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The faster the separation speed, the better the separation resolution ―Nanotechnology makes it possible

  • Read in Japanese
  • 2015/11/12
  • Graduate School of Engineering
  • Assistant Prof. Takao Yasui
  • Associate Prof. Noritada Kaji
  • Prof. Yoshinobu Baba

Prof. Yoshinobu Baba, Associate Prof. Noritada Kaji, and Assistant Prof. Takao Yasui from the Graduate School of Engineering at Nagoya University invented a new separation technology overcoming the conventional separation concept.
All the current separation technologies use a method that involves separation based on differences and interactions between physical or chemical characteristics. In general, the faster the separation speed, the worse is the separation resolution: for the better resolution, the separation speed can be slower. To solve this problem, in this study, the researchers have developed a technology that enables nanopillars (diameter φ500 nm) to pass through in only a particular direction, and improve the separation resolution at faster separation speeds.
This study was published in Nano Letters on April 16, 2015.→Nagoya University Press Release

For faster genome analysis, researchers have updated the development history of nanotechnology. The technology that nobody knows starts from “imagination,” which appears as “interesting phenomena” that nobody knows.

It was in 2003 when the human genome was completely decoded,

―“Why do we need to increase the speed of decoding?”

Approximately 10 years ago, researchers or professionals in the medical field concluded that the analysis speed of genomes in seconds was sufficient, and that analysis in milliseconds was not necessary.


As the decoding process was estimated at a cost of approximately 10 billion dollars per person during that time (ca. 2001), researchers focused on decreasing this cost. Because of their efforts, the decoding process can be performed only at 1,000 dollars at present.


Since then, a brand new target was set for high speed genome analysis, i.e., one-hour-decoding.


Prof. Baba and his research group from the Graduate School of Engineering challenged high speed genome analysis as targets in 2001, thereby anticipating future requirements. Their research results were ahead of their time, and only now this can be regarded as a trending topic in the world.



*******


“The concept of nanopillars did not exist in the real world at that time, but was just an imagined picture by Prof. Baba.”

Associate Prof. Noritada Kaji, as a student in 2001, remembers that Prof. Baba’s innovative ideas impacted many researchers.

A nanopillar is a nano-device that aligns pillar structures of the same nano-size (Figure 1). Prof. Baba suggested that our world would change if DNA could flow through the nanopillars at high speed and separate different sizes of DNA by using semiconductor technology.



Figure 1. Schematic image of nanopillar device (Figure: Kaji et al., Anal. Chem. (2004) 76: 15-22. Copyright (2004) American Chemical Society)



At that time, Prof. Baba and Associate Prof. Kaji (as a student in a master’s program) worked at the Faculty of Pharmaceutical Sciences, Tokushima University. Because of their background, they needed a partner who could provide technical help; therefore, a professor at the University of Tokyo, Emeritus Fellow Yasuhiro Horiike at National Institute for Materials Science (NIMS) was involved in the research.


However, the nanopillar device was not that easy to assemble.

Several students made an attempt, and the first one that was submitted three years later, in 2004, to Associate Prof. Kaji (as a Ph.D. student at that time). Moreover, only two devices materialized, although one proved to be impracticable.


As a Ph.D. student at that time, Associate Prof. Kaji enthusiastically concentrated on the research with the only device in the world, cautiously washed after every experiment (Figure 2).



Figure 2. SEM image of nanopillar structure. The scale bar shows 500 nm. (Figure: Kaji et al., Anal. Chem. (2004) 76: 15-22. Copyright (2004) American Chemical Society)



Finally he succeeded in separating six differently sized DNA molecules in only 680 s, which demonstrated the world’s fastest separation technology at that time, as Prof. Baba expected. (Kaji, et. al., Anal. Chem. (2004) 76: 15-22)


For the further development,

Associate Prof. Kaji visited Emeritus Fellow Horiike at NIMS with Assistant Prof. Takao Yasui (as a student at that time) many times. They learned how to make the nanopillar devices, staying for several weeks at a time. In making a device themselves, they also developed variations, and brushed up their technical ability.


