Dept. of Mechanical Engineering
Shibaura Insitute of Technology

Biomicrofluidics Lab

(Formerly Cellular Devices Lab)

Functional microfluidic cell culture device for anyone.

The cell culture methods, already established in the 1970s, have been only accessible to researchers or technicians equipped with cell culture rooms exclusively for scientific experiments. But we believe cell culture is too important and fun to limit in a lab. Our goal is to transform cell culture into a handheld game device -- named a "Saibotchi".

About Biomicrofluidics Lab

Mobile long-term cell culture
with reconfigurable microfluidics

The Biomicrofluidics Laboratory at Shibaura Institute of Technology is directed by Associate Professor Nobuyuki Futai of the Department of Mechanical Engineering. Our group creates devices to grow biological cells in better ways (very long-term, 3D culture, co-culture etc.) using reconfigurable microfluidic platforms and on-chip environment control systems.
  We are developing various microfluidic systems for better reconfigurability, easier prototyping, and better cell culture. Such systems include the Braille microfluidic and the machine element-based deformable microchannels. We are also employing a heat-activated passive gas/moisure control inside the microfluidic devices.

Braille microfluidics

Miniature arrays of piezoelectric actuators directly displace elastomeric microchannels and enable perfusing and recirculating liquids with no external supply or tubing.

Discretized channel

Precise rectangular ejector pins arranged in line form a deformed sidewall of a microfluidic channel. Moving the pins enables variable flow rate, handling and patterning cells inside.

On-chip incubation

A nested reservoir with buffer solutions regulates media pH, osmilality, and oxygen levels. We realized a portable cell culture system with various gas atmosphere without a CO2 or multi-gas incubator.

Research

On-chip Multigas Incubation (OCMI)

The cell culture needs a special atmosphere to maintain the physiological conditions of cell culture media. Most microfluidic cell culture devices still require CO2 incubators to adjust the atmosphere. The need of CO2 incubators decreases the effectiveness of the microfluidic cell culture system in terms of the cost, space, and energy, which can be particularly problematic when one wants to vary the gas formulations. We are developing a true-portable system for regulating the environment inside the chip to a CO2 level and humidity (typically 5% CO2 and 95%RH) suitable for cell culture. We have also developed systems for hypoxic and hydrogen-rich culture to stimulate or regulate various cellular functions.

 

Capillary Network On-Chip

Previous microfluidic devices that mimic vasculature or on-chip angio-/vasculogenesis could not generate appropriate flow conditions inside of capillaries, and the duration of cultivation in these devices has been too short to observe long-term remodeling of the capillary networks.  We are developing microfluidic systems for maintaining self-organized microvascular networks on-chip for over a month in a portable microfluidic co-culture system of endothelial cells and fibroblasts. During the cultivations, we observed long-term angioadaptation processes in which excessive vessels got pruned, resulting in a simple flow. The long-term forced pulsatile flow in the vasculatures and the low degradation of pro-angiogenic factors due to low device temperature seem to contribute to the long-term maintenance of the in vitro reconstructed vascular model.

  

Soft-lithographic "Micron"channel for Gradient Generation

Generation of concentration gradients in microfluidic devices is a useful tool for investigating cellular responses. Many of microfluidics-based gradient generators, however, often require complex and/or experienced techniques for microfluidic control to realize stable concentration gradients.
We have developed a silicone-cast microfluidic chip that contains a thin (cross-sectional area 4.4 µm2) microchannel for generation of static concentration gradients of test substances by simple manual liquid handling. A H-shaped thin microfluidic channel terminated by thick channels supported smooth introduction of test substances without producing extra flows that affect the stability of the concentration gradients. Experimental results showed that the developed microfluidic configuration could generate and maintain concentration gradient for at least two days.
 

