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A Controlled-Release Drug Delivery System on a Chip Using Electrolysis

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Pen-Li Huang; Po-Hung Kuo; Yu-Jie Huang; Hsin-Hung Liao; Yao-Joe Joseph Yang; Tao Wang
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Abstract:

A system-on-a-chip (SOC) with integrated drug reservoirs for drug delivery is proposed. Electrolysis is used to generate microbubbles, which are employed as a force to op...Show More

Metadata

Abstract:

A system-on-a-chip (SOC) with integrated drug reservoirs for drug delivery is proposed. Electrolysis is used to generate microbubbles, which are employed as a force to open the reservoirs and release the drug. Wireless components, including an on/off keying receiver, microcontrol unit, regulator, clock divider, and power-on reset, are integrated for remote drug activation. The proposed microchip is fabricated by Taiwan Semiconductor Manufacturing Company 0.35-μm CMOS technology followed by post-IC processing. The total size is 2.48 mm2, and the power consumption is 7.57 mW. The in vitro experiment has proven the feasibility of the proposed drug delivery SOC.
Published in: IEEE Transactions on Industrial Electronics ( Volume: 59, Issue: 3, March 2012)
Page(s): 1578 - 1587
Date of Publication: 20 June 2011

ISSN Information:

DOI: 10.1109/TIE.2011.2160135
Author image of Pen-Li Huang
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Pen-Li Huang was born in Taipei, Taiwan, in 1970. He received the B.S. and M.S. degrees in mechanical engineering from the National Taiwan University of Science and Technology, Taipei, in 1995 and 1999, respectively. He is currently working toward the Ph.D. degree in the Graduate Institute of Electronics Engineering, National Taiwan University, Taipei.
His research interests include microelectromechanical system (MEMS) tec...Show More
Pen-Li Huang was born in Taipei, Taiwan, in 1970. He received the B.S. and M.S. degrees in mechanical engineering from the National Taiwan University of Science and Technology, Taipei, in 1995 and 1999, respectively. He is currently working toward the Ph.D. degree in the Graduate Institute of Electronics Engineering, National Taiwan University, Taipei.
His research interests include microelectromechanical system (MEMS) tec...View more
Author image of Po-Hung Kuo
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Po-Hung Kuo was born in Hsinchu, Taiwan, on July 22, 1984. He received the M.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, with a thesis “ZnO-Based Thin-Film Transistors and Their Applications.” He is currently working toward the Ph.D. degree in electrical engineering at National Taiwan University, Taipei, Taiwan.
His research interests include biosensor design, mixed-mode circuit...Show More
Po-Hung Kuo was born in Hsinchu, Taiwan, on July 22, 1984. He received the M.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, with a thesis “ZnO-Based Thin-Film Transistors and Their Applications.” He is currently working toward the Ph.D. degree in electrical engineering at National Taiwan University, Taipei, Taiwan.
His research interests include biosensor design, mixed-mode circuit...View more
Author image of Yu-Jie Huang
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Yu-Jie Huang received the B.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, in 2006. He is currently working toward the Ph.D. degree in electronic engineering at National Taiwan University, Taipei, Taiwan.
His research interests include CMOS mixed-signal integrated-circuit design and system-on-a-chip design for wireless sensing and biomedical application.
Yu-Jie Huang received the B.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, in 2006. He is currently working toward the Ph.D. degree in electronic engineering at National Taiwan University, Taipei, Taiwan.
His research interests include CMOS mixed-signal integrated-circuit design and system-on-a-chip design for wireless sensing and biomedical application.View more
Author image of Hsin-Hung Liao
Department of Mechanical Engineering, National Taiwan University, Taipei, Taiwan
