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HOME > No.11, Dec 2017 > Feature Story :How Capturing the Movement of Ions can Contribute to Brain Science and Improve Disease Diagnosis

How Capturing the Movement of Ions can Contribute to Brain Science and Improve Disease Diagnosis

Kazuaki Sawada

Professor Kazuaki Sawada’s work focuses on the development of biosensors that combine integrated circuit technology and sensor technology. Currently Prof. Sawada’s main project is working on a "bio image sensor", which he hopes to use to directly observe ion distribution and movement as visual images, in order to contribute to the development of brain science and disease diagnosis. There is growing excitement in the scientific community regarding the potential practical applications of this innovative sensor, which Prof. Sawada is striving to fulfill by establishing research associations and incorporated associations through industry-university.

Interview and report by Madoka Tainaka

Development of world's first sensor that can detect ion reactions

Today, the major types of image sensors for acquiring two-dimensional images by sensing are CCD (Charge-Coupled Device) and CMOS (Complementary metal-oxide-semiconductor). These semiconductor devices are mounted on digital cameras and smartphone cameras. They capture the amount of light as an amount of electric charge and process it after converting it to an electric signal and are widely used not only for cameras but also for measurement of magnetic fields and voltages. However, until now, there were no sensors that could directly capture the distribution and movement of ions, in the way that Prof. Sawada’s bio image sensor is now able to do.

"As a means for measuring ions, using litmus paper for measuring hydrogen ions is well established, but what sets our device apart is that it can measure the amount. This is the world’s first sensor that can directly observe the movement of ions," says Prof. Sawada.

The trigger for development dates back to Prof. Sawada’s fourth undergraduate year when he was a student at Toyohashi University of Technology. In response to a request from a company, he worked on the development of a hydrogen ion sensor through an industry-university collaboration that became his graduation thesis. However, the sensor didn’t achieve the desired performance and the research ended there. After that, Prof. Sawada worked for a time on material development, but after doing some research on image sensors at Shizuoka University more than ten years later, he decided to once again take on the challenge of becoming the first person to successfully image ion changes.

"As a mechanism, we read the movement of ions from the change in potential of a semiconductor (ISFET: Ion Sensitive Field Effect Transistor) by means of a sensitive membrane of ions placed on the surface of the semiconductor. It’s a little complicated, but at that time, depending on the concentration of hydrogen ions, a state called a "potential well" in quantum theory is formed on the semiconductor surface. To put it simply, the depth of the cup changes according to the concentration of ions. To measure the depth of the cup, we inject a lot of electric charge into it and measure the amount of charge that accumulates. We can then measure the electric charge by converting it into a voltage like a CCD or CMOS image sensor. In this way, we can read the ion concentration with a high level of sensitivity," explains Prof. Sawada.

In 1997, Prof. Sawada acquired a patent for this innovative method, and since then has continually strived to further develop and improve the bio image sensor.

As the accuracy improved we became aware of the potential goals

Unfortunately it was not possible to achieve the target accuracy straight away. "At the beginning of the development, the number of pixels was just 1×8, and by 2005 we achieved 10×10, but at this level we could just about sense the change in ions when we dropped orange juice on the sample. At this level, nobody was really interested. However, at a scientific meeting in 2007, when we increased the number of pixels to 32×32 and used the sensor to show rice roots emitting citric acid, everyone got excited. There was a theory that plant roots emitted citric acid and dissolved nutrients in the soil to absorb them, but until then no one had been able to observe the phenomenon. After that breakthrough, researchers in various fields came to me saying they wanted to use the sensor."

Originally, the research started from the pure interest of Prof. Sawada, who wanted to try to simply observe the movement of ions. But based on people’s reactions, he began to understand how the research would be useful for society. "Doctors at the medical department told me that the ability to see ion reactions could be revolutionary in medicine. I was surprised when people told me it was so groundbreaking. So, when I brought them a prototype that I had managed to make, they were unsatisfied, explaining that they needed at least 100 pieces. If we do not raise the accuracy and usability to a level that has the impact of making potential users want to use the technology, it will not become widely used. This revelation changed the philosophy of my research. Since then, my goal has been to fulfill my responsibility to contribute to society, whether or not the research can be published as a paper."

