Impact Objectives• Develop a fabrication process of sophisticated nanostructures with spatio-temporalcontrollability• Explore the use of actively tunable plasmonic structures

Pioneering researchin nanostructures

Learning from living things

Associate Professor Hideyuki Mitomo is creating innovative devices and he describes the important realworld applications they may have
Could you outline
the focus of yourresearch?
My research
focus is on thefabrication of highly
designed metalnanostructures, including 3D and 4D
structures, which are realised using spatiotemporal control. Living organisms havemade great systems using only limited andfamiliar elements, such as carbon, nitrogen,hydrogen, oxygen and phosphorus. They arelikely driven to do so as a survival strategy.
So, biomacromolecules, such as proteins,
DNAs and lipids, can have great functions
due to the sophisticated nanostructures
formed through self-organisation. They
are soft matter and we are interested intheir flexible structures and/or dynamic
conformation changes, including assemblyand disassembly, as a source of emergent
functions.

When I was a student, I learned aboutlife sciences, especially proteins andlipids. I was particularly interested in selfassembly, and molecular recognition orfunctions were my interest. So, I conducted
research on membrane proteins and lipid
membranes. I later moved to the ResearchInstitute for Electronic Science at Hokkaido
University, where I was introduced to metalnanostructures and began using metal
nanoparticles. Metal nanostructures are very
interesting functional materials.

Think of it as a ball being caught by a glove
in baseball. We are looking at the active
gap tuning of gold nanoparticle arrays andorientation control of the gold nanorod
arrays. Using this system, we can develop
tunable optical antennae or plasmonic
devices and, in the future, even more
impressive devices. In our system, insteadof molecules, we are using more attractive
components with plasmonic functionalities
and so we anticipate that it has great
potential.

What do you anticipate the impact of yourstudies will be?

Are there any results so far that you areparticularly pleased with?

I am interested in the use of plasmonic
structures. Plasmonics is a relatively new
research field. But there is already a huge
number of reports on the science andapplications, such as photonic antennaeand sensors, for example. Understanding inthis area is greatly expanding and creating
new possibilities. I believe our approach hassignificant potential at some parts.

We’ve developed a SERS (surface enhanced
Raman scattering) system, which is a very
useful sensing approach, with actively
tunable plasmonic structures. This is atypical and essential example of work I
am proud of. This will be a useful device
for biosensing, which is very important inmedicine and social security. I believe we
can make additional useful and functional
devices in the near future.

What is the goal of this work?
As it is possible to handle various elements,
it is expected that we can prepare highly
functional devices, which never exist in
living organisms and nature known as
meta-materials, once we have developed
a fabrication process of sophisticatednanostructures made of metals or otherelements.
How did your background lead you toresearch of this type?
54 www.impact.pub

You are interested in how active structurechanges of metal nanostructures canproduce different functions. Can you talkabout what this involves?
For active structure changes, there are many
examples in living organisms, one of whichis enzymes. They form open structures andwait for targets. When they catch a target,they start working as a catalyst. Oncethey’ve finished their work, they return tobeing open structures. This open form isconducive to efficiently catching targets.

What are your next research plans?
I plan to continue basic research, using
anisotropic structured nanoparticles,
prepare more sophisticated structuresand look into precisely controlling theirstructures. I am also eager to forge futurecollaborations that will expand our systems
and help us to develop invaluable devices
with very real applications. l

Scientists at the Molecular Device Laboratory, Hokkaido University are taking inspiration from living
things in their creation of self-assembled nanoparticles, which could ultimately be used in a range ofbioengineering applications

