Booklet outlines
Creation and Achievements

02

Organization
LIMMS Recruiting Protocol
Scientific Policies
LIMMS Key Figures and Collaborations
Events

05
06
07
12
13

Host Laboratories
Members
Research Projects
EnergyQuantum and Molecular Tech.

16
22
23
24
32

Bio
Publications
Acknowledgements

41
64
69

1

Welcome to the Laboratory for
Integrated Micro-Mechatronic Systems(LIMMS/CNRS-IIS IRL 2820)

Creation andachievements

LIMMS was created in 1995 as a cooperation
unit between CNRS (SPI Department and now
CNRS Ingénierie) and IIS, the University ofTokyo. It was located in the Roppongi Campus(Tokyo/Minato-Ku).
Soon
after
it
was
established, the laboratory benefited largely
from the strong support from the Japan Society
for the Promotion of Science (JSPS).

LIMMS (Laboratory for Integrated Micro
Mechatronic Systems) is a joint laboratory
between CNRS (INSIS Institute for Engineeringand Systems Sciences) and the University ofTokyo (IIS - Institute of Industrial Science).
LIMMS researchers are hosted in 17 researchgroups mainly located on Komaba ResearchCampus of the University of Tokyo. Since its
creation in 1995 the laboratory has beenworking in the field of micro/nanotechnologies
and BioMEMS.

In 2000, LIMMS was relocated, together with IIS,
tothe
KomabaResearch
Campus(Tokyo/MeguroKu),
where
exceptional
technological facilities are provided.

SMMIL-E, Lille
LIMMS, Tokyo

2

1995

3

2023 - 2024

creation of LIMMS

research axis

428papersgrants24

EnergyQuantum & Molecular Tech.
Bio

2019-2024 JSPS C2C
2019-2025 CREST-JST
2022-2029 PEPR MoleculArchiv…

202023 - 2024

Since 2004

conferences

500
575
paperscontracts

90

peopleinvolved
in LIMMS
activities

Since 1995

conferences

46 CNRS researchers
23 CNRS post-doc
ecoLIMMS started
78 JSPS post-doc
14 IIS post doc
10 CNRS Research Eng.
people welcome
32 PhD students
88 Internships
New researchteams created in
22 administrative staff
France by former

2023

380

16

…

3

LIMMS members

v

Since the acquisition of a status of IRL 2820 in2004 (IRL= International Research Laboratory),

Investissement d’Avenir). In 2019, a second
JSPS Core-to-Core program (JSPS) was

LIMMS has been eligible to apply for French,
Japanese and European research projects andassigned to LIMMS (April 2019-March 2024) topromote the interactions more specifically in

grants-in-aid.

Bio-oriented activities with SMMiL-E and thepartners of iLite. In 2020, a CREST (JST) project

After successful review meetings, LIMMS wastargeting thermal management in silicon
devices was attributed to LIMMS (October 2019-

renewed for two terms (2010-2021). During thisperiod, LIMMS extended its structure to

March 2025). In 2021, an Integrate Research
Network ‘LIMMS Kiko' (period 2021-2031) of theEuropean partners through EUJO-LIMMS, aproject funded by the European Union (Dec.

University of Tokyo centered on LIMMS
activities was started to extend connections with2011 - May.2016) along with a first Core-to-Core
program (April 2012 - March 2017) of the JSPS.

55 Japanese professors from 8 Institutes andSchools including fields such as engineering,

In 2014, LIMMS took a new step in its
development by inaugurating a mirror location

medicine, information science and philosophy.
Finally, in 2022, LIMMS was involved in thein Lille (France) inside a hospital. The SMMiL-E
project, Seeding Microsystems in Medicine in

MoleculArxiv PEPR (French topical program) as
one of its key laboratories.

Lille, first research location of IIS out of Japan,
gathers IIS, CNRS, Centre Oscar Lambret andLille University.

In 2023/2024 about 90 people were involved in
LIMMS activities including Host Professors (17)and their teams, CNRS researchers (11),In 2017, LIMMS was involved as a partner of theiLite consortium (for innovation in Liver tissue

engineers (2), JSPS post-doctoral fellows (1),contract based post-doctoral fellows (7), PhD

engineering, 2017-2022), an university researchhospital project, granted by the French

students (5), internships (14), collaborators (27)and administration staff (6).

program-investment for the future (Program4

Organization

The University of Tokyo covers salaries of thegroup of host professors and provides alltechnological platforms (1200 m² of cleanrooms,
biological and biophysics experimental labs,
AFM characterization lab, etc.), as well as its
operational costs.

LIMMS combines the expertise of French andJapanese scientists in order to explore newscientific domains related to micro andnanotechnologies.
Researchers whoarerecruited by LIMMS are hosted in the Japanese
research groups affiliated to LIMMS. The
scientific interaction is thus optimal.

CNRS provides CNRS researchers salaries andthe annual research budget, in the frameworkof a collaboration contract between CNRS andIIS, The University of Tokyo.

LIMMS’ structure is organized to handle
challenging joint projects. These projects follow
the scientific policy promoted by both Directors(CNRS and IIS), and approved by CNRS
Ingénierie within its interdisciplinary policy withother CNRS Institutes, IIS and JSPS. Eachscientific project gathers a LIMMS researcher,the Host Professor heading his/her host lab(The University of Tokyo), and associated lab
members (see structure of LIMMS on the figure
above).

Research costs: salaries of researchers aresupported by both CNRS and IIS (CNRS, IIS
staff, post-doctorates, PhDs and trainees) or by
JSPS, JST, ANR or EU (post-doctorates andPhDs).

5

CNRS Permanent

LIMMS
Recruiting Protocol

French Univ.
professor

Post-doc

JSPS Post-doc

Ph.D student

1. How to apply to LIMMS/CNRS-IIS (UMI 2820)

IIS Host
Profs.

LIMMS
CNRS-IIS

IIS
Secretaries
CNRS ITAInternshipa. You have a CNRS researcher position
Step 1:(1) Visit to LIMMS for
several days
(2) Definition ofresearch subject

Step 2:
Validation
by LIMMS
And by yourlaboratory

Step 3:
Applying for LIMMS positionat INSIS (or institute you
belong to)

Step 4:
Approval by National
Committee
Decision from INSIS

Year N-1

Sep/Oct Year N-1

Autumn Year N-1

Autumn session Year N-1
or Spring session Year N

Arrival inJapan
Sep/Oct Year N

b. You are (associate) professor in French University
Step 1:(1) Visit to LIMMS for
several days
(2) Definition ofresearch subject

Step 2:
Validation
by LIMMS
And by your
University

Step 3:
Applying for“Accueil en délégation”
to move to CNRS
temporary position

Step 4:
Transfer of the application
with agreements to
the Regional delegationof CNRSYear N-1

Sep/Oct Year N-1

Autumn Year N-1

January Year N

Arrival inJapan
Sep N or Feb. N+1

c. You are Ph. D student (to apply for the JSPS Post-doc program )Step 1:
Positions appear in LIMMS
web sites and ABG

Step 2
Application screening by
LIMMS

Step 3:
Application screening
by CNRS and JSPS

Expected arrival
Sep. 1st – Nov. 30
for Spring Campaign

Spring Campaign

2 Campaigns / year

Step 1:
Positions appear in LIMMS
web sites and ABG

Step 2:
Application screening by
LIMMS

Step 3:
Application screening
by CNRS and JSPS

Autumn Campaign

Arrival inJapan

Expected arrival April 1 – Sep. 30
for Autumn Campaign

d. You are student (to apply for Master internship , French doctoral program )Step 1:
Position available at LIMMS andAdvertisement in web sites(CNRS, LIMMS )Step 3:
Transfer of the application
with approval to CNRS.
Recruiting protocols

Step 2:
Application screening by
LIMMS

Arrival inJapan

2. Service at LIMMS in Japan
HigherYour Potential
Research Accomplishment

Minimize leading
time before arriving at
LIMMS by giving
administrative
support :- Visa procedures- Housing information

Before arrival

Minimize leading time
before staring research bygiving administrative support:- House-hunting- Bank account opening- Kinder garden arranging- Health-insurance contract

EarlierYour arrival

Daily care to reach higher
potential.
Tasks to be transferred in part to hostlabs.
- English translation daily journals(from kinder garden)- Internet bug fix- Etc

FasterQuick curve to reach maximum potential by giving
additional administrative support:- External funding contract- Eligibility application for Grant-in-Aid- IIS Internal accounting service (CR charge etc.)- LIMMS related seminar organize- LIMMS Scientific Committee arrangement- LIMMS documentation (publication list etc.)- Lab budget accounting negotiation
between CNRS and IIS- Lab budget book-keeping (CNRS and IIS, UTokyo)

Your Staying Time with LIMMS

6

Scientific Policies

find solutions to power the Internet of Thing(IoT) based on energy harvesters integrated

Since 2023, the LIMMS direction has
highlighted three general fields of applications

The Quantum and Molecular Technologies
axis is a highly interdisciplinary field thatin micro and nanotechnologies by proposing
three specific research axis:

combines cutting research from physics,
chemistry, and biology. This axis bridges the• Energy

two other axes (energy and biology), while also
exploring its own unique research questions. At
the heart of this axis lies the exploration andintegration of quantum technology and• Quantum and Molecular Technologies• Biomolecular technology. Quantum technology isconcerned with the use of quantum mechanics

Those three fields are illustrating recent MEMS,
BioMEMS and Nanotechnology developments.

to develop new technologies as for instancemanipulating the transport of heat, electron or

They reflect the orientations of LIMMS in newtechnologies related to societal demands.

light, while molecular technology deals with thestudy and manipulation of molecules and theirproperties.
Our researchranges fromfundamental endeavor such single-electron

In Energy axis, LIMMS researchers obtained
worldclass results with the development oftransfer in electrochemistry to the storing ofphononic crystals for heat focusing. LIMMS
technologies are at the cutting-edge regarding

massive data in DNA, the sensing of
biomolecules, or the integration of electronic

thermoelectric
micro-devices
andhave
confirmed new concepts in thermionic cooling.

into our everyday life with flexible electronics.

