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

Abstract

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