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Say Goodbye to Pain and Disease
NTU Interdisciplinary Research Group Developed Biomedical Chip

Can you imagine for a second, that in the near future, all you need is your cell phone, and you will get hold of your physical conditions at all times, even cure your diseases and pain!! With the "biomedical chip" developed by NTU's research group, this is no longer a far-fetched fantasy.

In recent years, "biomedical chips", which are the products of the combination of microelectronics, micro-machinery, life sciences and bio-information, has become one of the most popular research areas in science and technology. According to estimates, the global market for biomedical semiconductors will reach 4.6 billion in the year 2012 and become an impetus for industrial growth. The world's largest IC design company—Qualcomm, has invested considerable amount of R&D resources into developing bio-medical chips owing to the chips' great future potentials.

To successfully develop a bio-medical chip, one must possess proficiencies in IC design, MEMS technology and bio-medical knowledge. Consequently, cross-interdisciplinary integration is often the most critical and the most difficult point. The research team led by Dr. Shey-Shi Lu, Director of the Graduate Institute of Electronics Engineering, engaged in cross-disciplinary cooperation with the College of Engineering, the College of Medicine and NTU Hospital over the past several years and has successfully developed different kinds of bio-medical chips. So far the team members have three papers published in the Hall of Fame of international IC design—the ISSCC, and their outstanding achievements have been widely reported by both international and domestic media. In fact, Dr. Lu's team is the only group of scholars from Taiwan that have the greatest number of papers published in ISSCC. Here we shall introduce three major research achievements.

-The world's first wireless protein detection chip-
Wireless C-reactive protein sensor

Cardiovascular diseases have become the number one killer in many advanced countries. Therefore, if we could diagnose and treat this kind of diseases instantly, we will be able to prevent many tragedies. In recent years we have discovered that the density of C-reactive protein (CRP, a clinical marker of inflammation) in the blood is closely related to cardiovascular diseases and can serve as an indicator. However, the traditional CRP detection machine is too bulky and takes too long, and does not conduce to real time monitoring.

In order to miniaturize CRP testing, Professor Shey-shi Lu of the Institute of Electronics Engineering, Professor Long Sun Huang of the Institute of Applied Mechanics, and Doctor Nai Kuan Chou of NTU Hospital engaged in cross disciplinary cooperation. They were able to conquer the barriers between wireless technology and bio-medical sensing technology and develop a c-reactive protein wireless sensor the size of a grain of rice which utilized CMOS-compatible MEMS technology to integrate CRP micro-cantilever sensor and wireless bio-medical system on chip (SoC) to transmit the density signals wirelessly to a personal computer or PDA (see Figure 1). Thus, a small sized, low-cost, and real time CRP detection method was successfully developed. This was the first bio-medical related paper published in ISSCC, and the first wireless protein detecting wireless chip in the world.

-Implantable CMOS drug delivery system on chip (SoC)-

Even though we have the ability to sense our physiological information and detect the diseases, when we face sudden illness like cardiovascular diseases, if we cannot give them first time treatment, we are likely to end up with irreparable regrets. The traditional method of taking medicine or taking injections, usually requires that the medicine pass through the body's circulatory system before it reaches the affected part, or requires the presence of professional medical personnel, so often the prime time for effective treatment is lost.

In view of this, Professor Shey-shi Lu of the Institute of Electronics Engineering, Professor Yao-Joe Joseph Yang of the Department of Mechanical Engineering, Professor Chii-Wann Lin of the Institute of Biomedical Engineering and Dr. Yao-Hung Wang of NTU Hospital cooperated to develop the world's first CMOS drug delivery system on chip (SoC), which could be transplanted into the human body to deliver drugs, and enhance the treatment effect through sophisticated control. This implantable CMOS chip brings together a number of wireless control and driving circuitry, and a drug delivery array, which can release drugs like nonapeptide, leuprolide, acetate, and nitroglycerin, which can be applied to local diagnosis or treatment, or for the immediate relief of heart disease. This micro-system can be implanted into the human body through minimal surgery, and the wireless function which it possesses allows medical staff to conduct non-invasive real time treatment on patients. This system on chip can provide solutions that are better than the existing technologies in terms of size, cost, and power conditions. Produced by standard 0.35 micron CMOS process, the surface area of the chip is only 1.77mm x 1.4mm. This research achievement was considered as the 2009 solicited invitation paper for ISSCC, and was published in February of 2009. When published, it attracted the attention of EE Times of America which used the title "Implantable Drug Delivery SoC Shows Promise" to cover the story.

-CMOS implantable single chip pain stopping system-

Electrical nerve stimulation therapy has been proved to have positive effect on more than twenty kinds of neurological disorders with reversible security, and pulse radio frequency (PRF) electrical stimulation is a new method in interventional pain therapy which primarily uses pulse radio frequency electrical stimulation to stimulate the nerve conduction path neutrons to achieve the purpose of effectively blocking the pain, and the patients will not lose other movement capabilities because of this.

But at present, clinically one therapy process can only be effective for three to six months, after which the feeling of pain will gradually resume, so patients must repeat the same therapy process again and again, but the electrodes can only be used once and are quite expensive, resulting in medical burden.

Therefore, Professor Shey-shi Lu of the Institute of Electronics Engineering and Professor Chii-Wann Lin of the Institute of Biomedical Engineering integrated the clinically used pulse radio frequency electrical stimulation method to stimulate the dorsal root ganglion (DRG) which is responsible for transmitting pains. They developed a miniature implantable pain-stopping CMOS system on chip which is small-sized, battery free and low cost, low powered (3.3V) and can be used repeatedly and tested it on mice. When the external radio frequency source approaches the mouse, the blue LED light inside the body of the mouse will light up, indicating that the power source has been successfully coupled with the chip inside the mouse. When this pain-stopping chip receives the wireless power source from outside, pulse radio frequency will be created to stimulate the dorsal root ganglion of the mouse, thereby achieving the function of stopping the pain. If we divide the mice into the experiment group and the control group, we shall find that the mice which were implanted with the chip feel less pain, as shown in the above Von Frey (VF) pain value index chart. This research has been published in this year's ISSCC and received broad affirmation from domestic and international media.

These biomedical chip technologies are still being tested in the laboratories, but before long, they will officially enter our daily lives, and change our medical habits greatly. In essence, they will improve the living quality of the patients.

Chinese version