Summary of Research Project Results Under the JSPS FY2000
"Research for the future Program"



1.Research Institution Nagoya University
 
2.Research Area Integrated Fields
 
3.Research Field Information on Life Systems
 
4.Term of Project FY1996〜FY2000
 
5.Project Number 96I00103
 
6.Title of Project Development of Artificial Cellular Device

7.Projetct Leader
Name Institution,Department Title of Position
Koji, Ikuta Nagoya University, Dept. of Micro System Engineering Professor

8.Core Members

Names Institution,Department Title of Position
Masahiro, Sokabe Nagoya University, Dept. of Cell Biophysics Imaging Physiology Professor
Keiji, Naruse Nagoya University, Dept. of Cell Biophysics Imaging Physiology Associate Professor
Shoji, Maruo Nagoya University, Dept. of Micro System Engineering Assistant Professor

9.Cooperating Researchers

Names Institution,Department Title of Position
Eiji, Suzuki Research Institute of Innovative Technology for the Earth, Catalysis Science Lab. Professor
Toshiaki, Nagakura Suzuka University of Medical Science, Dept. of Medical Electronics Associate Professor
Tadahiro, Hasegawa Nagoya University, Dept. of Micro System Engineering Research Associate

10.Summary of Research Results

New types of micro fluidic device named "Artificial Cellular Device" based on the "Biochemical IC" were developed and basic performances of each chip as well as total ability of combined chips were verified experimentally. The original concept of the biochemical IC has been proposed by the project leader Professor Ikuta. Each biochemical IC chip in a disk shape contains various functional micro compornents such as pumps, valves, concentrators and reactors so on. The biochemical IC introduced the strong point of today's IC/LSI family such as C-MOS/TTL chip-set into biochemistry. Therefore, various kind of micro chemical apparatus can be constructed by the minimum effort of user.
Another important uniqueness is developing 3D (three dimensional) microfabrication process to make a hybrid structure suitable for highly integrated micro fluidic devices. The world's first micro stereo lithography named "IH Process" was developed by Ikuta's group in 1992. From the first generation of IH process with 5 micron resolution, a lot of effort have been made to reach 200 [nm] resolution now. Moreover, movable micro mechanism such as microturbine with shaft was fabricated without any assemble process and it was rotated by laser trapping.
Above micro stereo lithography techniques were utilized to make composite structures consisting of UV polymer and other parts made of various materials. The ultrafiltration membrane to filter various chemicals in the difference of molecular size is inserted during UV polymer solidification process. Since no additional bonding process is necessary, the chip packaging without any leakage was made easily.
In order to verify biochemical reaction, "Lucifarase" (photo protein of firefly) was synthesized from DNA by the cell-free technique in the biochemical IC chips. This is the world's first cell-free protein synthesis in micro chip. These research results opened new era in life science and order-made medicine.

11.Key Words

(1)Artificial Cellular Device、(2)Biochemical IC、(3)Chemical IC
(4)Micro stereolithography、(5)Cell-free Protein Synthesis、(6)Micro Fluidic devices
(7)Signal Transduction in Cells、(8)Artificial Organ、(9)Micro Total Analysis Systems

12.References

[Reference Articles]
Author Title of Article
K. Ikuta, et al. Development of mass productive micro stereo lithography (Mass-IH Process)
Journal Volume Year Pages Concerned
Proc. of IEEE International Workshop on Micro Electro Mechanical System (MEMS96)   1996 301-306

Author Title of Article
K. Ikuta, et al. 3D Micro integrated fluid fystem toward living LSI
Journal Volume Year Pages Concerned
Artificial Life (A-life V), MIT Press   1996 17

Author Title of Article
K. Ikuta, et al. Micro Active Forceps with Optical Fiber Scope for Intra-Ocular Microsurgery
Journal Volume Year Pages Concerned
Proc. of IEEE International Workshop on Micro Electro Mechanical System (MEMS96)   1996 456-461