Hsin-Hung Liao received the B.S. degree in mechanical engineering from National Chung Cheng University, Chiayi, Taiwan, in 2003 and the Ph.D. degree in mechanical engineering from National Taiwan University, Taipei, Taiwan, in 2010.
He is currently with Mechanical Engineering Department, National Taiwan University, Taipei. His research interests include microfluidic devices and optical microsystems.
Hsin-Hung Liao received the B.S. degree in mechanical engineering from National Chung Cheng University, Chiayi, Taiwan, in 2003 and the Ph.D. degree in mechanical engineering from National Taiwan University, Taipei, Taiwan, in 2010.
He is currently with Mechanical Engineering Department, National Taiwan University, Taipei. His research interests include microfluidic devices and optical microsystems.View more
Author image of Yao-Joe Joseph Yang
Department of Mechanical Engineering, National Taiwan University, Taipei, Taiwan
Yao-Joe Joseph Yang (M'01) received the B.S. degree in mechanical engineering from National Taiwan University (NTU), Taipei, Taiwan, in 1990, the M.S. degree in mechanical engineering from the University of California, Los Angeles, in 1995, and the M.S. and Ph.D. degrees in electrical engineering from the Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, in 1997 a...Show More
Yao-Joe Joseph Yang (M'01) received the B.S. degree in mechanical engineering from National Taiwan University (NTU), Taipei, Taiwan, in 1990, the M.S. degree in mechanical engineering from the University of California, Los Angeles, in 1995, and the M.S. and Ph.D. degrees in electrical engineering from the Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, in 1997 a...View more
Author image of Tao Wang
Department of Electronic Engineering, Chang Gung University, Kwei-Shan, Taiwan
Tao Wang was born in Taipei, Taiwan, in 1980. He received the B.S. degree in electronic engineering from Chang Gung University, Kwei-Shan, Taiwan, in 2002 and the M.S. and Ph.D. degrees in electronic engineering from National Taiwan University, Taipei, in 2004 and 2008, respectively.
After one year of national military service from 2008 to 2009, he joined the Graduate Institute of Electronics Engineering, National Taiwan U...Show More
Tao Wang was born in Taipei, Taiwan, in 1980. He received the B.S. degree in electronic engineering from Chang Gung University, Kwei-Shan, Taiwan, in 2002 and the M.S. and Ph.D. degrees in electronic engineering from National Taiwan University, Taipei, in 2004 and 2008, respectively.
After one year of national military service from 2008 to 2009, he joined the Graduate Institute of Electronics Engineering, National Taiwan U...View more
Author image of Yao-Hung Wang
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
Yao-Hung Wang was born in Taiwan. He received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.D. degree from the School of Medicine, National Taiwan University, Taipei, in 1994, and the Master of Internal Medicine degree in neurovascular diseases from University Paris-Sud 11, Paris, France, in 2003.
From 1997 to 2007, he was an Attending Staff Member with the Depart...Show More
Yao-Hung Wang was born in Taiwan. He received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.D. degree from the School of Medicine, National Taiwan University, Taipei, in 1994, and the Master of Internal Medicine degree in neurovascular diseases from University Paris-Sud 11, Paris, France, in 2003.
From 1997 to 2007, he was an Attending Staff Member with the Depart...View more
Author image of Shey-Shi Lu
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Shey-Shi Lu (S'89–M'97–SM'99) received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.S. degree in electrical engineering from Cornell University, Ithaca, NY, in 1988, and the Ph.D. degree in electrical engineering from the University of Minnesota, Minneapolis–St. Paul, in 1991.
During the summer of 1990, he was a Research Aide with the IBM T. J. Watson Research Ce...Show More
Shey-Shi Lu (S'89–M'97–SM'99) received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.S. degree in electrical engineering from Cornell University, Ithaca, NY, in 1988, and the Ph.D. degree in electrical engineering from the University of Minnesota, Minneapolis–St. Paul, in 1991.
During the summer of 1990, he was a Research Aide with the IBM T. J. Watson Research Ce...View more
Contents

