Biocompatible Ultra-Thin Polymer Films:
A Mass Production Technology toRevolutionize the Medical Field

Micro/Nano Technology Center, Tokai University
www.mnc.u-tokai.ac.jp

Films used in industry today can be as thin as one
micrometer, but in the near future, it is likely thatthese will be as thin as a few tens of nanometers. As
such, at least one research center is already using
web handling theory and roll-to-roll equipment todevelop and utilize such films. Established to bring
together up-and-coming researchers from a myriadof fields, the interdisciplinary Micro/Nano TechnologyCenter (MNTC) at Japan's Tokai University is working
to develop ultra-thin polymer films with thicknesses
under 100 nm, as well as to search out potential applications. We spoke to Professor Rio Kita of the Department of Physics, School of Science; Associate
Professor Yosuke Okamura of the Department of Applied Chemistry; and Tokai University Department ofMechanical Engineering Junior Associate Professor
Yuta Sunami about their research in this field.

Targeting Medical Applications

From Left, Junior Associate Professor Yuta Sunami,
Professor Rio Kita, and Associate Professor YosukeOkamuraand medical schools have come together to work at MNTC
with the common goal of developing next-generation medical

Consisting of eight campuses throughout Japan, Tokai Uni-technologies using ultra-thin polymer films, a theme that allows

versity is one of the largest educational systems in the coun-each member to apply his or her individual field of specialty.

try. MNTC was established at the Shonan campus, locatedProfessor Rio Kita, Department of Physics, is an expert in poly-in Kanagawa prefecture, in January 2015. A comprehensive

mers and leads the MNTC research team.

subsidy was provided by the Ministry of Education, Culture,

Under the concepts of “Create,” “Test,” and “Know,” theSports, Science and Technology (MEXT)—the MEXT-support-members have divided themselves into three sub-groups.

ed Program for the Strategic Research Foundation at Private

Associate Professor Okamura of the Department of Applied

Universities, a subsidy for supporting various research proj-

Physics and Junior Associate Professor Sunami of the De-ects at private universities. MNTC covers a total floor area ofpartment of Mechanical Engineering belong to the “Create”

403.57 m2 and is equipped with all of the advanced researchgroup. Dr. Okamura is in charge of design and production, andfacilities, including a clean room, a cell culture lab, a chemistry

Junior Associate Professor Sunami is in charge of develop-lab, and a constant temperature/humidity room.

ing the roll-to-roll production process with an eye on eventual

Eight young researchers from the engineering, physics,

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mass-production. Ultra-thin polymer film, in short, is any planar

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September / October 2016

structure of under 100 nm in thickness that can stand without
any support (free-standing). Such thin-films are often referred

PVA

SiO2PVASpin Coat
4,000 rpm, 20 s

to as nano-sheets.
The major characteristic of these films is that they are pla-PLLAnar (two-dimensional). This planar nature provides the films

Spin Coat
4,000 rpm, 20 swith excellent flexibility. They also have the ability to adhere
easily to all types of uneven structures. In other words, theyPLLA

have contact adsorption and thus have the ability to adhere(anchor) extremely well to both flat and curved surfaces. As
such, the films do not require any adhesives and can adhere
to wet surfaces. As a member of Professor Shinji Takeoka’s
research team at Waseda University’s School of Advanced
Science and Engineering, Associate Professor Okamura de-PLLA Ultra-thinPolymer Film

Immerse in Waterto Release From
PVA Layer

Conventional Ultra-thin Polymer Film Forming Processveloped unique nano-materials, which he has continued to

Coating Arm

develop under a different direction at MNTC. Currently, he isworking to create an ultra-thin polymer film from highly bio-Filmcompatible materials, with one major goal being to use thesefilms inside the human body.
MICROGRAVURE Cylinder

MICROGRAVURE Coating Method
One of the main applications of ultra-thin polymer films being developed at MNTC is wound dressing, in which the films

Coating FluidDoctor Bladeare functionalized to close organ incisions after surgery forquick recovery. Associate Professor Okamura says that their

MICROGRAVURE Coating Method

most recent tests use ultra-thin polymer films of a few tens ofnanometers in thickness and a few centimeters square in area.