Author Title of Article
K. Masuda, et al. Noninvasive Measurement of Arteriosclero-tic Index using Brightness Gradient in Time Series Echogramsrecorded by High-frame-rate Echography
Journal Volume Year Pages Concerned
World Cong. on Med. Physics and Biomed. Eng.   1997 711

Author Title of Article
K. Masuda, et al. Noninvasive Preliminary Diagnosis of Myocardial Motion Velocity using High-frame-rate Echography
Journal Volume Year Pages Concerned
Computer Assisted Radiology and Surgery   1997 173

Author Title of Article
S. Maruo, et al. Three-dimensional microfabrication with two-photon absorbed photopolymerization
Journal Volume Year Pages Concerned
Optics Letters 22 1997 132

Author Title of Article
S. Maruo, et al. Two-photon absorbed photopolymerization for three-dimensional microfabrication
Journal Volume Year Pages Concerned
Proceedings of the IEEE International Workshop on Micro Electro Mechanical Systems (MEMS97)   1997 169-175

Author Title of Article
K. Ikuta, et al. Remote Minimal Invasive Surgery Using Hyper Redundant Active Endoscope with Force Sensation
Journal Volume Year Pages Concerned
Proc. of The 3rd International Conference on the Medical Aspects of Telemedicine   1997 97

Author Title of Article
K. Ikuta, et al. Development of Hyper Redundant Active Endoscope for Remote Minimal Invasive Surgery
Journal Volume Year Pages Concerned
Proc. of Computer Assisted Radiology and Surgery (CAR'97)   1997 1044

Author Title of Article
K. Ikuta, et al. Development of Micro Active Forceps with Built-in Fiber Scope for Intra-ocular Microsurgery
Journal Volume Year Pages Concerned
Proc. of the 11th International Symposium and Exhibition on Computer Assisted Radiology and Surgery (CAR'97)   1997 914-919

Author Title of Article
K. Ikuta, et al. New micro stereo lithography for freely movable 3D structure -Super IH process with submicron resolution-
Journal Volume Year Pages Concerned
Proceedings of the IEEE International Workshop on Micro Electro Mechanical Systems (MEMS98)   1998 290-295

Author Title of Article
K. Ikuta, et al. Biochemical IC chip toward cell free DNA protein synthesis
Journal Volume Year Pages Concerned
Proceedings of the IEEE International W orkshop on Micro Electro Mechanical Systems (MEMS98)   1998 131-136

Author Title of Article
S. Maruo, et al. Two-Photon-Absorbed Near-Infrared Photopolymerization for Three-Dimensional Microfabrication
Journal Volume Year Pages Concerned
Journal of Microelectromechanical Systems 7 1998 411-415

Author Title of Article
S. Maruo, et al. New microstereolithography (Super-IH Process) to create 3D freely movable micromechanism without sacrificial layer technique
Journal Volume Year Pages Concerned
Proceedings of the 1998 international symposium on micromechatronics and human science (MHS'98)   1998 115-120

Author Title of Article
K. Ikuta, et al. Chemical IC chip for dynamical control of protein synthesis
Journal Volume Year Pages Concerned
Proceedings of the 1998 international symposium on micromechatronics and human science (MHS'98)   1998 249-254

Author Title of Article
T. Hasegawa, et al. A Control System to Compensate the Hysteresis by Preisach Model on SMA Actuator
Journal Volume Year Pages Concerned
Proceedings of the 1998 international symposium on micromechatronics and human science (MHS'98)   1998 171-176

Author Title of Article
K. Ikuta, et al. Optimum Designed Micro Active Forceps with Built-in Fiberscope for Retinal Microsurgery
Journal Volume Year Pages Concerned
Proc. of First International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI'98)   1998 411-420

Author Title of Article
K. Ikuta, et al. Virtual Endoscope System with Force Sensation
Journal Volume Year Pages Concerned
Medical Image Computing and Computer-Assisted Intervention '98(MICCAI'98)   1998 121-133