I. Introduction

Biomedical electronics that combine the biological and electronic knowledge have made appreciable technological progress in recent years [1]–[3]. For instance, implantable devices for bionic systems based on microchip technologies, such as cochlear [4] and retina [5] implants, have shown remarkable advances in size reductions and system integrity, enabling potential sensation recovery in patients. Furthermore, the use of bioelectronics in neurology and biochemical analysis [6]–[8] is believed to make possible changes in diagnostic and therapeutic behaviors in the next generation. Although the combination of medical devices and electronics has experienced significant breakthroughs, its potential for drug delivery applications remains unrealized.

Author image of Pen-Li Huang
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Pen-Li Huang was born in Taipei, Taiwan, in 1970. He received the B.S. and M.S. degrees in mechanical engineering from the National Taiwan University of Science and Technology, Taipei, in 1995 and 1999, respectively. He is currently working toward the Ph.D. degree in the Graduate Institute of Electronics Engineering, National Taiwan University, Taipei.
His research interests include microelectromechanical system (MEMS) technologies, microwave passive filters, and integrated CMOS MEMS ICs.
Pen-Li Huang was born in Taipei, Taiwan, in 1970. He received the B.S. and M.S. degrees in mechanical engineering from the National Taiwan University of Science and Technology, Taipei, in 1995 and 1999, respectively. He is currently working toward the Ph.D. degree in the Graduate Institute of Electronics Engineering, National Taiwan University, Taipei.
His research interests include microelectromechanical system (MEMS) technologies, microwave passive filters, and integrated CMOS MEMS ICs.View more
Author image of Po-Hung Kuo
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Po-Hung Kuo was born in Hsinchu, Taiwan, on July 22, 1984. He received the M.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, with a thesis “ZnO-Based Thin-Film Transistors and Their Applications.” He is currently working toward the Ph.D. degree in electrical engineering at National Taiwan University, Taipei, Taiwan.
His research interests include biosensor design, mixed-mode circuit design, and biomedical systems.
Po-Hung Kuo was born in Hsinchu, Taiwan, on July 22, 1984. He received the M.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, with a thesis “ZnO-Based Thin-Film Transistors and Their Applications.” He is currently working toward the Ph.D. degree in electrical engineering at National Taiwan University, Taipei, Taiwan.
His research interests include biosensor design, mixed-mode circuit design, and biomedical systems.View more
Author image of Yu-Jie Huang
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Yu-Jie Huang received the B.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, in 2006. He is currently working toward the Ph.D. degree in electronic engineering at National Taiwan University, Taipei, Taiwan.
His research interests include CMOS mixed-signal integrated-circuit design and system-on-a-chip design for wireless sensing and biomedical application.
Yu-Jie Huang received the B.S. degree in electrical engineering from National Cheng Kung University, Tainan, Taiwan, in 2006. He is currently working toward the Ph.D. degree in electronic engineering at National Taiwan University, Taipei, Taiwan.
His research interests include CMOS mixed-signal integrated-circuit design and system-on-a-chip design for wireless sensing and biomedical application.View more
Author image of Hsin-Hung Liao
Department of Mechanical Engineering, National Taiwan University, Taipei, Taiwan
Hsin-Hung Liao received the B.S. degree in mechanical engineering from National Chung Cheng University, Chiayi, Taiwan, in 2003 and the Ph.D. degree in mechanical engineering from National Taiwan University, Taipei, Taiwan, in 2010.
He is currently with Mechanical Engineering Department, National Taiwan University, Taipei. His research interests include microfluidic devices and optical microsystems.
Hsin-Hung Liao received the B.S. degree in mechanical engineering from National Chung Cheng University, Chiayi, Taiwan, in 2003 and the Ph.D. degree in mechanical engineering from National Taiwan University, Taipei, Taiwan, in 2010.
He is currently with Mechanical Engineering Department, National Taiwan University, Taipei. His research interests include microfluidic devices and optical microsystems.View more
Author image of Yao-Joe Joseph Yang
Department of Mechanical Engineering, National Taiwan University, Taipei, Taiwan
Yao-Joe Joseph Yang (M'01) received the B.S. degree in mechanical engineering from National Taiwan University (NTU), Taipei, Taiwan, in 1990, the M.S. degree in mechanical engineering from the University of California, Los Angeles, in 1995, and the M.S. and Ph.D. degrees in electrical engineering from the Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, in 1997 and 1999, respectively.
From 1999 to 2000, he joined the Coventor Inc., Cambridge, as a Senior Application Engineer. Since 2000, he has been with the Mechanical Engineering Department, NTU, where he is currently a Professor and the Deputy Chair. His research interests include microelectromechanical system, nanotechnology, high-precision micromachining, flexible sensing arrays, and sensor networks.
Dr. Yang was the board member of the Chinese Institute of Automation Engineering, where he currently serves as the Secretary General. He was also the recipient of the Outstanding Young Researcher Award (Ta-Yu Wu Memorial Award) of the National Science Council.
Yao-Joe Joseph Yang (M'01) received the B.S. degree in mechanical engineering from National Taiwan University (NTU), Taipei, Taiwan, in 1990, the M.S. degree in mechanical engineering from the University of California, Los Angeles, in 1995, and the M.S. and Ph.D. degrees in electrical engineering from the Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, in 1997 and 1999, respectively.