Interface research programs are also settled to

7

The new Bio axis gathers three themes. Disease
treatment via prevention and detection isinvestigated by developing new devices fordiagnosis and vaccine delivery. With acomplementary approach, implantable tissues
and devices are also key activities.

especially cell interactions in diseased andhealthy tissues.
BioMEMS such as platforms with multi-modal
sensors and actuators are developed in LIMMS
to help investigating organ behaviour andcreate biohybrid systems. Biocompatible
materials and/or cells are also used to create
Bio-robotic systems. A particularity of the Bio
axis is the complementary contribution of aninternational team, SMMIL-E. Its activities arefocused on research against cancer, at theinterface between BioMEMS and Organ
modelling.

This branch is related to complex tissues
opening to organ modelling where the cellularand even the molecular scale are investigated.
Researchers seek to better understand theblood
vesselformation,theneuronal
communication behaviour and the interaction of
the metabolic organs such as liver andpancreas. By studying different organs, LIMMS
aims at understanding the role of tissues and

SMMiL-E (Seeding Microsystems in Medicine in Lille)
The SMMiL-E project includes the setting-up of a new platform of the Institute of Industrial
Science of the University of Tokyo (IIS) in the Lille university-hospital area, close to medical
teams. First research location of IIS out of Japan, this implantation is backed by CNRS, Centre
Oscar Lambret and Lille 1 University, as a IRL, International Joint Unit, mirror site of
LIMMS/CNRS-IIS (IRL 2820). The new site was approved by the four partners and inaugurated onJune 16th, 2014.
Goal : SMMiL-E aims at setting-up and implement a comprehensive research program on
BioMEMS against Cancer in a sustainable international high-level collaboration. The projectsynergizes Bio-MEMS research from LIMMS/CNRS-IIS with research against Cancer performed in
Lille under the labeled SIRIC ONCO - Lille program.
Research Activity in SMMiL-E
The scientific activities encompass BioMEMS research against Cancer, technology development
and bio related experiments, as an original interdisciplinary approach to the SIRIC ONCO-Lille
program. The projects aim at bridging fundamental and clinical research around four work
packages:
WP1 Biomolecular mechanisms of the tumor resistance to treatment (DNA degradation undertherapeutic irradiations, Microtubules stabilization in chemotherapy).
WP2 Cellular evaluation and diagnosis: Stem cells and circulating tumor cells detection andsorting, study of cell senescence and tumor dormancy.
WP3 Cells interaction and therapeutic targets: in vitro tumor angiogenesis, cellular mobility andmetastatic processes.
WP4 Biological adhesives and neotissues: cellular fibers and postsurgery recovery.

By means of an upstream research, this program targets more effective disease detection, astrengthened efficacy of therapy and posttreatment monitoring, for a better care to patient.

8

A CREST project (JST program) was awarded to LIMMS in October 2019 supporting theEnergy Harvesting and Management activities. This five years project (250 Millions Yen)
involves a single team, and aims at developing scientific understanding and demonstratorsof phonon polariton heat transfer in silicon micro and nanodevices.
This project involves three LIMMS researchers (from August 2020).

2019 - 2025

CREST (JST) project

PEPR MoleculArxiv
The dazzling amount of data that humanity generates requires novel solutions for long-term
storage. Storing data in the form of DNA, similar to living beings, is a promising option due
to its enormous density: 100 g of DNA could in principle store all the data kept indatacenters around the world.

2022 - 2029

The PEPR MoleculArXiv aims to make of France a key player in DNA storage by involving
more than 20 interdisciplinary laboratories from CNRS. LIMMS plays a key role as it is incharge of coordinating and integrating experimental and theoretical progress into ademonstrator that writes information in DNA at a rate of 1 bit per second -100x faster thancommercial synthesis in 5 years.
The PEPR will also foster French and European communities and aim to propose aEuropean FET-flagship. Applications will include cold data archiving, marking, calculation,and molecular engineering.
https://pepr-molecularxiv.fr/le-pepr/

LIMMS KIKO
The University of Tokyo Integrated Research Network

LIMMS KIKO, (LIMMS= “Laboratories for International Research on Multidisciplinary Micro
Systems”) was established April 1st 2021 for a period of 10 years and is based on the
LIMMS/CNRS-IIS IRL 2820, which has been managed by CNRS and IIS for 25 years as aJapan-France collaborative research center, in order to transcend departmental boundaries
and comprehensively bring in the intellectual creativities of the University of Tokyo.
https://kiko.limms-tokyo.org/en/

92021 - 2031

The LIMMS KIKO is engaged in a cross disciplinary research for the improvement of the
Quality of Life including mental, physical and cultural aspects and addressing societal
problems of aging and declining population which developed countries will face, byapplying the results of international collaborative research in the Micro-nanointerdisciplinary fields such as Nanobiology, μTAS, Silicon Neurons, IoT, and Energy
Harvester, etc.

JSPS Core-to-Core program JETMeE
Since 2012, the Japan Society for the Promotion of Science (JSPS) has
implemented the Core-to-Core Program, comprising two components: (A)Advanced Research Networks and (B) Asia-Africa Science Platforms.

This program aims at creating world-class research hubs and foster young
researchers through networking to advance multilateral collaboration in cuttingedge fields of science. It funds matching activities to SMMiL-E and iLite bysupporting UTokyoIIS to send Japanese researchers to CNRS and EPFL and to
reinforce scientific collaborations. The Program name is JETMeE in frame of theCore-to-Core, meaning “Japan- Europe Research Hub for Translational Medical
Engineering”.

2019 - 2024

In 2019, a second JSPS Core-to-Core program was assigned to LIMMS (April
2019- March 2024)to promote the interactions more specifically in Bio- oriented
activities with SMMIL-E and the partners of iLite. JSPS granted “Core-to-Core (A)advanced research networks program” to the Institute of Industrial Science (PI:Prof. Beomjoon Kim, LIMMS director) with a 15 Million Japanese Yens / Year, for
5 years, as matching fund to SMMiL-E, iLite, and EPFL research funds.

https://www.jetmee.jp/“We are part of the problem, so let’s be part of the solution.”
EcoLIMMS is a group of researchers who share a commitment for climatechange questions, and ask ourselves how we can, as researchers, have a positive
impact on the planet. EcoLIMMS was formed in April 2023.

The two main missions established are: (i) act at the laboratory scale, and (ii)organize events to communicate on scientific research and climate change(beyond the lab).

Regarding the events, a crosstalk event was organized in February 2024 with aresearcher from Human and Social Sciences and another one from Science andTechnology. Other events will be organised over the coming year. This action isin line with the commitments of the CNRS and The University of Tokyo.

102023 ~At the lab scale, a monthly newsletter is sent to the lab members to share
information on a selected topic, and on specific events related to climate change
and environment. The work group has also started working on the greenhousegas balance of LIMMS which is an interesting tool to evaluate and then optimize
our behaviours and practices.

International Research Network EURA-LIMMS

IRN

The EURA-LIMMS network aims to create a Europe-Asia network for thedevelopment of innovative technologies in energy, bioengineering, andmolecular sciences. The objective is to revive the success of the NAMIS
network supported by the CNRS, by adapting the themes to the current
research axes of LIMMS. The network will promote the education of
students and the exchanges between member teams from: The Universityof Tokyo, Seoul National University, National Taiwan University, National
University of Singapour, EPFL, Helmoltz, Imtek, University of Twente and
CNRS.
Contact : N. Clément

International Project Team – Equipe Projet Internationale

11

EPI

International Project Teams that are joining researchers of LIMMS and of a
CNRS laboratory in France on a given topic. The four following teams arepresently running: BioMeg with IMS in Bordeaux on Biomorphic science,
MinanoBio with LAAS in Toulouse on MIcro-&NANO-technology for BIOengineering and bio-sensing, TEAMS with BMBI on Therapeutics andEngineering Against Metabolic Syndrome and SUNRYSE with IM2NP in
Marseilles on Structured Nano-systems for energy conversion andmanagement. The teams no only activiate student and researcher
exchanges but also raise fund from CNRS and universities to promoteresearch works.

LIMMS Key Figures
and Collaborations

In this period, LIMMS members have managed
8 grants (5 by JSPS, 1 by JST and 2 by others)
and 20 contracts (EU, PEPR, ANR, Region...).

Since its creation, the LIMMS has welcomed in
total 380 members including 46 CNRS
researchers, 78 JSPS post-doctorates, 23 CNRS
Postdoctorates, 14 IIS Post-doctorates, 32 PhD
students, 10 CNRS research engineers, 34
collaborators, 2 industrial collaborators, 88internships, 22 administration staff, etc...
Since 2004, LIMMS has published more than
500 journal papers (including publications inhigh impact journals such as Nature /Chemistry, /Biotechnology, /Communications-,
NanoLetters, Physical Review Letters...), andmore than 575 communications to international
conferences.
In 2023-2024, our members published 42 journal
papers and 24 communications in international
conferences.