Author Title of Article
K. Ikuta, et al. Hyper Redundant Active Endoscope for Minimally Invasive Surgery
Journal Volume Year Pages Concerned
Journal of Robotics Society of Japan 16 1998 145-151

Author Title of Article
K. Ikuta, et al. Minimum Wire Drive of Multi Micro Actuators
Journal Volume Year Pages Concerned
Journal of Robotics Society of Japan 16 1998 791-797

Author Title of Article
K. Ikuta, et al. Micro Concentrator with Opto-sense Micro Reactor for Biochemical IC Chip Family - 3D Composite Structure and Experimental Verification -
Journal Volume Year Pages Concerned
Proceedings of the IEEE International Workshop on Micro Electro Mechanical Systems (MEMS99)   1999 376-381

Author Title of Article
S. Maruo, et al. Two-photon three-dimensional microfabrication for the production of movable mechanism with 0.5 micrometer resolution
Journal Volume Year Pages Concerned
Proc. of 10th International Conference on Solid-State Sensors and Actuators (Transducers'99)   1999 1232-1235

Author Title of Article
K. Ikuta, et al. Biochemical IC family for general micro chemical systems - Development of multiple concentrator, reactor and valve chips
Journal Volume Year Pages Concerned
Proc. of 10th International Conference on Solid-State Sensors and Actuators(Transducers'99)   1999 1046-1049

Author Title of Article
S. Maruo, et al. Pinpoint inner solidification of photopolymerizable resin for three-dimensional microfabrication
Journal Volume Year Pages Concerned
Proc. of Third International Workshop on High Aspect Ratio MicroStructure Technology(HARMST'99)   1999 54-55

Author Title of Article
S. Maruo, et al. Movable microstructures made by two-photon three-dimensional microfabrication
Journal Volume Year Pages Concerned
Proceedings of the 1999 international symposium on micromechatronics and human science(MHS'99)   1999 173-178

Author Title of Article
K. Ikuta, et al. Two-Lead-Wire Drive for Multi-Micro Actuators
Journal Volume Year Pages Concerned
Proc. of the 1999 IEEE Robotics and Automation Conference (ICRA'99)   1999 2378-2384

Author Title of Article
K. Ikuta, et al. General Evaluation Method of Safety for Human-Care Robots
Journal Volume Year Pages Concerned
Proc. of the 1999 IEEE Robotics and Automation Conference (ICRA'99)   1999 2065-2072

Author Title of Article
K. Ikuta, et al. Virtual Endoscope System with Force Sensation
Journal Volume Year Pages Concerned
Proc. of the 1999 IEEE Robotics and Automation Conference (ICRA'99)   1999 1715-1721

Author Title of Article
M. Nokata, et al. Frequency Modulation Velocity Control of Multiple Cybernetic Actuators for Two-lead-wire Drive
Journal Volume Year Pages Concerned
Proc. of 10th International Symposium on Micro Machine and Human Science(MHS'99)   1999 123-128

Author Title of Article
K. Ikuta, et al. Development of Micro Active Forceps with Built-in Fiberscope for Retinal Surgery
Journal Volume Year Pages Concerned
Journal of Robotics Society of Japan 17 1999 1134-1140

Author Title of Article
K. Ikuta, et al. Safety Evaluation Method of Human-Care Robot Control
Journal Volume Year Pages Concerned
Proc. of IEEE 2000 International Symposium on Micro Machine and Human Science(MHS2000)   2000 119-126

Author Title of Article
K. Ikuta, et al. General Evaluation Method for Safety Control of Human-care Robots
Journal Volume Year Pages Concerned
Proceeding of the ASME Dynamic Systems and Control Division 2000 69 2000 1017-1025