Reconfigurable Microchannel

We have a novel microfluidic channel in which a sidewall can be adjusted during use. This reconfigurable microchannel enables on-demand adjustment of the channel shape to temporarily create traps and mask culture surface in the microfluidic channel. Flow resistance can be adjusted on demand by narrowing the channel. We succeeded in controlling the flow resistance in the range 10 1–10 5 Pa·s/µL. We also successfully demonstrated on-chip co-culture with in-channel patterning of primary endothelial cells and fibroblasts, long-term culture in a variable culture area, and co-culture of spheroids with migration assay. This reconfigurable microfluidic channel can also generate displacement flow in situ, providing a foundation for flexible microfluidic systems that can handle a wide range of biofluids, solids, and even gases.
   

Portable Cell Device with Skin

Cultured cells seem to require many kinds of special treatment -- constant temperature, exchange of media with nutrients and growth factors, elevated humidity, and even antibiotics. This is rather surprising given that  we, made of cells, do not require any of them. We are interested in what create the difference in self-sustainability between cultured cells and animals. We are focusing on the protective functions and media conditioning functions of skin cells and we are developing a culture device that is covered with a skin as a barrier that does not obstruct mass transfer. So far, we have succeeded in co-culturing cells with a 3D skin equivalent outside of a CO2 incubator.
 

On-chip Cryopreserved Cell Culture Device

Cryopreservation of cells on microfluidic devices that enables long-term shipping and storage is still challenging. We developed a versatile microfluidic channel that allows the whole cell cryopreservation processes from freezing to restarting culture therein. The polydimethylsiloxane (PDMS)-made microchannel has two wells with smooth walls, and the flow rates can be switched using either Laplace pressure- or hydrostatic pressure-driven flow. We confirmed that cells introduced into the microchannel were successfully collected at the bottom of the well by way of Laplace pressure-driven flow. Meanwhile, we simultaneously achieved the replacement of cryopreservation medium to growth medium after thawing and the transferring of the cells to another well for restart culture  using hydrostatic pressure. Viability of restarted culture of cells cryopreserved in the microfluidic channel was also confirmed. The cells became near confluent three days after thawing the microfluidic device.
  

Publications

2018

N. Futai, K.Fujita, W.Ikuta, "Reconfigurable Microfluidic Channel with Pin-discretized Sidewalls," J. Vis. Exp., in press.

2017

N. Futai, T. Sano,M. Sumita, A. Takano, R. Yokokawa, T. Miura, "Vascular Remodeling Processes In An Integrated Microfluidic Device," in 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS2017), Savannah, GA, USA, 2017.

T. Miura, N. Futai, D. Sasaki, Y. Nashimoto, R. Yokokawa, K. Yamamoto, S. Koide, "Remodeling in synthetic vascular network - experiment and modeling," in 18th International Congress on Developmental Biology  (ISDB2017), Singapore, 2017.

M. Oono, K. Yamaguchi, A. Rasyid, A. Takano, M. Tanaka, N. Futai, "Reconfigurable Microfluidic Device with Discretized Sidewall," Biomicrofluidics, vol. 11, 034103, May 2017.

2016

A. Takano, H. Nakashima, A. D. F. T. Fernandes, M. Tanaka, N. Futai, "On-Chip Cryopreservation for Microfluidic Cell Culture," Cryobiology and Cryotechnology, vol. 62, pp. 115-118, 2016.

N. Futai, S. Maeda,A. Takano, A. Nakamasu, Y. Nashimoto, R. Yokokawa, T. Miura, "Microfluidic model of long-term vascular remodeling processes," 24th Annual Meeting of the Japanese Vascular Biology and Medicine Organization, Nagasaki, Japan, Dec. 2016.

M. Oono, A. Takano,N. Futai, "Reconfigurable Microfluidic Channel Capable of Patterning of Cells," 29th International Microprocesses and Nanotechnology Conference (MNC2016), Kyoto, Japan, Nov. 2016.

M. Tamura, Y. Shiota, A. Yoshino, T. Ogawa, A. Takano,N. Futai, "Evaluation of the Diffusion Progress in the Microfluidic Static Gradient Generator," 29th International Microprocesses and Nanotechnology Conference (MNC2016), Kyoto, Japan, Nov. 2016.