From 1999 to 2000, he joined the Coventor Inc., Cambridge, as a Senior Application Engineer. Since 2000, he has been with the Mechanical Engineering Department, NTU, where he is currently a Professor and the Deputy Chair. His research interests include microelectromechanical system, nanotechnology, high-precision micromachining, flexible sensing arrays, and sensor networks.
Dr. Yang was the board member of the Chinese Institute of Automation Engineering, where he currently serves as the Secretary General. He was also the recipient of the Outstanding Young Researcher Award (Ta-Yu Wu Memorial Award) of the National Science Council.View more
Author image of Tao Wang
Department of Electronic Engineering, Chang Gung University, Kwei-Shan, Taiwan
Tao Wang was born in Taipei, Taiwan, in 1980. He received the B.S. degree in electronic engineering from Chang Gung University, Kwei-Shan, Taiwan, in 2002 and the M.S. and Ph.D. degrees in electronic engineering from National Taiwan University, Taipei, in 2004 and 2008, respectively.
After one year of national military service from 2008 to 2009, he joined the Graduate Institute of Electronics Engineering, National Taiwan University, as a Postdoctoral Researcher. Since the summer of 2010, he has been with the Electronic Engineering Department, Chang Gung University, where he is currently an Assistant Professor. His research interests include CMOS compatible-micromachining technology, CMOS sensors, RFIC, and biomedical system-on-a-chip.
Tao Wang was born in Taipei, Taiwan, in 1980. He received the B.S. degree in electronic engineering from Chang Gung University, Kwei-Shan, Taiwan, in 2002 and the M.S. and Ph.D. degrees in electronic engineering from National Taiwan University, Taipei, in 2004 and 2008, respectively.
After one year of national military service from 2008 to 2009, he joined the Graduate Institute of Electronics Engineering, National Taiwan University, as a Postdoctoral Researcher. Since the summer of 2010, he has been with the Electronic Engineering Department, Chang Gung University, where he is currently an Assistant Professor. His research interests include CMOS compatible-micromachining technology, CMOS sensors, RFIC, and biomedical system-on-a-chip.View more
Author image of Yao-Hung Wang
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
Yao-Hung Wang was born in Taiwan. He received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.D. degree from the School of Medicine, National Taiwan University, Taipei, in 1994, and the Master of Internal Medicine degree in neurovascular diseases from University Paris-Sud 11, Paris, France, in 2003.
From 1997 to 2007, he was an Attending Staff Member with the Department of Medical Imaging, National Taiwan University Hospital. From 1999 to 2000, he was a Fellow with the Interventional Neuroradiology, Lahey Clinic Medical Center, Burlington, MA. He is currently the Director with the Department of Medical Imaging, Min-Sheng Hospital, Kaohsiung, Taiwan. His current research interests include diagnostic neuroradiology, interventional neuroradiology, computed-tomography-guided biopsy or ganglion block, and percutaneous vertebroplasty.
Yao-Hung Wang was born in Taiwan. He received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.D. degree from the School of Medicine, National Taiwan University, Taipei, in 1994, and the Master of Internal Medicine degree in neurovascular diseases from University Paris-Sud 11, Paris, France, in 2003.
From 1997 to 2007, he was an Attending Staff Member with the Department of Medical Imaging, National Taiwan University Hospital. From 1999 to 2000, he was a Fellow with the Interventional Neuroradiology, Lahey Clinic Medical Center, Burlington, MA. He is currently the Director with the Department of Medical Imaging, Min-Sheng Hospital, Kaohsiung, Taiwan. His current research interests include diagnostic neuroradiology, interventional neuroradiology, computed-tomography-guided biopsy or ganglion block, and percutaneous vertebroplasty.View more
Author image of Shey-Shi Lu
Graduate Institute of Electronics Engineering and Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
Shey-Shi Lu (S'89–M'97–SM'99) received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.S. degree in electrical engineering from Cornell University, Ithaca, NY, in 1988, and the Ph.D. degree in electrical engineering from the University of Minnesota, Minneapolis–St. Paul, in 1991.
During the summer of 1990, he was a Research Aide with the IBM T. J. Watson Research Center, Yorktown Heights, NY, where he was involved with diffusion ohmic contact. Since August 1991, he has been with the Department of Electrical Engineering, National Taiwan University, where he was an Associate Professor and has been a Full Professor since 1995. His current research interests are in the areas of CMOS RFICs and CMOS biotechnology.
Dr. Lu was the recipient of the 2009 Outstanding Research Award of the National Science Council, the 2006 Distinguished Engineering Professor Award of the Chinese Institute of Electrical Engineering, and the 2005 Fu Szu-Nien Award of National Taiwan University.
Shey-Shi Lu (S'89–M'97–SM'99) received the B.S. degree in electrical engineering from National Taiwan University, Taipei, Taiwan, in 1985, the M.S. degree in electrical engineering from Cornell University, Ithaca, NY, in 1988, and the Ph.D. degree in electrical engineering from the University of Minnesota, Minneapolis–St. Paul, in 1991.
During the summer of 1990, he was a Research Aide with the IBM T. J. Watson Research Center, Yorktown Heights, NY, where he was involved with diffusion ohmic contact. Since August 1991, he has been with the Department of Electrical Engineering, National Taiwan University, where he was an Associate Professor and has been a Full Professor since 1995. His current research interests are in the areas of CMOS RFICs and CMOS biotechnology.
Dr. Lu was the recipient of the 2009 Outstanding Research Award of the National Science Council, the 2006 Distinguished Engineering Professor Award of the Chinese Institute of Electrical Engineering, and the 2005 Fu Szu-Nien Award of National Taiwan University.View more
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