After that, in 2011, Prof. Sawada succeeded in observing the release of acetylcholine from a rat cerebral cortex without labels with a 128×128 (16,000 pixels) element. Furthermore, in 2014, he observed the release of potassium ions by stimulating a rat hippocampus with glutamic acid.
"Usually, a wet sample will break as soon as you place it on a chip. That was the tricky part, which explains why it took time to develop the initial idea. However, by enhancing the waterproofing of the chips, we made it possible to capture the appearance of ions leaking out of a cell, which no one had ever seen before. With these unprecedented tools that enable us to look at cells from the outside, we anticipate the potential for creating new academic fields."


In addition to that, Prof. Sawada is also working on research such as the development of a sensor that separates excitation light and fluorescent light. The key point is that it does so without using the kind of expensive optical filter that is usually indispensable for fluorescence microscopy. What is more, it can visualize the fluorescence of samples with the same accuracy as a fluorescence microscope. As a result of such discoveries, Prof. Sawada explains that he receives endless daily inquiries from companies and research institutions, especially from the medical field.

Promoting social implementation through two pillars: the study group and the council

At present, the number of pixels of the element of the bio image sensor has reached 1.3 million (1280×960). This has been achieved through industry-university collaborative development. In order to advance implementation in society, in 2012, Prof. Sawada established the "Multimodal Bio Image Sensor Study Group", of which he is the chairman. About 25 organizations including companies such as semiconductor manufacturers, universities, and national research institutions have participated and are deepening consideration of the industrial contribution of multimodal bio image sensors and the creation of new businesses.

Meanwhile, in September 2016, Prof. Sawada founded a general incorporated association named "Toyohashi Sensor Council". The council is accelerating initiatives to create bio sensor markets, such as determining standards and specifications, holding technical lectures and providing consultancy.
"Since our research group is after all a university organization, there were aspects that were difficult to control from the perspective of fairness, such as how to handle patents in promoting commercialization. So I decided to devote myself to research and transferred the license of approximately 70 patents owned by the university to the council, and we made the council responsible for its development as a business," says Prof. Sawada.

Incidentally, since the press release, more and more people are asking to participate in the council, but Prof. Sawada says not everyone can join.
"Since our goal is not to make money, but to return the intellectual property of the university to society and to maximize the social utility of the sensor, I select companies to participate based on their willingness to get involved on a volunteer basis. We’re expecting to be able to announce a new product next year, so hopefully that’s something we can all look forward to."

It is indeed exciting to have such innovative achievements on the horizon, especially when they are the product of a researcher’s simple passion to know the unknown, and to be of service to society.

Reporter's Note

Prof. Sawada's goal to become a researcher started from his love of Antarctica. "I wanted to join the Japanese Antarctic Research Expedition, but I didn’t feel I could become a geologist or meteorologist. However, I thought that I might be able to work in communications, so I joined the engineering department. Actually, I joined the new Department of Electrical and Electronic Information Engineering. In the end, I did not study communications at all, and my teacher advised me that sensors will become important in various fields in future, so I proceeded down the road of sensor development," says Prof. Sawada.

Although Prof. Sawada says he has "completely moved on from his early goal," he has not thrown away his dream of traveling to Antarctica. "Sensors should be indispensable for measuring ice sheets and soil. I would like to see this unknown world that nobody has seen yet. I would be delighted to go if I was asked," he laughs. In this way, Prof. Sawada shows himself to be a researcher who is driven by curiosity and who purely wants to explore the truth.

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Researcher Profile

Dr. Kazuaki Sawada

Dr. Kazuaki Sawada

Dr. Kazuaki Sawada received his B.A. and M.S. degrees in electrical and electronic engineering in 1986, 1988, respectively, and he received a Ph.D. degree in system and information engineering in 1991, all from Toyohashi University of Technology, Aichi, Japan.
From 1991 to 1998, he was a Research Associate in the Research Institute of Electronics, Shizuoka University, Shizuoka, Japan. Since 1998, he joined the Department of Electrical and Electronic Engineering, Toyohashi University of Technology, where he is now serving as a Full Professor.

Reporter Profile

Madoka Tainaka

Madoka Tainaka is a freelance editor, writer and interpreter. She graduated in Law from Chuo University, Japan. She served as a chief editor of “Nature Interface” magazine, a committee for the promotion of Information and Science Technology at MEXT (Ministry of Education, Culture, Sports, Science and Technology).