FormerLIMMS
members
maintaincollaborations with Japanese host professors
and CNRS laboratories in France (SAKURA
programs, PICS and JSPS Bridge).
More than 16 new research teams, often
followed by technology exchanges and sharing
from LIMMS, were created by former members
back in France.
LIMMS has also been pivotal to launchinginternational research networks such as the
CIRMM/IIS « Center for International Researchon Micro nano Mechatronics », the « Global
Research Network » of IIS and the NAMIS «Nano Micro Systems » linking CNRS to IIS andto prestigious institutions such as EPFL, SNU,
VTT, IMTEK.

More than 380 researchers in total hosted since 1995
Number of internship and short term researchers decreased
in FY 2021-2022 due to the Covid-19 crisis

12Events
LIMMS International Workshop on Micro-and NanoTechnologies for Energy, Bioengineering and Bio-sensing with JETMeE Workshop, Oct. 25-26, 2023.
On October 25th and 26th 2023, an International Workshop on Micro-and Nano-Technologies for Energy,
Bioengineering and Bio-sensing with JETMeE Workshop was held in IEMN CNRS, Lille (France). A group ofJapanese host Professors from LIMMS and IEMN researchers presented their activities to open forcollaboration. LIMMS alumni and potential candidates were also present. (Co-organizers: LIMMS and IEMN
Directions).

Workshop on CNRS - Industry Collaborations (IWCIC), Jun. 13-14, 2023.

On June 13th-14th, to mark the 15th anniversary of CNRS's collaboration with NTT on nanoand molecular components, LIMMS organized a workshop [International Workshop on
CNRS - Industry Collaborations (IWCIC)] featuring 9 industry presentations and a "rumpsession" for students and young researchers to ask questions. (Co-organizers: Nicolas
Clément, Imran Mahboob, Akira Fujiwara).

13

JFK Workshop on Emerging Biomedical Science and Technology at the Nanoscale, Oct. 10-11, 2023

The JFK2023 (for Japan-France-Korea) workshop on emerging biomedical science and technology
at the nanoscale was co-organized by LIMMS October 10th and 11th 2023, in two campuses of the
University of Tokyo. Participants came from various institutions such as Paris-Saclay University, France,
Pusan National University, Seoul National University, South Korea and The University of Tokyo, Japan.
The second day of workshop was jointly held with the NANOHUB of The University of Tokyo. (Coorganizers: Gilgueng Hwang, Yoshio Mita, Pierre-Yves Joubert, Giancarlo Faini).

LIMMS Steering Committee 2024, Oct. 24, 2023.

On October 24th 2023, the LIMMS Steering Committee was held in CNRS headquarters, Paris. The
IIS Director, Professor Toru Okabe and the LIMMS Direction with Professors Yoshio Mita and Soo
Hyeon Kim met the direction of the CNRS Ingénierie institute, including Maria-Pilar Bernal,
Deputy Director, Béatrice Dagens, Deputy Director for International Affairs, Olga Allard,admnistrator for International Affairs.
3rd Aix-Marseille University/IIS UTokyo, Oct. 31, 2023.

On October 31st, the 3rd Aix-Marseille University/IIS UTokyo Workshop on optical and electronic
devices was co-organized with LIMMS in IIS. Speakers from the IM2NP laboratory and the Institut
Fresnel of Aix-Marseilles University on one hand and from IIS in the other hand took part in theWorkshop. (Co-organizers: Kazuhiko Hirakawa, Marc Bescond).

14

UTC joint workshop, Oct. 31~ Nov. 6, 2023.

In the frame of the collaboration between The Université de Technologie de Compiègne (UTC),
IIS, and CNRS, Professors Sakai and Minami co-organized a joint workshop and a UTC visit
delegation held in Tokyo from October 31st to November 6th. The workshop was an opportunity tointroduce French and Japanese advanced research programs, recent innovations. 68 participants
registered. The UTC delegation, headed by the president of the UTC, Prof Rossi, took theopportunity to renew the IIS MOU, exchanged with Prof Okabe, IIS general director, anddiscussed future collaboration with Prof Fujii, the president of the University of Tokyo.

SMMiL-E/UTC 2024 School on BioMEMS, (4th Ed.) Feb. 6~16, 2024.

SMMiL-E, the site of LIMMS/CNRS-IIS IRL 2820 in Lille, hosted an international school on
bioMEMS in collaboration with BMBI CNRS laboratory of UTC (University of Technology ofCompiègne), from February 6th to 16th, 2024. This educational event, held for the fourth time,
aimed to introduce the main aspects of bioMEMS technology through a multidisciplinary team
(22 lecturers in Lille and 8 lecturers in Compiègne) with backgrounds in biology, clinics andengineering. The school's contents were grouped into three main categories: device
development (e.g., design, fabrication, characterization and operation), fundamental techniques(e.g., biological, clinical and microfluidics) and examples of applied systems (e.g., organ-on-a-chipand single-cell analysis).
7 students from the Institute of Industrial Science, The University of Tokyo, 19 students from the
University of Lille, 2 students from JUNIA and Polytech Lille (French graduate schools of scienceand engineering), and 10 students from UTC attended this program and were highly encouraged
to join projects between SMMiL-E, UTC and IIS.

15

Host Laboratories

Pr. Kazuhiko HIRAKAWA• MEMS/NEMS-basedterahertz detectors• Semiconductor
heterostructure thermioniccooling devices• Single molecule/quantum
dot transistors• Terahertz dynamics ofquantum nanostructures forquantum information
processing

http://thz.iis.u-tokyo.ac.jp

Associate Pr. Yoshiho IKEUCHI• Neural tissue engineeringand brain organoids• Neuronal morphology anddevelopment• Protein synthesis inneurons• Human pluropotent stem
cell-derived neurons

www.bmce.iis.u-tokyo.ac.jp

16

Host Laboratories
Pr. Hideki KAWAKATSU• Color AFM with chemical
contrast• Force and vibration
measurement ofreproductive cells• Quantitative color AFM
through Molecularfunctionalisation of AFM
tips

www.inventio.iis.u-tokyo.ac.jp

Pr. Beomjoon KIM• MEMS, Bio-NEMS,
Micro/nano patterning, soft
lithography• SAM patterning for cell
culturing/bio sensors• Heat transfer in nanostructures, Micro/nanoheaters for molecularEngineering

Healthmonitoring
Microneedles
patch• Microneedle patch for new
drug delivery system• Energy harvesting, power
MEMS

www.kimlab.iis.u-tokyo.ac.jp

Lecturer Soo Hyeon KIM• Microfluidics-on-CMOS• Single cell analysis• Single molecule detection• Cell-cell interactions• Biomedical microsystems
for liquid biopsy• Parallelized flow cytometrywww.shkimlab.iis.u-tokyo.ac.jp

17

Host Laboratories
Pr. Takashi KOHNO• Neuromimetic siliconneuronal network
circuits and theirapplication toneuromimetic artificial
intelligence• Architectural design ofthe neuromimetic
computingwww.neumis.iis.u-tokyo.ac.jp

Associate Pr.
Naoji MATSUHISA• Stretchable electronicmaterials and devices• Wearable devices• Human-computerinterfaces• Electronic skins for
robotshttps://www.naojimatsuhisa.com/

Pr. Yukiko MATSUNAGA• Tissue engineering• Biomaterials• In-vitro microvessels
model• Vascular biology
www.matlab.iis.u-tokyo.ac.jp

18

Host Laboratories
Associate Pr. Tsuyoshi MINAMI• Organic TFT-based
chemical sensors• Supramolecularsensor arrays

www.tminami.iis.u-tokyo.ac.jp
Pr. Yoshio MITA
• Integrated MEMS-VLSI
technology• Nature Engineered
Microdevices• Nano deep 3D MEMS
optoelectronic systems• Autonomous microrobot• Bio-inspired perception
LSI systems

http://www.if.t.u-tokyo.ac.jp/

Pr. Masahiro NOMURA• Physics of nanoscalephonon/heat transport• Nano-Si thermoelectricenergy harvesting• Quantum transducer via
spin-optomechanics
https://www.nlab.iis.u-tokyo.ac.jp/

19

Host Laboratories
Pr. Yasuyuki SAKAI• Physiological micro cell
culture system (MPS) basedon microfluidics,
micropatterning andhierarchical cellularorganization• 3D microfabrication andbiofabrication for engineeringof implantable tissues• High-cell density propagationand differentiation ofstem/progenitor cells

http://orgbiosys.t.u-tokyo.ac.jp/sakai/

Pr. Takao SOMEYA• Flexible electronics usingorganic transistors• Large-area sensors andactuators• Molecular/organic
electronics• Printing technologies forlarge-area electronics• Printed MEMS switches for
power transmission

www.ntech.t.u-tokyo.ac.jp

Pr. Takuji TAKAHASHI• Multiple analyses of solar
cell materials by photoassisted nanoprobes• Development of novel
measuring methods toimprove performance in
SPMs• Analysis of individual finecurrent paths in CNT-FETs
by MFMwww.spm.iis.u-tokyo.ac.jp20