as Associate Professor Okamura explains, mulitple layers ofTourniquet tests have been made where these films are usedfilms are separated by spacers. The spacers are typically wa-to stop bleeding from rat livers.

ter-soluble. When the films become wet, the spacers slip out

From such tests, Associate Professor Okamura has foundthat it is essential to use multiple layers of ultra-thin polymer

and water enters the area left behind. In this way, the structure
looks like a mille-feuille pastry.

films in these types of applications. Although layering the films

Although monolayer films adhere well to the incision, theis necessary to increase the strength when attached to an or-pressure of the blood during bleeding may break the films. Asgan, the films themselves are not directly laminated. Instead,an alternative, thicker films can be used, but this results in poor
adhesiveness. Hence layering of individual layers was chosen,
which ensures both strength and adhesion. Associate Professor Okamura intentionally chose the liver for these tests because the high blood flow would help verify the performanceof the film. For example, they found that five layers of film weresufficient to stop bleeding from rat livers. Despite these results,a mass-production technology is still essential in moving to-Ultra-thin PolymerFilm Layers

wards practical application.
Junior Associate Professor Sunami, who works under Professor Hiromu Hashimoto, an internationally recognized leader
in web handling theory and professor at the Tokai University
Department of Mechanical Engineering, is in charge of mass-Ultra-thin Polymer Film Being Tested for Its Ability to
Stop Bleeding in a Rat Liver (provided by Professor
Yutaka Inagaki of the Tokai University School of Medical)

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production of ultra-thin polymer films using a wet coating rollto-roll process. Using MICROGRAVURE, a coating method
patented by Yasui Seiki Co., Ltd., Junior Associate Professor

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MICROGRAVURE, already used widely to produce ultrathin film coatings in industry, works like standard gravure. The
small-diameter gravure cylinder spins counter to the substrate
travel direction and picks up the coating fluid from a fluid supply pan, after which a doctor blade scrapes the excess coating
fluid from the cylinder. An extremely small, stable bead forms
between the spinning cylinder and substrate, providing the resulting film with excellent thickness uniformity.
According to Junior Associate Professor Sunami, the maximum coating width of the PLLA fluid at this point is 100 mm
and the coating speed is 5 m/min. A coating fluid PLLA concentration of 1% will form a wet film of 6 μm in thickness andMICROGRAVURE Coating Machine at MNTC

a dry film of about 60 nm in thickness. By adjusting parameters such as gravure cylinder rotational speed and coating

Sunami first applies a layer of water-soluble polyvinyl alcohol

fluid concentration, Junior Associate Professor Sunami has(PVA) onto a 100 μm thick PET film. Then, L-type polylactic

achieved a thickness precision in the width direction of ±10%.

acide (PLLA) is coated onto the PVA layer, dried in hot air, andThe influence of hot air convection currents on the film is con-rewound. Finally, the PVA layer is dissolved in water to produce

trolled using their know-how acquired through previous web

fairly large amounts of free-standing ultra-thin PLLA films.

handling research.

The Freedom to Research
MNTC originated from the Tokai University Micro/Nano StudyGroup, an interdisciplinary, self-initiated research association
made up of young researchers that got its start in the summer of2013. The impetus behind the group’s formation was a meeting
held around that time on campus at which Professor Kita andthe current members had an opportunity to meet each for thefirst time. Junior Associate Professor Sunami says that none of
the members had spoken before then, and at best they knew
each other’s names and had a vague idea about their research.
Despite their lack of prior history, the members immediately hit
it off and decided to meet again with the intension of working to-Class 1000 Clean Roomgether on some project. Junior Associate Professor Sunami was
not in attendance during the original meeting, but met up withOkamura’s ultra-thin polymer film given its originally, future out-

the group later at the invitation of Professor Tsuchiya.

look, and the potential for all members to utilize their strengths.