There is a lot to be learned from nature,in countless ways. Just one of these ways
is observing and replicating the complex
structures found in nature, particularlyon the nanoscale where all is small butmighty. Imagine if you could take inspirationfrom natural nanostructures to create
impressive nanorobots with a number of
exciting applications? At the Molecular
Device Laboratory at Hokkaido Universityin Japan, an intrepid team of researchers is
looking into fusing biomolecular science andnanotechnology to create powerful bio- or
nano-devices with manifold applications.
The research work is funded by a Grantin-Aid for Scientific Research (KAKENHI)
from JSPS and some other funding sources.
Associate Professor Hideyuki Mitomo heads
up the group, working alongside Professor
Kuniharu Ijiro, and some collaborators
including a collection of ambitious students.
Their work relates to the themes of materialscience, nanotechnology and life science. ForMitomo, an original interest in life sciences(molecular biology), especially proteins andlipids, transformed into an avid interest in
metal nanostructures and nanoparticles. And
now he is combining the two in pioneeringresearch.
THE PERFECT FUSION
This research surrounds an exciting area,
the emergent fusion of biological functions
and nanotechnology. This means that theresearchers are exploring the functionalfeatures of biomolecules and nanotechnology,
with a focus on metal nanoparticles. They areinterested in how the two can work together;
combining their respective attributes withimpressive results. To this end, Mitomo
and the team are looking at developing
nanodevices using soft matters such as
biomolecules, as well as creating biodevices
using metal nanoparticles. ‘The former
pertains to the application of biomolecules
to nanotechnology,’ highlights Mitomo. ‘Inessence, the researchers are working tocreate functional molecular devices by using
biomolecules such as proteins, nucleic acids,
lipids and sugars, or at least their features.’
The latter involves the use of nanomaterials
for biological applications. The team believes
this work could produce devices that will beuseful in a range of biological fields. A good
example of this is drug delivery carriers being
able to control properties such as the sizeand shape could be extremely useful here.
One particular area of interest for Mitomo
and the team is the creation of 4D metalnanostructures. These nanostructures arebuilt incorporating lessons from nature.
They mimic the sophisticated systems ofliving organisms. ‘Enzymes show dynamic
structural changes in their activity, which
is why they are sometimes referred to as‘Pac-Man’. Lipids form membranes and small
capsules via self-assembly and dynamic
structural changes as budding and fusion,
providing active substance transportation
functionality,’ explains Mitomo. ‘Actin
protein forms actin filaments and work as acytoskeleton via active assembly/disassemblytuning. So, we can learn from living things
that sophisticated nanostructures can provide
highly functional devices.’
An example of the enzymes that Mitomois referring to is CRSPR enzymes. They arelikened to Pac-Man as they have the ability,
once activated, to chew up RNA. There areother functions they can do too, and it isthese Mitomo is looking into. He provides
an insight into what the creation of 4D metalnanostructures involves. ‘It’s like a functional
nanomachine or nanorobot,’ he says. ‘Ifyou can imagine how an enzyme works like
Pac-Man, you can feasibly understand how
a metal or robotic Pac-Man can work evenbetter and be ascribed various functions.’
GOING FOR GOLDOne line of investigation for the team is‘Structure Control of Self-assembled Gold
Nanoparticle Arrays’. First, it is importantto note that metal nanoparticle arrays havebecome an exciting platform for manipulating
light-matter interactions at the nanoscale
which, in turn, creates a number of possible
applications. In terms of research work,
Mitomo’s focus is on the polymer-assisted
self-assembly of gold nanoparticles (AuNPs).
‘AuNPs show localised surface plasmon
resonance (LSPR), which means that acollective oscillation of electrons at the AuNP
surface is induced by the irradiation of lightwith a specific wavelength,’ he confirms. Thiscan vary depending on the size and shape ofthe AuNP, as well as the distance between
AuNPs. Polymers can be used to help tune
the assembly of AuNPs.
The research theme of ‘Structure Control ofSelf-assembled Gold Nanoparticle Arrays’
encompasses two research studies: ‘active
control of the self-assembled AuNP film on
the hydrogel’ and the other is ‘orientation
control of the gold nanorod (AuNR) arrayson polymer-grafted substrates’. In thewww.impact.pub 55

former, Mitomo and the team preparedself-assembled AuNP thin films on the solid
substrate and transferred them onto thepolymer hydrogel. They then tuned plasmonic
properties depending on the volume changeof the gel, as the gap distance of AuNPs inthe film was changed. ‘We found that byactively controlling the gap distance induced
increased signals of surface-enhanced Raman
scattering (SERS) through the improvementof the insertion efficiency of target molecules
for the detection into the gaps as hot spots,’
observes Mitomo. In the latter study, theresearchers established a new simple method
for the preparation of vertically aligned AuNR
arrays with controlled density. Now they areworking on active tuning of their orientation
by stimuli.
Building from this, the researchers arelooking at how they can selectively introduce
target matter into hotspots, which canincrease SERS intensity. ‘Our strategy isusing the lipid membrane. First, we entrap
them onto the lipid membrane and thenwe work on the two dimensional,’ Mitomo
confirms. The team is also looking into otherstructures that are composed of anisotropic
nanoparticles, but this is more challenging.
‘They are more attractive due to theirfunctionality but challenging,’ he reveals.

LEARNING FROM ENZYMESThe researchers are interested in the potentialof active plasmonic substrates, in particular.
In previous work they found that active tuningof the gold nanogaps (they are in their open
form for the insertion of target molecules
and in their closed form for the detection)
enabled them to function like enzymes.
They also explored the use of thermo and/or
photo-responsive nanoparticle vesicles, which
they believe has potential to be used as adrug delivery system.
The research team has made impressive
headway in its work to date, particularly giventhat it is a small team. This is one of thereasons why Mitomo values collaboration
so highly. ‘Resources are limited and we arechemists, which means we don’t have indepth knowledge on physics or other fields.
Therefore, partnerships and collaborations
are really important for us,’ he explains. ‘In
particular, in order to apply our systems toreal applications and to understand theirphotonic or plasmonic properties, a numberof researchers with different backgrounds
are required.’ Indeed, Mitomo welcomes new
research collaborations which could help
expedite his important work and faster bringabout real-world applications. l

Recent advances on nanoparticle assemblies for sophisticated nanostructures

56 www.impact.pub

Project Insights
FUNDING
These research projects were financially
supported by JSPS KAKENHI Grant
Number JP16K20870 and JP18H01804,and research grants from CASIO Science
Promotion Foundation, Tanaka Kikinzoku
Memorial Foundation, the Noguchi
Institute, The Sumitomo Foundation,
Suhara Memorial Foundation and JGC-S
Scholarship Foundation
CONTACT DETAILS
Associate Professor Hideyuki Mitomo
T: +81 11 706 9370
E: mitomo@poly.es.hokudai.ac.jp
W: https://chem.es.hokudai.ac.jp/en/BIO
Dr Hideyuki Mitomo received his PhD in2007 from the Tokyo Institute of Technology.
From 2007 to 2009 he worked at Lehigh
University in USA as a postdoctoral
researcher. After working as a postdoctoral
fellow at the Research Institute for ElectronicScience at Hokkaido University, he becamean Assistant Professor at Hokkaido
University in 2011 and he was promoted
to an Associate Professor in 2017. He iscurrently an Associate Professor at theResearch Institute for Electronic Science(RIES), and the Global Institution for
Collaborative Research and Education (GICoRE) at the Hokkaido University.