Host Laboratories
Pr. Shoji TAKEUCHI• Biohybrid MEMS
• Membrane protein chips• MEMS for articial cells• Neural interfaces• Microchambers,
droplets, capsules
www.hybrid.t.u-tokyo.ac.jp
Associate Pr. Agnès TIXIER-MITA• Thin-Film-Transistor platform
for multi-modal bio-sensing• Real-time biomimetic
platform for neuro-cardiac
investigations• Systems for simultaneous
optical and electricalmeasurements on
cardiomyocyte cell culture

http://toshi.iis.utokyo.ac.jp/toshilab/?Members/Agnes+Tixier-Mita

Pr. Hiroshi TOSHIYOSHI• Optical MEMS
• RF-MEMS• THz metamaterials• CMOS-MEMS
integration• Energy harvesters

http://toshi.iis.u-tokyo.ac.jp/toshilab/

21

Members
Director (IIS)

Director (CNRS)

Masahiro
NOMURA

Sebastian
VOLZ

Administration
Yumi HIRANO – Administrator
Sachie HIRANO - Assistant
Eiko KANEKO - AssistantKanae TOBE - Assistant
Aki KIUCHI - Assistant
Yuka François TAKASE- Assistant(CNRS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(CNRS, Lille)(CNRS, Lille)

Researchers
Nicolas CLÉMENT
Anthony GENOT
Gilgueng HWANG
Eric LECLERC
Jose ORDONEZ MIRANDA
Vincent SALLES
Dominique COLLARD
Fabrice SONCINÇağatay TARHAN(CNRS, Tokyo)(CNRS, Tokyo)(CNRS,Tokyo)(CNRS,Tokyo)(CNRS,Tokyo)(CNRS, Tokyo)(CNRS, Lille)(INSERM Lille)(JUNIA, Lille)

Research Engineer
Robin DETEIX
Laurent JALABERT(CNRS,Tokyo)(CNRS,Tokyo)

Post-doctoral Researchers
Gwenaël BONFANTE
Simon GRALL
Shuo LI
Dorina PAPANASTASIOU
Sona ROY
Jean-Claude GERBEDOEN
Faruk Azam SHAIK
Dana SIMIUC(JSPS, Tokyo)(CNRS, Tokyo)(JSPS, Tokyo)(JSPS, Tokyo)(CNRS, Tokyo)(CNRS, Lille)(CNRS, Lille)(SATT, Lille)

Ph.D. Student
Hajar AJIYELHenri VO VAN QUIBahram AHMADIAN
Ibtihal HEZILI
Alice LEROY(IIS, Tokyo)(IIS, Tokyo)(JUNIA, Lille)(Univ.de Lille)(Univ.de Lille)Internship Students
Félix BARBIER
Céline BELABBAS
Elias BOUDJELLAGaël BUI VAN
Aramis DUFOUR
Adrien GADYLouis GRANDVAUX(IIS/LIMMS, Tokyo)(CNRS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)

22

Axel LEVY
Julie RAUDE(OGUCHI)
Helen SANDS
Arthur SUREAU
Amira BOUSBAA
Celia LEZIER
Léonore LHUILLIER(CNRS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(IIS/LIMMS, Tokyo)(CNRS/LIMMS, Lille)(CNRS/LIMMS, Lille)(CNRS/LIMMS, Lille)

Collaborators
Daniel ALCAIDE MARTIN
Baptiste ALRICPaul BRUAND
Jeremy CHESLET
Audrey COCHARDMaëlie CORAL
Michele DIEGO
Tomoya Luca DUENKI
Alex DUFOUR
Anne-Claire EILER
Theo FOSCHIA
Wang HANYUAN
Thomas MENIER
Carla MESCHINIIan SCHUMACHER
Sophie DABO
Dimitra GKIKA
Chann LAGADEC
Xuefen LE BOURHIS
Loïc LEMONNIER
Suman MITRADavid PASQUIERMaria Carla PARRINI
Yoann SOTTEJEAU
Yasmine TOUIL
Adrien VIALLETELLE(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(IIS, Tokyo)(Univ.de Lille)(Univ.de Lille)(INSERM, Lille)(Univ.de Lille)(INSERM, Lille)(Canther, Lille)(COL, Lille)(Institut Curie, Paris)(SATT, Lille)(Univ.de Lille)(ASYGN, Lille)

EPI Collaborators
Marc BESCOND
Guilhem LARRIEU
Cécile LEGALLAIS
Timothée LEVI(AMU-CNRS)(LAAS-CNRS)(BMBI,UTC-CNRS)(IMS-CNRS)IRN Director
Nicolas CLÉMENT(LAAS-CNRS)SMMIL-E, Lille

LIMMS, Tokyo

Research Projects
The laboratory operates in three fields:• Energy• Quantum and Molecular Technologies• Biology

Details about all research projects conducted from April 1st 2023 to the March 31st 2024 will be givenin the following part of the booklet.

23

Hosted in

EnergyAxis

24

CREST Project: Surface PhononPolariton Heat Transfer (2019-2025).
Sebastian Volz

Fundings:
JST-CREST
Kakenhi B

Hosted in Nomura Lab
Keywords: Radiation, Cooling, Nanoscale

Methods

Context and Objectives

Fabrication:
Clean-Room silicon processes.

Designing nanoscale heat spreaders insilicon devices.

Characterization:

Investigating a new heat transfer channel
based on SPhP in the in-plane direction.

Time-Domain Thermo Reflectance;

In ultrathin films at high-T, SPhPs are thepredominant heat carriers.
We aim at experimentally demonstrating
this prediction and then manipulate SPhP
by guiding, tunneling, rectifying andfocusing.

3 omega; IR Camera and FTIR.
Modeling:
Analytical solution of Maxwell;Boltzmann
Equations;

and

Heat

conduction

Fluctuational Electrodynamics (SCUFFEM open source code)

Tasks
Demonstrators include:•

Proof of concept••

Focusing and tunneling•

Trapping

Switching and rectifying

Perspectives

References

Design SPhP Diodes;
Exploiting 2D materials Polaritons;
Use SPhPs to control far-field thermalradiation.

[1] J. Ordonez-Miranda, et al., Physical Review
B 108 (16), L161404, (2023).
[2] J. Ordonez-Miranda, Physical Review
Applied 19 (4), 044046, (2023).

volz @ iis.u-tokyo.ac.jp
https://www.nlab.iis.u-tokyo.ac.jp25Modeling of the Heat Transport Driven by
Surface Electromagnetic Waves.
José Ordonez-Miranda
Hosted in Nomura Lab
Keywords: Surface phonon-polaritons,
Heat transport modeling, 2D heat radiation.

Fundings:
JST-CREST (S.Volz)
Kakenhi B

Context and Objectives

MethodWith the continuous miniaturization ofdevices with enhanced operation rates, theoverheating of the used nanomaterials has
become very challenging, as it limits theirapplications and wastes energy that ismainly released into the environment. We
are addressing this scientific challenge bystudying the heat transport not only inside
the nanomaterials’ volume but also along
their interfaces, via surface electromagnetic
waves. These waves are powerful heat
carriers that can enhance the heat transport
by phonons, photons, and electrons [1,2].
Our research aims to develop analyticaland numerical models for discovering new
physical effects and predicting thepolariton thermal energy.

Maxwell's equations of electromagnetism
for predicting the existence andpropagation of surface polaritons.
Boltzmann transport equation for finding
the temperature and heat flux profiles ofnanostructures.
Generalization of Fourier's law of heat
conduction and Stefan-Boltzmann’s law ofthermal radiation in 1D, 2D, and 3D
structures.
Development of theoretical models fordescribing
experimental
data
andmeasurement thermal properties.

Results
We have experimentally demonstrated a
two-fold enhancement of the far-fieldthermal radiation between two nonabsorbent Si microplates coated withenergy-absorbent SiO2 nanolayers (Fig. 1),
which support the propagation of surface
phonon-polaritons [1].
Fig.1 Measured thermal conductance between
two Si plates with and without SiO2 coating.

Perspectives
To compare the predictions of the
Boltzmann transport equation (particle
picture) with those of fluctuational
electrodynamics (wave picture) for thepolariton thermal conductivity of nanofilms,
nanowires, and nanostructured materials.

References[1] S. Tachikawa, J. Ordonez-Miranda et.al.,
Phys. Rev. Lett. 132, xyzabc (2024)[2] J. Ordonez-Miranda, Y. A. Kosevich et al.,Phys. Rev. B 108, L161404 (2023)

jose.ordonez @ cnrs.fr

https://www.nlab.iis.u-tokyo.ac.jp26

Enhancement of Emissivity via
Thermally Exited Guided Modes.
Maëlie Coral

Funding:
JSPS Kaken-hi B

Hosted in Nomura Lab
Keywords: Guided modes, Surfaces
phonon-polaritons, thermal radiation

𝑞𝑟𝑎𝑦

Context and Objectives

SiO2

𝑞%&'&(
SiO2

Surfaces
phonon-polaritons(SPhPs)areelectromagnetic surface waves generated by the
coupling of infrared photons and optical phonons at
the interface of polar materials. Even though theseevanescent waves have been widely exploited toenhance the cross-plane heat transport innanocavities (1), recent studies show that they canalso enhance significantly their in-plane heat flux. Ina vacuum cavity between two parallel plates of SiO2,
theory predicts that the maximum enhancement of
the radiative heat flux appears for a cavity width of 1
cm (2). This enhancement results from thehybridation of longitudinal guided modes and
SPhPs, as shown in Figure 1. The guided modes
appear in materials with a moderate absorption suchas silicon. Those modes can be thermally excitedand therefore enhance the outgoing flux.