The group spent an entire weekend debating the topic of re-Professor Hashimoto and other veteran professors at Tokai Uni-search. As a result, they decided to focus on Associate Professor

versity responded to this initiative by the younger researcherswith support for the study group’s activities. From there, theiridea suddenly took-off and led to the establishment of MNTC.
Despite there only being eight members, Professor Kita says
the group is far from closed. Rather, he says they want MNTC
to evolve into a location for communication between different
groups, including students and professors of Tokai University,
outside researchers, and private companies. For this reason,
MNTC began its CORE TIME COFFEE, an open brainstorming
session held every Monday, Wednesday, and Friday afternoon at3 pm that anyone can attend. A comment by Professor Tsuchiyasums up the atmosphere of the MNTC. He says that every mem-Cell Culture Room Is Equipped With All theNecessary Equipment for Research54

ber of the group chooses to be here, and they are doing exactly
what they want.

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September / October 2016

In addition, Junior Associate Professor Sunami says thatcium. Tiny polymer particles are dispersed into this gel, which

his research also focuses on the anisotropy of the mechanicalis then physically pressed and the gel chemically removed tostrength of the ultra-thin films. This is a capability specificallyextract the disk-shaped ultra-thin polymer films. Particles withbased on their understanding of web handling theory and willa diameter of 1 μm, for example, will produce disks with a di-

be important in producing wider films when there is a demandameter of 1.6 μm and a thickness of 100-200 nm. Currently,

for higher productivity in the future.

they are working with polystyrene polymers, but PLLA is also
an option.

From Webs to Platelets

The surfaces of the disk-shaped ultra-thin polymer films

In addition to producing long sheets of ultra-thin polymer films

can be modified so that the nano-disks dissolve blood clots

in a roll-to-roll process, the team is also working on smallerwhen injected into the blood. In addition, Associate Professor

disk shaped ultra-thin polymer films. This was one of Associ-Okamura is focused on the development of a vascular disease

ate Professor Okamura’s research themes prior to arriving at

model to speed up this research.

Tokai University.
Associate Professor Okamura says that some 10 years ago

A Flood of Original Ideas

he was part of a team focused on functionalizing platelets in

Although this ultra-thin polymer film has the potential to change

the blood with nano-particles. Typically, platelets in the blood

the future of medicine, the team must first investigate the viabil-

will gather near damage in a blood vessel to close any open-

ity and safety of the films, as well as conduct countless tests

ings. Cancer patients receiving anti-cancer drug treatments,from different perspectives. This work is handled by the young,however, have drastically low platelet counts and there areenergetic researchers in the "Test" and "Know" groups. Mem-many people whose platelets do not function properly to begin

bers of the Test group include Professor Kazuyoshi Tsuchiya ofwith. As such, he felt it would be extremely beneficial if it were

the Department of Precision Engineering; Assistant Professor

possible to artificially create a replacement for platelets.

Asako Otomo of the Department of Molecular Life Sciences,

The research team Associate Professor Okamura was part

Basic Medical Science and Molecular Medicine, Tokai Uni-of at the time developed a nanoparticle in which the surface

versity School of Medicine; and Associate Professor Hiroshi

was modified with a special molecule that could recognize

Kimura of the Department of Mechanical Engineering.

damaged parts of blood vessels. They confirmed that theProfessor Tsuchiya is a pioneer in developing the world's

nanoparticles had the potential to stop bleeding when in-finest painless hypodermic needles. His focus is on combin-

jected into the blood, but they also recognized that flat, disk

ing the technology of painless needles and ultra-thin polymer

shaped particles would be more effective than the sphericalfilms to fabricate a novel sensing device designed to measureparticles they were using. They also saw the potential to use

blood pH and glucose levels. Assistant Professor Otomo is in

the nanoparticles as the carrier in drug delivery systems.

charge of developing medical applications for cell culture andDuring this stage, around 2010, their work required a fairly

cytopathology. She is an expert in the field of cell culture, in-complex process that combined UV photolithography andcluding differentiating nerve cells from ES and iPS cells, and isself-organizing monomolecular film technologies to produce

involved in growing biological cells for clinical testing. Associ-disk shaped objects with thicknesses on the nano-scale. Afterate professor Kimura is in charge of developing devices usingtransferring to Tokai University, however, Associate Professor

these films for specific medical applications. For example, heOkamura continued with his research and succeeded in de-has developed micro-fluid devices closely modeled on internalveloping an extremely simple generation process for the disks.