With his original nanopillar devices, Assistant Prof. Yasui (as a student at his master’s course at that time) developed his research theme: the separation principle. He compared the variations of nanopillar device with the one, which Associate Prof. Kaji used.


Consequently, he revealed that, in the zig-zag alignment (as Associate Prof. Kaji’s device), small DNA is sequenced first because big DNA is tumbled by the pillars, whereas in the straight pattern, big DNA is sequenced first (Movie 1). Furthermore, in the straight pattern, the higher the separation speed, the better the separation resolution (Movie 2).



Movie 1. Big and small DNAs passing through the zig-zag alignment of nanopillars (Movie: by courtesy of Prof. Baba)




Movie 2. Big and small DNAs passing through the straight alignment of nanopillars (Movie: Yasui, et al. Nano Lett. (2015) 15: 3445. Copyright (2015) American Chemical Society)



“Imagine—when you are quickly folding washed clothes, your work may be rough.”

Similar to the relationship between efficiency and effectiveness, separation technology, such as filtration and chromatography, usually shows that the higher the separation speed, the worse the separation resolution, while a slower separation speed improves the separation resolution.


Therefore, their technology brought a new phenomenon into separation technology, overcoming the conventional principle of separation.


“However, for the result produced, it is necessary to prove it logically to be approved by the world.”

Assistant Prof. Yasui (as a Ph.D. student at that time) mentioned that when he visited Harvard University in 2008, he learned important tips as a researcher in the nano-technology field. Following the principle of being able to prove something logically, he was faced with the task of explaining the mystery of separation.


The breakthrough was the principle reported by Prof. K. D. Dorfman and his theoretical physicists’ group in 2007, which described a nano-filter by simulation. According to the report, small particles can pass even through corners, and therefore the separation requires a longer time than when using bigger ones. (Laachi, et al., Phys. Rev. Lett. 2007, 98, 098106)


In the case of the nanopillar device, the same principle was demonstrated both by means of calculation and in experiments. When DNA size is small (short), DNA rotates and snakes through the nanopillars. In contrast, big (long) DNA hardly rotates and passes through the nanopillars immediately (Figure 3)



Figure 3. Small DNA requires more time by rotating and snaking through the nanopillars. (Figure: Yasui, et al., Nano Lett. (2015) 15: 3445. Copyright (2015) American Chemical Society)



“We could break the status quo of separation technology, and furthermore, explain the logic.”

Assistant Prof. Yasui remarked that we are now able to take separation technology a step further. Cooperating with other nano-devices, a greater speed of genome analysis will be possible in the near future.


*******


“It started out as a merely academic interest at the university site.”

Prof. Baba, who has successfully cooperated with many industries on a range of projects, emphasizes that basic research at universities as an important partner to the industry.


Technological innovation is possible in developing win–win relationships between universities and industries, like the proven connection between technology and business.


At the beginning of the research, curiosity comes first,

―and then, an opportunity may suddenly present itself for innovation.

(Ayako Umemura)


Researchers featured in this article

Dr. Yoshinobu BabaProfessor, Graduate School of Engineering, Nagoya University

Dr. Baba graduated from the Department of Chemistry, Faculty of Science, Kyushu University, in 1981, and completed his doctorate in 1986. He moved to Oita University in 1986 to work as an assistant professor and lecturer. Then, he became a lecturer and associate professor at Kobe Pharmaceutical University in 1990, and a professor at The University of Tokushima in 1997. Since 2004, he has been a professor at the Graduate School of Engineering, Nagoya University. At the same time, he is a director of the FIRST Research Center for Innovative Nanobiodevices, Nagoya University; a director of Nagoya University Synchrotron Radiation Research Center; a professor at the Institute of Innovation for Future Society, Nagoya University; a professor at the Graduate School of Medicine, Nagoya University; and an advisor at the Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST). His specialties are analytical chemistry and nanobioscience.

Prof. Baba has received many awards during his career:

Merck Award (2004);
Division Award of the Chemical Society of Japan (2008); etc.