Figure 1 - Vacuum cavity between
two polar materials supporting thein-plane propagation of SPhPs via
guided modes (blue lines) and Planck
radiation (red arrows).

MethodIn this work, we aim at providing an experimental proof to this enhancement driven by
SPhPs. First, the flux in silicon cavities with and without SiO2 layer has been studied bydirectional emissivity measurement, FTIR with integration sphere and FTIR + IR
microscope. As Si without SiO2 does not support the SPhPs propagation, thecomparison of both measurements is expected to provide a proof of concept of the
SPhPs contribution to the heat emission. Secondly, TRSTM measurements will be
performed to access the flux just above the cavity to reveal the the electromagnetic
field structure.
.
Perspectives

References

The measurement with FTIR + integration
sphere has shown promising results. In aneffort to confirm and understand thoseresults, several other measurements are
expected to
be done.
Moreover,simulations using the code SCUFF-EMM
will also be implemented.

1. Near-field Radiative Heat Transfer in ManyBody Systems. S.-A. Biehs and al Rev. Mod.
Phys. 93, 025009, 2021.
2. Resonant Polariton Thermal Transport Alonga Vacuum Gap. S. Volz and al. Phys. Rev.
Applied 18, L051003, 2022.

mcoral @ iis.u-tokyo.ac.jp
https://www.nlab.iis.u-tokyo.ac.jp

27

Measurements of Quartz Thermal
Diffusivity by the 3w Method up to 875 K.
Laurent Jalabert
Host Lab

Funding:
JST-CREST (S.Volz)

Nomura Lab

Keywords: Extreme temperature, thermal properties, 3-omega
method, thermal diffusivity and conductivity, reference sample
Context and Objectives

MethodElectrical measurements by contacting probe
tips with a sample, can be performed up to a
maximum
temperature
of
800K
using
conventional Vacuum Probe Station (VPS). But
nowadays, wide band gap semiconductors andsensors developed for harsh environment, needhigher temperature test to evaluate theirreliability. There is a need to engineer an
extreme temperature vacuum prober.

By combining two different know-hows, wecreated a prototype of vacuum probe station
operating routinely at 1200 K [2].
We tested the 3w/2w thermal method on areference sample (a-quartz from National
Metrology Institute of Japan) with calibrated
diffusivity measured by laser flash method up
to 800 K. The results are presented below.

Fig1 (left). Top view of the inside of the VPS during the measurement at 1200 K. Fig 2. Fitting
experimental data with the analytical model [3] from heater and sensor signals. Fig 3 (right). The
extracted thermal properties of a calibrated quartz diffusivity provided by NMIJ [3].

Results

The prototype could operate safely up to 875 K. We calculated the analytical solution of the 3omega method [3], and fit a set of 3w data to extract both the thermal conductivity and diffusivityof a quartz bulk sample. We found a good agreement with the calibrated data provided by NMIJ
using laser flash method.

Perspectives

Publications/References

We are now challenging suspended thin film
measurements at high temperature to compare
results obtained with optical TDTR, in order toconfirm the surface phonon polariton detection
at high temperature.

[1] Cahill, PRB, 35,8 (1987)[2] Jalabert et al., MRS (2022).
[3] Ordonez, Jalabert et al., JAP (2023)

jalabert @ iis.u-tokyo.ac.jp

https://www.nlab.iis.u-tokyo.ac.jp28

Nanophononics for Future Quantum
Technology.
Michele Diego
Hosted in

Nomura Lab

Keywords: nanophononics, nano-resonators,
optomechanics

Fundings:- Japan Science andTechnology Agency
Moonshot R&D- JSPS

Context and Objectives

Methods

Controlling the mechanical and opticalproperties of nano-objects is of paramountimportance in modern technology. By
structuring matter at the nanoscale, we candesign and characterize exotic devices toachieve specific functionalities.

Fabrication:- Electron beam lithography- Reactive-ion etching

As a main example, by periodically nanopatterning unit cells in a material, we
induce a modification in its photonic andphononic dispersion relations [1]. This
opens the doors to a variety of
applications, ranging from heat andacoustic transport [2] to optomechanicalcavities and quantum interfaces [3].

Characterization:- Brillouin light scattering spectroscopy- Vector network analyzer- Pump&probe optics
Design:- Finite element methods- Genetic algorithm optimization

Quantum telecommunication interface formed by a double hybrid nanoresonator of diamondembedding color defects and a piezoelectric material (AlN). By exciting mechanical modes indiamond, the system behaves as a spin qubit.
a. phonon dispersion of the hybrid unit cell and relative bandgap. b. fundamental resonant modeof the nanoresonator. c. simulated energy spectrum while tuning the excitation frequency.

References

Perspectives- Diamond optomechanical cavities forquantum networking[1] A. Balandin, JNN. 2005
[2] M. Nomura et al., Mater. Today Phys. 2022

- Introduction of automated methods toimprove the structural design (genetic
algorithm, machine learning, artificial
intelligence, etc.)[3] B. Kim et al., Phys. Rev. Appl. 2023

diego @ iis.u-tokyo.ac.jp

https://www.nlab.iis.u-tokyo.ac.jp

29

Heterostructure Cooler Fabrication
and Characterization.
Louis Grandvaux
Hosted in Hirakawa Lab
Keywords: Nanoscale cooling Heterostructure

Context and Objectives

MethodFor more than fifty years, the number of transistors inside achip has doubled every year following Moore’s law. This
results in a increase of power density inside chips leading
to lattice heating at more than 400K.

Cascade quantum wellstructure is made withlayers of GaAs and
GaAlxAs(1—x)
andischaracterizedbyphotoluminescence.

This problem can be solved using thermionic effect in aquantum well (QW) heterostructure where electrons
absorb thermal energy when jumping from the emitter tothe QW by phonon interaction [1].

Barrierheightiscontrolled by Al doping.

Cascade quantum cooler devices are investigated further.

Double quantum wellstructure (left)
Temperature in each
QW measured byphotoluminescence(right)Results

Several sample with different barrier heights were investigated. The best candidate canbe seen on the side figure with a tall barrier between the emitter and 1st QW. The tallbarrier acts as filter allowing only thermionic emission from QWs and preventing hot
electrons from emitter to heat the QWs.
From sample with two tall barriers, a depopulation of electrons happens around 0,5V
and temperature shows oscillation similar to what is observed in simulations [2].

Perspectives

References

Thermionic effect is a good candidate fornanoscale cooling device. However, more
samples need to be made in order to better
understand what happens in each QW andmatch simulation results.

[1] M. Bescond and K. Hirakawa, Phys.
Rev.Appl. 14, 2020

30

[2] G. Etesse et al., "A novel structure of
Cooling Nano-devices: The Quantum Cascade
Cooler."louis.grandvaux @ espci.fr

Novel Cooling Nano-Device:
The Quantum Cascade Cooler.
Guéric Etesse

Fundings:
Internal project 2023
ANR GELATO

Hosted in Hirakawa Lab
Keywords: Cooling, Quantum
heterostructure, Quantum transport

Context and Objectives

MethodWith the miniaturization of microelectronic
devices, self-heating effects are becoming
a rising problematic for which low-scaleheat
management
solutionsareinvestigated.

Quantum transport simulations using
NEGF formalism; Büttiker probes [2, 3]
Sample growth using molecular beam
epitaxy and PL measurements for electron
temperature determination.

The Quantum Cascade Cooler [1], amultiple quantum well structure whose
cooling capabilities rely on combinedresonant
tunnelingandthermionicemission filtering, shows promising results.

Results

Theoretical and experimental evidence ofanti-correlated oscillatory behavior of theelectron temperature in the quantum
wells.
Clear link established between the polar
optical phonon energy ℏω!" and theperiod of the oscillations.

Fig. 1: Electronic density of states of the
Quantum Cascade Cooler under a bias of 0.2 V.

Electron cooling of several tens of Kelvinachieved.

Perspectives
Experimental evaluation of the lattice
temperature.
Exploration of the cooling capabilities
upon optimization.
References[1] G. Etesse et. al. Phy. Rev. Appl. (accepted 2024)[2] M. Bescond et.al. Phy. Rev. Appl. 17, 014001 (2022)[3] A. Shastry et.al. Phy. Rev. B 94, 155433 (2016)

Fig. 2: Electron temperatures in the quantum
wells as a function of bias. Energy difference W
between the quantum wells ground state (blackline).

gueric.etesse @ im2np.fr

31

Hosted in

Quantum andMolecular Tech.
Axis

32

PEPR MoleculArXiv (2022-2029):

Massive Data Storage on DNA and Artificial Polymers.
Anthony Genot, Sona Roy, Paul
Bruand, Yannick Tauran,
Elias Boudjella, Robin Deteix,
HostedGwenaelin Bonfante, Axel Levy
Hosted in S.H Kim Lab

Keywords: DNA data storage, DNA synthesis,
DNA sequencing, microfluidic platform
Context
Data storage is crucial in our society: exabytes of

Objectives and Methods

data are generated every year in France(communication, culture, finance, politics,

Write 1 unique bit per second (100x faster thancurrently)

industries, etc.) and the “digital universe” willgrow to over 175 zettabytes (1021) in 2025.
Current data warehouses use electronic,
magnetic and optical media, which have limited
durability and density. DNA, on the other hand,is extremely dense and stable, but it is currently
costly and slow to synthetize.

