to perform in the blood vessels, or confined environment. The human embryonic kidney (HEK) cell culture, and hippocampal neuronal stem cells (NSCs) culture and differentiation were completed for scaffold type microrobots to show the feasibility for targeted cell transportation. 3D cell cultured microrobots of NSCs were proliferated and the NSCs were differentiated into target cells composing brain tissues such as astrocytes, oligodendrocytes, and neurons. In summary, magnetically actuated microrobots were developed with various shapes with designated driving mechanisms such as four different shapes of scaffold types and ciliary type. Microfabrication technologies were used to form the basic 3D structures of microrobots, and nickel and titanium were deposited to manipulate by magnetic fields and for the biocompatibility. The position and orientation of developed microrobots were precisely controlled and the driving performances were evaluated and compared among the microrobots. The human embryonic kidney (HEK) cells were cultured on scaffold type microrobots. The hippocampal neuronal stem cells (NSCs) were cultured on scaffold type microrobots and differentiated into specific neuronal cells to show the possibility of NSCs therapy using microrobots. ⓒ 2017 DGIST
Table Of Contents
1. INTRODUCTION 11-- 1.1 Background 11-- 1.1.1 Medical microrobots 11-- 1.1.2 Microrobots for regenerative medicine 15-- 1.2 Research trend or related research works 18-- 1.2.1 Magnetic microrobots 18-- 1.2.2 Various driving mechanisms 20-- 1.2.3 Bio-scaffolds 23-- 1.3 Magnetic manipulation 25-- 1.3.1 Magnetic manipulation 25-- 1.3.2 Magnetic materials 27-- 1.4 Objective of research 31-- 2. DESIGN AND FABRICATION OF MICROROBOTS 32-- 2.1 Design and fabrication of scaffold type microrobots 32-- 2.1.1 3D laser lithography system for microrobots fabrication 33-- 2.1.2 Detailed fabrication process for scaffold type microrobots 37-- 2.2 Design and fabrication of scaffold type microrobots with higher propusion efficiencies 39-- 2.3 Design and fabrication of ciliary microrobots with higher propusion efficiency 45-- 2.4 Design and fabrication of microfluidic channels as in-vitro test platforms 48-- 3. MAGNETIC MANIPULATION OF MICROROBOTS 51-- 3.1 Magnetic manipulation of magnetic materials 51-- 3.2 Pulling motion with scaffold type microrobots 53-- 3.3 Rolling and Corkscrew motion with scaffold type microrobots 58-- 3.4 Stroke motion with ciliary microrobots 63-- 3.5 Manipulation of microrobots in the microfluidic channels 73-- 3.5.1 Manipulation in the static fluidic channel 73-- 3.5.2 Manipulation in the pressure driven channel 74-- 4. CELL CULTURE AND DIFFERENTIATION EXPERIMENTS 78-- 4.1 Human embryonic kidney 293 cells culture on microrobots 78-- 4.1.1 Cell culture and SEM inspection 79-- 4.1.2 Immunocytochemistry assay 80-- 4.2 Hippocampal neural stem cells culture on microrobots 81-- 4.2.1 Detailed protpcols for Hippocampal NSC culture and differentiation 84-- 4.2.2 Analysis and cell counting 84-- 5. CONCLUSIONS 87
Robotics Engineering
Robotics EngineeringThesesPh.D.

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