S. Maeda, A. Takano,A. Nakamasu, R. Yokokawa, T. Miura, N. Futai, "Long-term Perfusion Culture Model of 3D Microvascular Remodeling,"  29th International Microprocesses and Nanotechnology Conference (MNC2016), Kyoto, Japan, Nov. 2016.

M. Tamura, T. Ogawa, A. Takano,N. Futai, "A Microfluidic Static Gradient Generator Using for Axonal Biology," 8th International Symposium on Microchemistry and Microsystems (ISMM2016), Hong Kong, May 2016.

M. Tozawa, M. Tamura, A. Takano, N. Futai, "Concentration gradient generation device for axon separation and guidance," 28th Japan Soc. Mech. Eng. Bioengineering Conference, Tokyo, Japan, Jan. 2016.

2015

K. Niikura, S. Shimaura, S. Maeda, A. Takano, A. Nakamasu, R. Yokokawa, T. Miura, N. Futai, "Microfluidic Recirculation System for On-chip 3D Capillary Network Formation,"  32nd Society for Chemistry and Micro-nano Systems (32nd CHEMINAS), Fukuoka, Japan, Nov. 2015.

M. Oono, T. Yamanaka, A. Takano, N. Futai, "Reconfigurable Microchannel for Cell Cultures," Biomedical Engineering Conference 2016, Okayama, Japan, Sep. 2015.

S. Chikazawa, A. Takano, S. Hirano, R. Kurokawa, X. Lee, N. Futai, "Hydrogen-rich Atmosphere in On-chip Cell Culture device," Biomedical Engineering Conference 2016, Okayama, Japan, Sep. 2015.

Y. Ashino, H. Nakashima, A. Takano, N. Futai, "Cryopreservation of Microfluidic Device for Cell Culture," Biomedical Engineering Conference 2016, Okayama, Japan, Sep. 2015.

2014

A. Takano, M. Tanaka, and N. Futai, "On-chip multi-gas incubation for microfluidic cell cultures under hypoxia," Biomicrofluidics, vol. 8, 061101, Nov 2014.

M. Tamura, S. Maeda, T. Ogawa, M. Tanaka, N. Futai, "A microfluidic static gradient generator using limited diffusuon through T-shaped narrow channels," in Micro-NanoMechatronics and Human Science (MHS), 2014 International Symposium on, Nagoya, Japan, Oct. 2014.

M. Oono, K. Mikami, N. Futai, "Leakage-free reconfigurable microchannel having moving sidewalls sealed with hydrocarbon sealant and oil seals," in Micro-NanoMechatronics and Human Science (MHS), 2014 International Symposium on, Nagoya, Japan, 2014.

A. R. Dixon, S. Rajan, C. H. Kuo, T. Bersano, R. Wold, N. Futai, S. Takayama, G. Mehta, "Microfluidic device capable of medium recirculation for non-adherent cell culture," Biomicrofluidics, vol. 8, 016503, Jan 2014.

2013

A. Takano, T. Kon, Y. Furuya, K. Mochitate, M. Tanaka, N. Futai, "Microfluidic long-term cell culture platform with cell-cell interaction monitoring using surface acoustic wave," in Micro-NanoMechatronics and Human Science (MHS), 2013 International Symposium on, Nagoya, Japan, 2013.

A. Takano, S. Inomata, M. Tanaka, N. Futai, "Microfluidic Culture of Primary Neurons with On-chip Hypoxic Conditioning," in 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS2013), Freiburg, Germany, 2013.

T. Ogawa, N. Matsunaga, S. Inomata, M. Tanaka, N. Futai, "A simple microfluidic gradient generator with a soft-lithographically prototyped, high-aspect-ratio, ~2 microm wide microchannel," Conf Proc IEEE Eng Med Biol Soc, vol. 2013, pp. 5521-4, 2013.

~2012

A. Takano, M. Tanaka, N. Futai, "On-chip CO2 incubation for pocket-sized microfluidic cell culture," Microfluid. Nanofluid., vol. 12, pp. 907-915, 2012.

N. Matsunaga, S. Inomata, T. Ogawa, A. Takano, M. Tanaka, N. Futai, "An Braille-driven mixed extended-nano- and microfluidic chip," presented at the 25th Society for Chemistry and Micro-Nano Systems (25th CHEMINAS), Kumamoto, 2012.