Write 10GB of data in 24 hours with off-theshelf parallelization
How?
Making synthesis fast and scalable (WP1&3)
Making storage efficient and secure (WP2)
Making DNA storage practical (WP4)

PEPR MoleculArXiv at a glance: an interdisciplinary project, LAAS, LMI● 20M€ over 84 months● LIMMS is at the forefront of experimental implementation.
● 16 French laboratories, including 6 flagship labs
Publications/References

Perspectives[1] Okumura et al., Nature, 2022

● Maturation of technology● Collaboration with FR and JAP industrials● Application to Japanese maching funds.

[2] Genot et al., Nature Chemistry, 2016
[3] Lobato et al., Nature Chemical Engineering, 2024

genot @ iis.u-tokyo.ac.jp
www.shkimlab.iis.u-tokyo.ac.jp33Additive Manufacturing to Control
DNA Hydrogels Spatial Organization.
Audrey Cochard, Vincent Salles, Yannick Tauran
Hosted in SH Kim Lab / BJ Kim Lab

Funding:
Internal project 2023

Keywords: DNA nanotechnology, DNA hydrogels, 3D printing.

Context and Objectives

MethodDNA hydrogels
tunableandmaterials.

To build DNA hydrogels, we use threecomplementary DNA strands able to form Ymotifs [1]. Through sticky-end interactions and Ymotifs binding DNA hydrogels are formed byphase separation (Fig. 1)
Molding methods wereused in recent papers
to form DNA gels withpredefined shapes [2].
Here,additive
manufacturing is used
to have a more precise
control (Fig. 2).

are interestingbiocompatible

Controlling the spatial organizationof DNA hydrogels would be aninteresting asset and would haveapplications in tissue engineering,artificial organs… However, itremains a challenge.
In this project, we combine theexpertises of the SH Kim Lab in DNA
hydrogels design and of BJ Kim Lab
in 3D printing to develop a methodto spatially control the organizationof DNA hydrogels.

Figure 1: Formation of
DNA hydrogels

Results
Predefined structures were obtained
manufacturing of DNA hydrogels.

throughadditive

Figure 2: Experimental setup to print a
DNA hydrogel with a predefined structure

Perspectives

References

We are currently working on improving thesystem to be able to create finer structures.

[1] Y. Sato et al., Sci. Adv. 2020[2] J. Lee et al., Nature Nanotechnology, 2012

acochard @ iis.u-tokyo.ac.jp34

Thermodynamic and Rheological
Analysis of DNA Hydrogels.
Hajar Ajiyel

Fundings:
Internal project 2023
Internal project 2022
CNRS PhD grant

Hosted in SH Kim Lab
Keywords: DNA nanotechnology, design,calorimetry, rheology, soft matter

Context and Objectives

MethodThis project is a collaboration between labs
in France (Grenoble and Lyon) and Tokyo.
While state of the art research has primarily
focused on the formation of DNA
hydrogels [1], less attention has been paid
to understanding their thermodynamic andrheological properties in relation to theirsequence design. Our objective is tobridge this gap by investigating how thecharacteristics of DNA hydrogels relate totheir design, conducting a comprehensive
study across various scales. We anticipate
that the insights gained from this study will
have broad applications in fields such as
therapeutics and biosensing.

DesignDNAsequencesforminghydrogels, and study them with multiple
techniques in calorimetry, and passive
and active rheology

Formation of a DNA hydrogel from
Y- shaped nanostars [2]Results
An excess heat is generated when a DNA hydrogel is formed. Changing the length of
the sticky end in the nanostars introduces different viscoelastic behaviors in the gel.

Micropipette aspiration experiment on different
DNA hydrogel designs

Specific heat of DNA hydrogel vs DNA nanostar

Perspectives

References

Measure thermodynamic and rheologicalproperties of DNA hydrogels with multiple
techniques, to get a more comprehensive
perspective of their behavior.

[1] Y. Sato et.al., Sci. Adv. 2020
[2] F. Li et.al., Progress in Polymer Science.
2019

hajar.ajiyel @ neel.cnrs.fr

35

Ballistic Brownian Motion of
Nanoconfined DNA.
Nicolas Clément

Fundings:
EU Attract Unicorn Dx
ANR SIBI

Hosted in S.H. Kim Lab
Keywords: Charge transfer, Electrodes,Genetics,
Mathematical methods, Nanoconfinement

Context and Objectives

MethodTheoreticaltreatmentsofpolymerdynamics in liquid generally start with thebasic assumption that motion at thesmallest scale is heavily overdamped;
therefore, inertia can be neglected. We
report on the Brownian motion of tethered
DNA under nanoconfinement, which wasanalyzed by molecular dynamics simulationand nanoelectrochemistry-based singleelectron shuttle experiments.

We introduce a new code (QBIOL)
combining molecular dynamics of DNA(OxDNA) and quantum processes withstochastic electron transfer to a redox
marker. These simulations are used toreproduce electrochemical experiments
performed
withan
AFM-SECM
microscope with precise nanogap.

Results
Our results show a transition into the ballistic Brownian motion regime for short DNA in
sub-5 nm gaps, with quality coefficients as high as 2 for double-stranded DNA, an effectmainly attributed to a drastic increase in stiffness. The possibility for DNA to enter theunderdamped regime could have profound implications on our understanding of theenergetics of biomolecular engines such as the replication machinery, which operates innanocavities that are a few nanometers wide [1,2].

Schematic representation of the system
under study. A tethered ds-DNA
nanoconfined between two electrodes.
The heat map represents the position of
the redox marker.

a Schematic representation of the experimental
setup. b Experimental result of current as afunction of the gap for ssDNA and dsDNA.

Perspectives

References

Qbiol is being transferred via aprematuration program of CNRS forsoftwares. We plan to further investigate
this ballistic Brownian motion regime via
shot noise measurements.

[1] I. Madrid, Z. Zheng, C. Gerbelot, A. Fujiwara, S. Li,
S. Grall, K. Nishiguchi, S.-H. Kim, A. Chovin, C.
Demaille, N. Clement, ACS Nano 17, 17031 (2023)[2] Z. Zheng, S. Grall, S.-H. Kim, A. Chovin, N.
Clement*, and C. Demaille*, J.Am.Chem.Soc. 146,
6094 (2024)

nicolas.clement @ cnrs.fr

36

Towards Multiplexed Electrochemical
Single-cell Aptasensor Array.
Fundings :Shuo Li
Host Lab

JSPS, NTT, EU ATTRACT 2

S. H. Kim Lab

Collaborators:, N. Clément, S. Grall, S. H. Kim, H. Y. Dai (IIS, Utokyo), C. Lagadec (Inserm), Y. Coffinier,F. Cléri (IEMN), L. Jalabert, K. Nishiguchi, A. Fujiwara (NTT corporation), C. Demaille (CNRS, LEM)

Keywords: Nanobioelectrochemistry, cancer cell, Micro/Nano fabrication

Context and Objectives
Electrochemical (EC) aptasensor is very attractive fordetecting and monitoring interactions with biologicalobjects because of the high sensitivity, easy operation,
low-cost, and benefit from ultimate scaling.
By using redox-labelled EC aptasensor, it enables toenvision measurements and theory at the single-virus
scale as well as statistical analysis on larger objects suchas circulating tumor cells (CTCs). Here, a novel singlecell EC aptasensor array was introduced and opens newopportunities for ultra-sensitivity and selectivity of earlycancer diagnosis and therapy.
ab-Fabricating and achieving single-cell EC aptasensor
array device. (All of the fabrication processes isdeveloped in Utokyo, Nanostructure is obtained byusing high resolution e-beam lithography.)-The single-cell EC aptasensor was first time
performed. A final sensor configuration is a nanoarraywith multiplexed electrodes, towards multiple signal
analysis at single-cell level

Reduce fraction of Fcd
HSQ nanopillars

0

rra
y

Profile

-10
-5
0
5
10
15
20

Z (nm)

Auafi l e

20
15
10
5
0
-5
1

2

3

4

5

Length (7m)

6

7

8

9

0

Counts10 20 30 40 50

Width of the interdigitatedelectrodes: ~1.7 μm

19.7 nm/S
i

Pro
Height (nm)

l
ne
an
ch
cro SUi
M
8
Flo
Sil Mic
HSQ nanopillars
w
ico rone well aGSU-8 microwells
aske rrayt
Au electrode

Grafting aptamers-A 𝜇m-scale gold surface (Au/Si) array was fabricatedto graft ferrocene modified aptamers (SYL3C-Fc) tocheck the signal.

Target cell

Non-target cell

No reduce fraction of FccMethods and Results

Cells loading

Figure 1. Principle of the single-cell EC aptasensor array.

Figure 2. CV results toshow the selectivity of thedevice.

Figure 3. Photo of themultiplexed
electrodes.

Perspectives-This novel single-cell EC aptasensor offering unprecedented statistical analysis of CTC in clinicalsettings.
-The next gerneration device would be realizing multi-electrodes for multi-target detetion and 10
nm scale nanodots array biosensors for single molecule-single cell analysis.

Publications/Reference

shuoli06 @ iis.u-tokyo.ac.jp[1] S. Li et al. Biosens. Bioelectron. 216, 114643, (2022).
[2] S. Li et al. ACS Sens. 8(8), 2921 (2023).
[3] K. Chennit et al. Nano. Res. 1-7. https://doi.org/10.1007/s12274-022-5137-1, (2023).