structures, such as the blood vessels that connect the liver,

The approach uses alginic acid, a compound found in sea-

small intestine, and cancer cells found in the lungs. These de-weed (brown algae) that instantly gels when mixed with cal-vices allow for research that simulates how metabolic products(substances absorbed by the small intestine and metabolized
in the liver) affect cancer cells. This technology is essential to

Physically
Pressedtesting the viability of disk-shaped ultra-thin polymer films.
The "Know" group consists of Assistant Professor So Nakagawa of the Department of Molecular Life Sciences, Basic
Medical Science and Molecular Medicine, Tokai University
School of Medicine; Associate Professor Kazuya Kabayama

Process for Forming Micro-particles Into Disk Shapes

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ka University (formerly of the Institute of Glycoscience, Tokaisurfaces of the needle. A homogenizer is used to fragmentUniversity); and Professor Kita. With the goal of establishing

the macroscopic films into microscopic pieces. The surface

a method to evaluate the interaction between thin films andof any object dipped into the solution of microscopic pieces

cells, Assistant Professor Nakagawa analyzes this interaction

will become covered with tiny pieces. As a result, the func-

at the genetic level using genome analysis technology. Asso-tionality of the ultra-thin polymer film surfaces is transferred tociate Professor Kabayama, one of the founding members of

the surface of the object. This approach also works to com-MNTC, is specialized in observing living cells (live cell imaging),

pletely cover microscopic surface unevenness. At present,and works on application to cell and drug screening. Professor

this technology is utilized to modify the inside surface of theKita analyzes the ultra-thin polymer film structure and function

painless microneedle developed by Professor Tsuchiya, whichusing molecular property analysis and rheology analysis.

has gained positive attention as a means of developing novel

To achieve the ultimate goal of applying ultra-thin polymer

sensing devices.

films to the human body, the team must still overcome many

Professor Kita goes on to say that they also assume thesehurdles on their path. As such, the research also considersfilms will be used in operating rooms. Although produced in aapplications more focused on the near future. Additionally,standard environment today, it will thus be necessary to pro-Professor Kita comments that the main strength of the MNTC

duce these films on roll-to-roll equipment in a contaminant-members is that they are all young researchers, which means

free, clean environment. The films will also be cut into the de-they constantly bring new ideas for various applications. All thesired shape and packaged in a clean room, only being opened

team members are also extremely dedicated to both researchagain in the operating room immediately before use. Givenand education.

these criteria, Professor Kita says it will be necessary to go

Instead of using large films, the new concept proposed

beyond the bounds of their research institute and cooperateby Professor Kita is to use fine, fragmented films to modify allwith private businesses. As such, he looks forward to working

kinds of surfaces such as microfluidic channels and the innerwith companies that are interested in their research.

Dr. Hashimoto of Tokai University Wins JSME Award for Technological Achievement
Established nearly 60 years ago, the Japan Society of MechanicalEngineers (JSME) has held its JSME Awards annually since 1958. Inaddition to the three JSME awards for “Academic Papers,” “Technology,” and “Technological Achievement,” JSME also offers honorable
mentions (research, technology) thatcelebrate young JSME members, aswell as the JSME Education Awardto highlight educational activities inmechanical engineering and otherindustrial fields.
In recognition of his contributions to systematizing and applying
web handling theory over the past

From Left, JSME Award for Technology,
Technological Achievement,and Academic Papers

30 years, JSME bestowed the 2015
Technological Achievement Award on Professor Hiromu Hashimoto of Tokai University. In
1990 Professor Hashimoto received the Academic Paper Award for his research in the fieldof tribology and in 2010 received the Technology Award for his work in web handling. Professor Hashimoto is one of the few, if only, people to have received all three awards.
Dr. Hashimoto Holds theJSME Award Certificatefor TechnologicalAchievement56

In this way, his monumental work and continued research activities with a constantfocus on actual manufacturing processes have placed him in a position that publishingcutting-edge academic papers and contributing to new commercial product development
alone could not have done alone.

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September / October 2016