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1. INTRODUCTION
In recent years, micro-devices intended to drive in the living body have been developed. These robotic agents, as capsule endoscopes, are expected to develop new medical treatments. However, these systems could function only to whole of an organ and a cell but not to the smaller one as a intracellular region because of its hugeness. On the other hand, in medical field, it has been revealed that organelles are in intracellular regions and which has important function related with the cell activity. Thus, many researches of organelle function controls have ever been reported, but most of these proposed methods were chemical and electrical stimuli of whole of a cell.
Then, we focused on the MEMS techniques. While a cell is tens of µm in size, most of organelles are few µm in size. So the intracellular agents are also required that the scale is smaller than a cell. In this paper, we report method of fabrication and driving of micro-nano device, and introducing into cell.
Concept image of the intracellular nano-robot
Micro-Electro-Mechanical Systems, or MEMS, is a technology that in its most general form can be defined as miniaturized mechanical and electro-mechanical elements that are made using the techniques of micro fabrication. The critical physical dimensions of Micro-Electro-Mechanical Systems devices can vary from well below one micron on the lower end of the dimensional spectrum, all the way to several millimeters. Likewise, the types of Micro-Electro-Mechanical Systems devices can vary from relatively simple structures having no moving elements, to extremely complex
electromechanical systems with multiple moving elements under the control of integrated microelectronics. The one main criterion of Micro-Electro-Mechanical Systems is that there are at least some elements having some sort of mechanical functionality whether or not these elements can move. The term used to define Micro-Electro-Mechanical Systems varies in different parts of the world. In the United States they are predominantly called Micro-Electro-Mechanical Systems while in some other parts of the world they are called “Microsystems Technology” or “micromachined devices”.
The initial development of the fabrication processes which enabled Micro-Electro-Mechanical Systems technology to be the current state-of-the-art in miniaturization, the entire community is still sitting on a silicon-based material palette. Although the number of new applications is growing at a tremendous rate, researchers and industry are facing a challenging problem of material selection because of the low availability of alternatives. In more recent years, new materials such as polymers, photo curable resists, metal alloys and others have appeared to be used in conjunction with integrated circuit (IC) technology. Nevertheless, some of the more envisioning and promising applications (such as biosensors for life science, micro/nano electrochemical and chemical sensing devices, etc.) have not yet found suitable materials for their optimal fabrication
In nature carbon is a very special element as the essential building block of most organic life. But also in human enterprise carbon in its various forms has acquired an enviable position. To just name a few: diamonds are made of carbon and also graphite, coke, and glassy carbon are all forms of carbon. So are the more recently discovered buckyballs, carbon fibers and carbon nanotubes .The utilization of carboneous materials has already begun in the above mentioned application fields as the widely different crystalline structures and morphologies of these materials enable different physical, chemical, mechanical, thermal and electrical uses , especially in life sciences applications because of its high biocompatibility.Recent developments in C-MEMS (Carbon-Microelectromechanical Systems), based on the pyrolysis of patterned photoresist at different temperatures and at different ambient atmospheres. Carbon Micro-Electro-Mechanical Systems describes a manufacturing technique in which carbon devices are made by treating a pre-patterned organic structure to high temperatures in an inert or reducing environment. It has been shown recently that 3D high-aspect-ratio carbon structures can be made from patterned thick SU-8 negative photoresist layers .SU-8 negative photoresist is a high transparency UV photoresist that enables creation of ” structures using traditional UV photolithography. .
2. MATERIALS AND METHODS
2.1 THE DESIGN OF THE INTRACELLULAR ROBOT
The designed intracellular robot is shown below. At low Reynolds number as micro (nano) field, the influence of the viscous behavior grows to a large as the size gets small. In nature, bacterial flagella are well known to be able to swim efficiently in liquid. Therefore, the shape of the bacterial flagella is taken as the model of micro-device
Model of nano-machine shaped like bacterial flagella. r[µm]:radius of the agents.
Relationship between size and Force
The relationship between the size scale and the driving force and the resistance force is shown in Fig. 3. The figure means that the efficiency of the swimming flagella gets better as the size of itself is increased.
2.2 CONTROL OF DRIVING AGENTS
In advance, nickel was plated by vacuum vapor deposition on fabricated micro device. Then, the agents can be aligned along the direction of the applied magnetic field. So, the rotating magnetic field can make it to swim with rotary motion.
2.3 INTRODUCE OF THE AGENTS INTO THE CELL
The micro-device is introduced into the cell with the lipofection method. The image is shown in Fig. 4. This method is popular technique as injection of the DNA or some proteins into the cell in biochemical field. After the DNA or proteins covered with lipid layer contact the cell, it is drawn into the cell with the function of cell's endocytosis. In recent years, the research that some micro-structures internalized into the cell instead of DNA is reported.
In order to apply any directional magnetic field, the three pairs of coils were put on the microscope. The photo image of experimental set up is shown in Fig.5, and the calculation formula about generated magnetic field with an air core coil.
Photo image of the experimental setup. Three pairs of coils are put facing each other.
A pair of coils facing each other, as typified by the Helmholtz coils, can generate uniform magnetic field between them. The result of simulation about the magnetic field generated by a pair of air core coils is shown in
Analysis of the magnetic field generated by a pair of coils.
The Density of the magnetic flux of the center of coils is 5 [mT]
3.2 FABRICATION OF THE MICRO-STRUCTURE
In this report, the micro structure was fabricated with C-MEMS technique as a fundamental experiment
Carbon MEMS, describes a manufacturing technique in which carbon devices are made by treating a pre-patterned organic structure to high temperatures in an inert or reducing environment. It has been shown recently that 3D high-aspect-ratio carbon structures can be made from patterned thick SU-8 negative photoresist layers .SU-8 negative photoresist is a high transparency UV photoresist that enables creation of ” structures using traditional UV photolithography. In detail, carbon structures are fabricated by the pyrolysis of photo patterned positive resists and negative photo resists on silicon and fused silica wafers. The pyrolysis process is carried out in a closed ceramic tube furnace in vacuum or a forming gas atmosphere at about 1000 °C. Carbon produced by pyrolysis of photoresist has been extensively characterized by our team.
(a) 2 ml 30 % sucrose solutions were dropped on the glass wafer, and spin coated at 300 rpm for 20 sec. Then, the sacrificial layer was obtained.
(b) 2ml negative photo resist solutions were dropped on the sacrificial layer, and spin coated at 300 rpm for 25 sec and at 4000 rpm for 60 sec. The thickness is about
500 nm. The solutions were mixtures of negative photo resist and its developer as the ratio of 1 to 1.
Complicated components, such as movable parts, are built using a sacrificial layer. For example, a suspended cantilever can be built by depositing and structuring a sacrificial layer, which is then selectively removed at the locations where the future beams must be attached to the substrate. The structural layer is then deposited on top of the polymer and structured to define the beams. Finally, the sacrificial layer is removed to release the beams, using a selective etch process that will not damage the structural layer. There are many possible combinations of structural/sacrificial layer. The combination chosen depends on the process. For example it is important for the structural layer not to be damaged by the process used to remove the sacrificial layer.
© Expose (b) with mask aligner at exposure time 12 sec. The mask patterned in the form of the parallelogram was used in order to encourage the deformation to spiral.
(d) Nickel layer was deposited with the vacuum vapor deposition. Its thickness is about 60 nm.
( e) Release the structure by melting up the sacrifice layer with water.
(f) After replace the structure on the carbon sheet, heat up it to 300°C for I hour and 900°C for 1 hour. Eventually, it is deformation to helix.