Author Title of Article
K. Ikuta, et al. Study on Potable Virtual Endoscope System with Force Sensation
Journal Volume Year Pages Concerned
Medical Image Computing and Computer-Assisted Intervention '00(MICCAI'00)   2000 907-920

Author Title of Article
K. Ikuta, et al. Portable Virtual Endoscope System with Force and Visual Display
Journal Volume Year Pages Concerned
IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS2000)   2000 720-726

Author Title of Article
S. Maruo, et al. Three-dimensional microfabrication by use of single-photon-absorbed polymerization
Journal Volume Year Pages Concerned
Applied Physics Letters 76 2000 2656-2658

Author Title of Article
S. Maruo, et al. Advanced micro stereolithography with multiple UV polymers
Journal Volume Year Pages Concerned
The Transactions of The Institute of Electrical Engineers of Japan 120-E 2000 370-374

Author Title of Article
K. Ikuta, et al. Virtual Endoscope System with Force Sensation
Journal Volume Year Pages Concerned
Journal of Robotics Society of Japan 18 2000 58-65

Author Title of Article
K. Ikuta, et al. General Danger Evaluation Method for Control Strategy of Human-care Robot
Journal Volume Year Pages Concerned
Journal of Robotics Society of Japan 19 2000 81-90

Author Title of Article
K. Ikuta, et al. Fluid drive chips containing multiple pumps and switching valves for biochemical IC chip family-Development of SMA drive 3D micro pumps and valves in leak-free polymer package
Journal Volume Year Pages Concerned
Proceedings of the 13th IEEE International Conference on Micro Electro Mechanical Systems(MEMS 2000)   2000 739-744

Author Title of Article
S. Maruo, et al. Fabrication of freely movable microstructures by using two-photon three-dimensional microfabrication
Journal Volume Year Pages Concerned
Proc. of SPIE 3937 2000 106-112

Author Title of Article
S. Maruo, et al. Unner curable micro stereolithography for movable microstructures
Journal Volume Year Pages Concerned
Proc. of the 8th international conference on rapid prototyping   2000 195-200

Author Title of Article
S. Maruo, et al. Two-photon micro stereolithography with submicron resolution-Fabrication of freely movable mechanism-
Journal Volume Year Pages Concerned
Proc. of the 8th international conference on rapid prototyping   2000 201-206

Author Title of Article
Koji Ikuta, et al. Chemical IC chips using micro stereolithography
Journal Volume Year Pages Concerned
Proc. of the 8th international conference on rapid prototyping   2000 312-317

Author Title of Article
S. Maruo, et al. Optically-driven microstructures fabricated by two-photon microstereolithography
Journal Volume Year Pages Concerned
Proc. of the ASME international mechanical engineering congress and exposition   2000 695-699

Author Title of Article
K. Ikuta, et al. SMA Micro pumps and Switching Valves for Biochemical IC Family
Journal Volume Year Pages Concerned
Proc. of IEEE 2000 International Symposium on Micro Machine and Human Science(MHS2000)   2000 169-174

Author Title of Article
S. Maruo, et al. Multi-polymer microstereolithography for hybrid opto-MEMS
Journal Volume Year Pages Concerned
Proc. of the 14th IEEE International Conference on Micro Electro Mechanical Systems(MEMS 2001)   2001 151-154

Author Title of Article
S. Maruo, et al. Light-driven MEMS made by high-speed two-photon microstereolithography
Journal Volume Year Pages Concerned
Proc. of the 14th IEEE International Conference on Micro Electro Mechanical Systems(MEMS 2001)   2001 594-597

Author Title of Article
K. Ikuta, et al. In-chip cell-free protein synthesis from DNA by using biochemical IC chips
Journal Volume Year Pages Concerned
Proc. of the 14th IEEE International Conference on Micro Electro Mechanical Systems(MEMS 2001)   2001 455-458