37

www.shkimlab.iis.u-tokyo.ac.jp

Nanoelectrochemical Biosensors
Simulation.
Fundings :ANR SIBI, NTT,EU ATRRACT

Simon Grall
Host Lab

S.H Kim Lab

Collaborators: :, N. Clément, S. H. Kim, S. Li (IIS, Utokyo), L. Jalabert (LIMMS), K. Nishiguchi, A. Fujiwara (NTT
corporation), C. Demaille (CNRS, LEM), T. Fukuba (JAMSTEC).

Keywords: Nanoelectrochemistry, shot noise, high-frequency, environmental sensing,energy harvestingContext and Objectives

Methods

The concept of electrochemical shot-noise [1] opens up
potential avenues for enhancing electrochemicalsensors, offering promising prospects for nanoscalebiosensor measurements. Leveraging the current
understanding of GHz electrochemistry [2-3] and therecent advancements demonstrating low reorganizationenergy in confined polymers [4], we are optimistic about
the possibility of creating devices like single molecule
sensors and molecular rectennas operating at opticalfrequencies.

To better fathom the limit of single-entity
measurement foreseen thanks to noise and GHz
measurements, we are developing a simulation
framework to simulate stochastic fluctuation of charges
for one-electrode electrochemical systems in the ongoing project QBIOL.
GHz nanoelectrochemistry allows for
impedance spectroscopy at the nanoscale

Electrochemical shot noise

One-electrodeelectro-chemical
simulation

Results

QBIOL already helped to solve the riddle of apparent
slow DNA diffusion with a two electrodes framework[5], and is now on track to account for stochastic
fluctuation in the time-dependant one-electrode case.
This work allows to simulate electrochemicalmeasurement
techniques(squarewave,
CV,chronoamperometry) of single molecules and help
understand their stochastic behavior in the frequency
domain (noise).
(a) FcC11SH SAM on gold. (b) CV of a FcC11SH SAM on gold.
(c) Noise spectra measured at 0.014 mV/s (d) Noise versus
potential at 10 Hz.

Perspectives
It already provides useful insights for experimentalists
developping DNA biosensors. More work is needed tosimulate a wider variety of molecules and fully develop
analytical models for the simulated noises. In the
future, it will provides a digital experiment platform
able to simulates devices from nano-biosensors tomolecular rectennas.

Publications/Reference
These two double-stranded (T sequences) have different
lengths. They carry the same electrochemical marker. Though
they show similar currents during a chronoamperometricmeasurement (a), they exhibit different noise signature (b).

[1] S. Grall et al, Phys. Rev. Lett., 2023
[2] J. Trasobares et al, Nat Commun, 2016[3] S. Grall et al, Small, 2021.
[4] I. Madrid et al, ACS Nano, 2023
[5] Z. Zheng et al, JACS 2024

Contact: sgrall @ iis.u-tokyo.ac.jp

www.shkimlab.iis.u-tokyo.ac.jp

38

Versatile Electrospun Nanomesh
for Robust Skin Electrodes.
Dorina T. Papanastasiou

Funding: JSPS
Postdoctoral Fellowship for
Research in Japan(Standard)

Hosted in Someya Lab
Keywords: e-skin, smart textiles, soft-rigid
interconnection, mechanical properties

Context and Objectives

MethodSkin is the largest organ of human body withelectrical properties of great interest for alarge variety of applications[1]. Recordingthese properties can provide information for
the thermoregulation or other stimuli tofurther diagnose the skin condition, as well as
psychophysiological state[2]. Despite theextended biomedical research, there areunclearaspects
requiring
long-termmonitoring that cannot be achieved using
conventional electrodes.

Previous works of Someya Lab havedemonstrated state-of-art, ultra-thin,skin-conformable, and bio-compatible
electrodes, using scalable deposition
techniques, i.e., organic electrospun
nanofibers [4].

Skin electronics advances are remarkable,
however there are remaining issues thathinder the integration of novel electrodes incommercial skin devices. One of the mostimportant is the interconnection between soft,ultra-thin electrodes and data acquisition hardwiring. [3]Results

The present project has been
focusing on remaining interface issues
between soft and rigid parts, and theintegration of nanomesh electrodes intextile-based substrates. Developing
robustinterconnections
cancontribute to the next-generation
wearable devices with personalized
healthcare features [5].
Nanomesh electrodes

Conventional electrodes

References[1] Kim et al., Adv. Funct. Mater. (2021), 31, 2009602[2] Tronstad et al., Physiol. Meas. (2022), 43, 02TR01[3] Jang et al., Nat Commun, (2022), 13, 6604
[4] Miyamoto et al., Adv. Healthcare Mater. (2022), 11, 2102425[5] Papanastasiou et al., article under preparation

d.t.papanastasiou @ gmail.com

39

A Camera System for Real-Time Monitoring
Continuous Fluorescence Changes.
Yui Sasaki & L. Jalabert
Hosted in Minami Lab & Nomura Lab
Keywords: Fluorescent materials, Real-timemonitoring, Imaging analysis

Context and Objectives

Research background: Design of solidstate fluorescent materials with uniqueproperties

Funding:
Internal project2023

MethodTime-dependent optical changes
10 s

50 s

90 s

100 s This study

Component 1 Component 2

A camera system for the investigation oftime- and temperature-dependent
fluorescence properties
Emissionquantum yield3%

Solid-phase
synthesis

Data acquisition
and analysis

Emissionquantum yield
18%

UV light

The obtained products show different
fluorescent color depending on chemical
structures and solvents.

Results

CameraSelection of points

Peltier plate
SampleObtained pixel intensity

Camera systemDataanalysis

The developed camera system allows real-timemonitoring of continuous fluorescence changes.

Perspectives
Intensity

Real-time monitoring results

Time / sCollaboration with
S.Chevalier group(U-Bordeaux)foranalysis of kinetics

sayui @ iis.u-tokyo.ac.jp

40

Discovery andinvestigation of
new phenomenaof functional
materials

jalabert @ iis.u-tokyo.ac.jp

Hosted in

Bio
Axis

41

Spiking Neural Network for Unsupervised
Spike Sorting in Real-Time on FPGA.
Jérémy Cheslet
Hosted in Ikeuchi Lab
Keywords: Spike sorting, SNN, STDP, FPGA,
real-time, HD-MEA

Fundings:
ANR BRAIN-NetUBGRS 2.0
(ANR-20-SFRI-0001)

ID
phot
o

Context and Objectives

Results

Neural prosthetics are potential treatments
for neurodegenerative diseases, but it
requires deep understanding of neural
populations [1].

The SNN sorts with an accuracy on parwith offline methods after a few minutes of
unsupervised training.

Spike sorting is an operation that extract
important features from neural-recordings
while considerably reducing the amount ofdata to save.

It processes in real-time at low-power due
to its low hardware consumption.

However, low-power, accurate, real-time
spike sorting is still a challenge [1].

Fig.1 – Principle of spike sorting: find which
neurons are spiking in the neuronal culture.

MethodInspired from [2], we implemented a 3layer SNN on FPGA. [3] shows apreliminary
versionfor
low-cost
spikes/bursts detection.

Fig.3 – Results on AMD K26 SOM

Perspectives
Use HD-MEA data to further improve thespike sorting accuracy.
Perform bio-hybrid experiments.

References[1] Zhang et al, J. Neural Eng., 2023
[2] Bernert et al, Int J Neural Syst., 2018
[3] Cheslet et al, IEEE BioCAS, 2023

jeremy.cheslet @ u-bordeaux.fr

Fig.2 - Structure of the SNN

42

Understanding Human Brain Mechanisms
Through Organoid Circuit Modeling.
Tomoya Duenki

Fundings:
Spring GX Fellowship
ANRI Fellowship

Hosted in Ikeuchi Lab
Keywords: Neuroengineering, neuralorganoids, human pluripotent stem cell
derived neuron, optogenetics

Context and Objectives

Results

Limited access to a living human brain
tissue has made it very difficult to study it.
Recent advances in stem cell biology has
led to the discovery of neural organoids,
which are artificially grown miniature organlike tissues resembling the brain. Thismodel recapitulates key features of thebrain and has opened up new possibilities
to study development, function anddysfunction of human brain cells in a dish.

We show that :- Organoids in microfluidic devices canconnect to each other via axon bundles.
- Connection between organoids show
signal exchange and propagation.

Fig. 1: Image of connected neural organoid in a
microfluidic device.

MethodI create custom-made microfluidic devices
that can guide axonal outgrowth ofneurons between organoids. By doing so, I
can control neural circuit formation,connect two neural organoids with a thickaxon bundle. The connected organoids areplated on electrode arrays which allows me
to monitor the electrical activity of theliving neurons in the organoid. With
optogenetic stimulations, I can control
neural activity of cells and study responseof neurons and signal propagation within
and between organoids.

Fig. 2: Connected organoid on an electrodearray. Optogenetic stimulation of the leftorganoid induces a burst. The initiated burst
propagates to the connected right organoid,
which also starts to burst with a time delay.