***

With comments like “I would like to contribute to a healthy society with nano-technology” Dr. Baba shows where his passion lies. Currently, he works in the field of engineering, but his academic career is not restricted to one field: he graduated in chemistry and worked as a professor in the field of pharmaceutical sciences.
In interviewing him, I am always intrigued to know the thoughts of pioneer. I look forward to further achievements by him and his group (by AU)



Dr. Noritada Kaji Associate Professor, Graduate School of Engineering

Dr. Kaji graduated from the Faculty of Pharmaceutical Sciences, Tokushima University, in 2000, and completed his doctorate in 2004. Between October 2004 and January 2005, Dr. Kaji was awarded a research fellowship (PD), and then started work as an assistant professor at the Graduate School of Engineering, Nagoya University, in February 2005. Since 2012, he was appointed to his current position. At the same time, since April 2015, he is a group leader of JST ERATO Higashiyama Live Holonics Project. His specialties are microdevices and nanodevices, analytical chemistry, and physical pharmaceutical sciences.

Associate Prof. Kaji has received many awards during his career:

The Japan Society of Analytical Chemistry Award (2009);
Royal Society of Chemistry, Physical Chemistry Chemical Physics (PCCP) Award (2008); etc.


***

Dr. Kaji now looks after students as a mentor, which is a key part of his work. His accomplishments in the development of nanopillar devices when he was a student must engender great respect from students.
Because of his cheerful personality, the interview was enjoyable. I would like to come back to interview him again to hear more success stories (by AU)



Dr. Takao Yasui【Assistant Professor, Graduate School of Engineering】

Dr. Yasui graduated from the Department of Chemical and Biological Engineering, School of Engineering, Nagoya University, in 2007. In 2009, he started his research during his doctoral program at the Graduate School of Engineering, Nagoya University, as a Doctoral Course student (DC1) with the Japan Society for the Promotion of Science (JSPS). In 2011, Dr. Yasui obtained his fast-track doctorate in Engineering from Nagoya University, and continued his research as a JSPS postdoctoral fellow. Since 2012, he has been working as an assistant professor at the Graduate School of Engineering, Nagoya University. At the same time, since 2014, Dr. Yasui has been an assistant program manager at the Impulsing Paradigm Change through Disruptive Technologies Program. His specialties are analytical chemistry, nano-materials, and nano-spatial science.

Assistant Prof. Yasui has received many awards during his career:

The 6th Wakashachi Young Scientists' Award (2012);
The 29th Inoue Research Award for Young Scientists (2013);
Young Innovator Award in Chemistry and Micro-Nano Systems (2014); etc.


***

“I enjoy physics,” said Dr. Yasui whose specialty is chemical- and bio-engineering. In this study, physical equations are involved in the paper, and he was pleased with the results.
Dr. Yasui continues to inspire others with his passion for his work. I anticipate further success in his research (by AU)



Links

T. Yasui, N. Kaji, R. Ogawa, S. Hashioka, M. Tokeshi, Y. Horiike, and Y. Baba

Arrangement of a Nanostructure Array To Control Equilibrium and Nonequilibrium Transports of Macromolecules.

Nano Letters 15: 3445 (2015).

(First published on April 16, 2015; doi: 10.1021/acs.nanolett.5b00783)

Noritada Kaji, Yojiro Tezuka, Yuzuru Takamura, Masanori Ueda, Takahiro Nishimoto, Hiroaki Nakanishi, Yasuhiro Horiike, and Yoshinobu Baba

Separation of Long DNA Molecules by Quartz Nanopillar Chips under a Direct Current Electric Field.

Anal. Chem. 76: 15 (2004).
(First published on November 26, 2003; doi: 10.1021/ac030303m)

Nabil Laachi, Carmelo Declet, Christina Matson, and Kevin D. Dorfman

Nonequilibrium Transport of Rigid Macromolecules in Periodically Constricted Geometries.

Phys. Rev. Lett. 98: 098106 (2007).
(First published on March 1, 2007; doi:10.1103/PhysRevLett.98.098106)

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