奈良先端科学技術大学院大学 物質創成科学領域

Staff & Contact

Education and Research Activities in the Laboratory

The Bio-Process Engineering Laboratory promotes developmental research of high-precision and fast manipulation methodologies for small biological materials, utilizing ultra-short pulse laser technology. When an intense femtosecond laser is focused in the vivicinity of a micro-sized biological micro-object in a water medium, an explosion of water is induced at the laser focal point, and shock and stress waves from the explosion act as an impulsive force on the sample (Fig. 1). We have developed several methodologies to manipulate single animal and plant cells utilizing this impulsive force. In addition, this laser manipulation technology has been combined with atomic force microscopes (AFM), microfluidic chip devices, and spectroscopy devices. The AFM is applied to quantify impulsive force and to analyze the sample oscillation induced by that force (Fig. 2). Microfluidic chip devices fabricated by MEMS technology realize sequential high-speed laser manipulation and measuring of biological micro-objects (Fig. 3). Spectroscopy devices are used to identify characteristics of objects manipulated by laser and/or microfluidic chip. Using these techniques, we successfully estimated the adhesion strength between mammalian cells (Ref. 1) and between sub-organelles in plant cells (Ref. 2). Furthermore, we apply such femtosecond laser-induced strong excitation phenomena to photoporation for living vertebrate embryos (Ref. 3) and alga (Ref. 4, Fig. 4) and to induce crystallization (Fig. 5). In an application of microfluidic chip-based cell sorter, we successfully manipulated cells at 100,000/s (World Class) (Ref. 5). These activities and devices aim to open up entirely new areas of life and green innovation. The laboratory fosters human resources with a broad knowledge of engineering and science from areas ranging from physics and chemistry to biology and medicine. Laboratory members are ambitious to pursue a blazing trail in life science and engineering fields.

Research Theme

1. Kinetics of local explosions in water induced by ultrashort laser pulses, and its interaction with biological micro-objects
2. Development of new measurement methods to estimate internal stress in living tissues utilizing ultrashort lasers and atomic force microscopes
3. Development of new cell manipulation techniques in microfluidic chips
4. Exploration of the responsiveness of cells and living tissues to the environment stress and its application to cell manipulation

Explanatory Pictures of Research Activities

Recent Research Papers and Achievements

1. Y.Hosokawa, M.Hagiyama, T.Iino, Y.Murakami, A.Ito, “Noncontact estimation of intercellular breaking force using a femto-second laser impulse quantified by atomic force microscopy,” Proc. Nat’l Acad. Sci. USA, 2011, 108, 1777-1782.
2. K.Oikawa, S.Matsunaga, S.Mano, M.Kondo, K.Yamada, M.Hayashi, T.Kagawa, A.Kadota, W.Sakamoto, S.Higashi, M.Watanabe, T.Mitsui, A.Shigemasa, T.Iino, Y.Hosokawa, M.Nishimura, “Physical interaction between peroxisomes and chloro plasts elucidated by in situ laser analysis,” Nature Plants, 2015, 1, 15035.
3. Y.Hosokawa, H.Ochi, T.Iino, A Hiraoka, M.Tanaka, “Photoporation of biomolecules into single cells in living vertebrate embryos induced by a femtosecond laser amplifier,” PLoS ONE, 2011, 6, e27677.
4. T.Maeno, T.Uzawa, I.Kono, K.Okano, T.Iino, K.Fukita, Y.Oshikawa, T.Ogawa, O.Iwata, T.Ito, K.Suzuki, K.Goda, Y.Hosokawa, “Targeted delivery of fluorogenic peptide aptamers into live microalgae by femtosecond laser photoporation at single-cell resolution,” Sci. Rep., 2018, 8, 8271.
5. T.Iino, K.Okano, S.W.Lee, T.Yamakawa, H.Hagihara, Z.Y.Hong, T.Maeno, Y.Kasai, S.Sakuma, T.Hayakawa, F.Arai, Y.Ozeki, K.Godab, and Y.Hosokawa, “High-speed microparticle isolation unlimited by Poisson statistics,” Lab Chip, 2019,19, 2669- 2677.