A. Takano, T. Ogawa, M. Tanaka, N. Futai, "On-chip incubation system for long-term microfluidic cell culture," Conf Proc IEEE Eng Med Biol Soc, vol. 2011, pp. 8404-7, 2011.

T. Ogawa, A. Takano, M. Tanaka, N. Futai, "Softlithographic Prototyping Method of Extended-Nanochannels," in 11th Intl. Symp. Micro-Chemistry & Microsystems (ISMM2011), Seoul, Korea, 2011.

N. Futai, "Reconfigurable Microchannels with Discretized Moving Sidewalls," Chem Micro-Nano Syst, vol. 10, pp. 24-25, 2011.

Y. C. Tung, Y. S. Torisawa, N. Futai, S. Takayama, "Small volume low mechanical stress cytometry using computer-controlled Braille display microfluidics," Lab Chip, vol. 7, pp. 1497-503, Nov 2007.

B. H. Chueh, D. Huh, C. R. Kyrtsos, T. Houssin, N. Futai, S. Takayama, "Leakage-free bonding of porous membranes into layered microfluidic array systems," Anal. Chem., vol. 79, pp. 3504-8, May 1 2007.

N. Futai, W. Gu, J. W. Song, S. Takayama, "Handheld recirculation system and customized media for microfluidic cell culture," Lab Chip, vol. 6, pp. 149-54, Jan 2006.

W. Gu, X. Y. Zhu, N. Futai, B. S. Cho, S. Takayama, "Computerized microfluidic cell culture using elastomeric channels and Braille displays," Proc. Natl. Acad. Sci., vol. 101, pp. 15861-15866, Nov 2004.

N. Futai, W. Gu, S. Takayama, "Rapid Prototyping of Microstructures with Bell-Shaped Cross-Sections and Its Application to Deformation-Based Microfluidic Valves," Adv Mater, vol. 16, pp. 1320-1323, 2004.

N. Futai, K. Matsumoto, I. Shimoyama, "A flexible micromachined planar spiral inductor for use as an artificial tactile mechanoreceptor," Sensors and Actuators A: Physical, vol. 111, pp. 293-303, 2004.

N. Futai, K. Matsumoto, I. Shimoyama, "Fabrication of high-aspect-ratio PZT thick film structure using sol-gel technique and SU-8 photoresist," in Micro Electro Mechanical Systems, 2002. The Fifteenth IEEE International Conference on, 2002, pp. 168-171.

People

PI

Nobuyuki Futai: Associate Professor, Department of Mechanical Engineering

Current Students

Tomohiro Sekiguchi (2018 M1)
Makoto Torii, Hikaru Takamiyagi, Kenji Fujita, Tatsuya Horiuchi, Ryoma Saito, Masahiro Sumita, Yuki Arai, Wataru Ikuta, Yuta Yatsuka (2017 B4).

 

Members ~2016

Atsushi Takano: Postdoc
Makoto Tamura, Shugo Maeda, Masahiro Oono : Graduate students
Rasyid, Makoto Nagata, Daisuke Fukai, Yohei Shiota, Go Kuroiwa, Masashi Kajino, Keisuke Yamaguchi, Misaki Watanabe, Zafira, Akihisa Yoshino : Undergraduate students

Access

 
Biomicrofluidics Lab is located on the 3rd floor, in the southwest leg of the arch-shaped Research Building. It is right above the entrance in the southwest leg of the archway(2nd Floor).

PI Office

Nobuyuki Futai Laboratory
03F32a Research Building
Department of Mechanical Engineering
College of Engineering
Shibaura Institute of Technology
3-7-5 Toyosu, Koto-ku, Tokyo 135-8548 JAPAN.
 

Biomicrofluidics Lab

Biomicrofluidics Laboratory
03C29 Research Building
Department of Mechanical Engineering
College of Engineering
Shibaura Institute of Technology
3-7-5 Toyosu, Koto-ku, Tokyo 135-8548 JAPAN.
 

Contact