Author Title of Article
K. Masuda, et al. Noninvasive Preliminary Diagnosis of Myocardial Motion Velocity using High-frame-rate Echography Computer Assisted Radiology and Surgery
Journal Volume Year Pages Concerned
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Author Title of Article
Koji Ikuta, et al. Micro-stereolithography and its application to biochemical IC chip"
Journal Volume Year Pages Concerned
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Author Title of Article
K. Ikuta, et al. Safety Evaluation method of human-care robot design
Journal Volume Year Pages Concerned
Proc. of 7th International Conference On Rehabilitation Robotics (ICORR'01), in press.   2001  

Author Title of Article
K. Ikuta, et al. Safety Evaluation method of Human-Care Robot Control and Special Robot Simulator
Journal Volume Year Pages Concerned
Proc. of 7th International Conference On Rehabilitation Robotics (ICORR'01), in press.   2001  

Author Title of Article
Koji Ikuta, et al. Mobile Virtual Endoscope System with Haptic and Visual Information for Non-invasive Inspection Training
Journal Volume Year Pages Concerned
Proc. of the 2001 IEEE Robotics and Automation Conference (ICRA'01), in press.   2001  

Author Title of Article
K. Ikuta, et al. General Danger-Evaluation Method of Human-Care Robot Control and Development of Special Simulator
Journal Volume Year Pages Concerned
Proc. of the 2001 IEEE Robotics and Automation Conference (ICRA'01), in press.   2001  

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Cytotechnology 23 1997 55-59

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Cytotechnology 24 1997 135-141

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Cytotechnology 25 1997 17-23

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T. Fujita, et al. Reinforcing apoptosis-resistance of COS, myeloma, and HeLa cells by transfecting with bcl-2 gene
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Cytotechnology 25 1997 25-33

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Shuliang Yao, et al. A Novel Method of High Yield Cell-Free Protein Synthesis
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Journal of Fermentation and Bioengineering 84 1997 548-552

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H. Fukano, et al. Mathematical Model of the amplification Process in Competitive PCR
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Seibutsu-kogaku Kaishi 75 1997 1-8

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S. Terada, et al. Establishing an Apoptosis-Resistant Hybridoma Cell Line for Usage in Serum Starvation Culture
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Kagaku Kogaku Ronbunshu 24 1998 161-164

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You Hui Kim, et al. Establishment of an Apoptosis-Resistant and Growth-Controllable Cell Line by Transfecting with Inducible Antisense c-Jun Gene
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Biotechnology and Bioengneering 58 1998 65-72

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Xin-Chun Shen, et al. Protein Productivity of Cell-Free Translation was Improved by Removing Phosphatase from Wheat Germ Extract with Immunoprecipitation
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Biochemical Engineering Journal 2 1998 23-28

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Biochemical Engineering Journal 3 1999 151-155

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Seibutsu-kogaku Kaishi 77 1999 2-11

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S. YAO, et al. A NEW METHOD FOR MEASURING ATP REGENERATION RATE BY USING A pH METER
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Journal of Bioscience and Bioengineering 87 1999 238-240

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Cytotechnology 31 1999 141-149

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Biochemical Engineering:Marching toward the century of biotechnology   1997 134-137

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Biochemical Engineering:Marching toward the century of biotechnology   1997 806-809

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S. Terada, et al. Effect of cytokines on growth of a mouse hybridoma cell line and its antibody production
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Animal Cell Technology:Basic & Applied Aspect 9 1998 337-342

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Animal Cell Technology:Basic & Applied Aspects 10 1999 171-175

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Proceedings of the fifth Asia-Pacific Biochemical Engineering Conference   1999 15-18

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Keiko Matsuura, et al. Human Amniotic Epithelial (HAE) Cells Express Erythropoietin (Epo) And Epo-Receptor
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Animal Cell Technology:Products from Cells, Cells as Products   1999 521-523

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Animal Cell Technology: Basic & Applied Aspects 11   In press

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M. Sokabe (Bunhitsu) 「Vascular biology Navigator」
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