Perspectives
We connect different tissues and create
circuits present in our body in order tobuild new platforms that can be used to
study mechanisms of our nervous system.
References[1] Osaki, Duenki, Chow et al., Nat. Commun., 2024
[2] Ikegami, Duenki et al., Front. Bioeng. Biotechnol.,2024

duenkit @ iis.u-tokyo.ac.jp

43Deciphering Neuron/ Breast Cancer Cell
Interactions to Understand Metastasis.
Robert Alain Toillon
Hosted in Ikeuchi Lab

Funding:
Internal project 2023

Keywords: Microdevice, neuron, breast cancer

Context and Objectives

MethodDespite progress in the management ofbreast cancer, the development ofmetastases has a poorer prognosis [1]. It istherefore necessary to develop systems forstudying the behavior of cancer cells
during the development of metastases,
and in particular the interactions between
cancer cells and their environment [2]. In
collaboration with Professor Ikeuchi'slaboratory(Japan),the
CANTHERlaboratory (France) is seeking to set up asystem for studying breast cancer cells andneurons in order to study the relationshipbetween the 2 cell types.

We used custom-designed compartmentalized chamber systems to study
chemotaxis
between
triple-negative
breast cancer cells and neurons. In thissystem, we were also able to study axonal
growth and changes in membranepotential in neuronal cells as a result of
their excitability.
neuroneCancer cells

A compartmentalzed chamber

Results

Under these conditions, we were able to observe that neurotrophin receptor overexpressing- cancer
cells have an increased capacity to interact with neurons and are able to migrate along axons(Figure 1). In addition, we were able to demonstrate activation of intracellular signaling in cancer
cells by FRET experiments using RhoA biosensors [3,4].
Figure 2: Activationof RhoA measured byFret biosensor in
MDA-MB-231 cells inpresence of neuron
conditioned media(NCM)

Phalloïdine : MDA-MB-231 TrkA, Tuj1 : axon
Figure 1: Migration of triple-negative breast cancer
cells (MDA-MB-231) along the axon.

+ NCM

+ NCM

Perspectives

References

After highlighting the phenotypes induced bycancer cells in neurons and vice versa, we aregoing to study the importance of these in themechanisms of metastasis in order to find either
inhibitors that would act against metastatic
development or predictive markers of metastasis,
enabling better monitoring of patients at risk.

[1] Deluche et al., Eur J Cancer, 2020.

yikeuchi @ iis.u-tokyo.ac.jp

44[2] Cicero et al., Exp. Hemat. & oncol, 2023.
[3] Pertz et al., Nature, 2006.
[4] Trouvilliez et al, JECCR, 2022.

robert.toillon @ univ-lille.fr

Microstructuring of Resorbable Scaffolds
for Vascularized in-vitro 3D Tissues.
Vincent Salles
Hosted in BJ Kim Lab
Keywords: Direct-write electrospinning, resorbable and functional
scaffolds, tissue engineering

Context and Objectives

Results

The proposed approach consists increating in vitro, using resorbablematerials, an architecture of interconnectedvessels and micro-vessels connected to a
microfluidic system to continuously feed
the vascular system via which it will bepossible to feed the cells positioned
around. On a long term, complex
architectures could be implanted andsutured to the patient’s vascular system.

A series of novel resorbable architectures
were developed to prepare permeable
sacrificial scaffolds. On the fabrication
point of view, several useful patterns havealready been produced (in 2D and 3D).
These structures were tested separately
with endothelial cells and neuronal cells
to investigate the ability to produce newblood vessels and neural tissue,
respectively. Different tests are used to
optimize the preparation of the scaffold
and the cell culture conditions. These
preliminary results were obtained by
using
PCL
(Polycaprolactone)asresorbable polymer.

MethodThe fabrication process of the scaffold isbased on a combination of a 3D printerand an electric field applied between anozzle and a printing stage. For thisproject, a peculiar machine was designed
and supplied. This project is carried out incollaboration with 3 host-labs, as shown
below.

Organoids in a grid ofresorbable polymer

Vessel of endothelial
cells through the grid

Perspectives
Gradually increase the complexity ofcellular organisation.

Direct-write electrospinning

References[1] L. Bourdon et al.,J. Funct. Biomater. 2023,
14, 263[2] C. Xu et al., Biomed. Microdevices 2023,
25, 32Involved collaborators

vsalles @ iis.u-tokyo.ac.jp

45

A Biohybrid Neurocardiac Platform
for Electroceutical Approach.
Pierre-Marie Faure

Fundings:
Fondation Sasakawa
Région Nouvelle-Aquitaine

Hosted in Tixier-Mita Lab
Keywords: Cardiomyocyte, Real-time,
Biohybrid, FPGA

Context and Objectives

MethodTo investigate the neurocardiac axis involved in
cardiovascular diseases, we are developing anelectronic platform that reproduce theinteraction between the brain and the heart inreal-time.

We target our implementation on FPGA toachieve real-time necessary for biohybrid
applications. The chosen models are biologicalaccurate to obtain a realistic description of
involved phenomenon.
Layers of theplatform, the input
can be artificial
neuronal networkor biologicalneurons while
output is a
cardiomyocyte
culture.

Description ofneurocardiac axis

Results
We achieved to develop the sinoatrial (SA) node part on FPGA and using it to stimulate
cardiomyocytes and trigger their beatings. In addition, the autonomic nervous system layer is able
to interact with SA Node.

Output signal generated in real-time

Implemented model of Maltsev-Lakatta on FPGA

References

Perspectives
The different parts of our platform aredeveloped. The next step is their combination toachieve the platform. After that, we aim to use itinexperiments
toconnect
biologicalcardiomyocyte with neurons culture.

[1]

Maltsev & Lakatta, American Journal of
Physiology-Heart and Circulatory Physiology, 2009[2]Šćepanović,
Massachusetts
Technology, 2011[3]

Faure P-M., Tixier-Mita A., Lévi T., 29th
AROB’2024, Beppu, Japan, Jan. 24-26 2024.

Instituteofpierre-marie.faure @ u-bordeaux.fr

46

Automatization of 2D Bio-Impedance
and Cardiomyocyte Activity Investigation.
Alexis Mallet, Juliette Flamant, Romane
Kessedjian & Thomas Menier
Hosted in: Tixier-Mita Lab
Keywords: Cardiomyocyte, bio-impedance,
Nifedipine, PLL coating

Context and Objectives

Methods & Results

Cardiovascular diseases are the first cause ofdeath in the world. In order to investigate further
heart diseases and find new treatments, it isessential to study the mechanism behind. Given
the constraints on in vivo experiments and theethical considerations involved, there is acompelling rationale for exploring in vitro
approaches. The primary objective of theresearch presented here is to develop a platform
to measure the multiple electrical andbiochemical parameters involved in in-vitro heartcell culture. Here, automatization of 2D bioimpedance measurement to monitor cell culture
and cell activity control are presented.

The platform consists in an active matrix of
microelectrodes controlled individually byswitch transistors, and based on Thin-FilmTransistor technology.
Thanks to thetransparency and multitude of microelectrodes,
simultaneous
opticalandelectricalmeasurements can be performed. The
microelectrodes are controlled by a control
card.
Bio-impedance
measurements
isautomatized by a Python program. PLL coating
is used to improvement cardiomyocyte cellattachment. Then, experiments of control ofcell activity using Nifedipine chemical is
performed. Ca2+ is the link between electricalsignals inheart and contractionofcardiomyocytes. Nifedipine is a Ca2+ channel
blocker which can modify cell contraction.
Improvement of cell attachment with coating

Control card
No coating

TFT Platform
Computer

OUTPUT

Generator- + + +PolyLL coating

Cell activity control with Nifedipine
Calcium imaging (Fluo-4)

MUX

Nifedipine

Lock-in
AMP

Automatisation of 2D bioimpedance measurements

Noamplitude of cellWith
Nifedipine Nifedipine contraction with time.

Perspectives

References

Bio-impedance measurement will permit tomonitor cell culture, and possibly to measure in
real-time the contraction of cells. It will be
confirmed by simultaneous optical observationand electrophysiology.

[1] Menier T. et al, “Open-source Live-Tracking
Softwarefor
Cardiomyocyte
Cells
Analyses”, Sensor Symposium’2023, Nov.
6-9 2023.

47

agnes @ iis.u-tokyo.ac.jp

Compact Microscope for Long Term
Experiments.
Alex Dufour, Théo Foschia
Hosted in Tixier-Mita Lab
Keywords: Raspberry, arduino, real-time observation,dielectrophoresis

Context and Objectives

MethodIncubators reproduce the optimal conditions
for in-vitro cell culture and limits contamination.
However, for practical reasons, cell culture
analyses are usually performed outside the
incubator, which modifies the cell environment.
This is especially true for long termmeasurements. Here we propose to develop a
compact microscope platform which will permit
at the same time optical and electricalmeasurements (impedance, electrophysiology,
dielectrophoresis).

The compact microscope platform is inspired
from [1]. It is composed of a 100X to 600X lens
attached to a Raspberry Pi Camera, an XY
stage moved by stepping motors and an LED
light. They are all controled by a Rapberry Pi, in
which a custom Python program has been
implemented. It will be combined with amultiplexer system able to select various
electrical measurement methods.

Results

10μm
microbeads
placed on aThin-FilmTransistor
paltform

A first prototype of the microscope has beenrealized. It was applied to dielectrophoresis withmicrobeads. Further development is next
necessary for long term compatibility with thehigh humidity of the incubator.

Dielectrophoresis byapplying an AC
signal: 2V,
10kHz

500μm

500μm

Perspectives
This project is a key element of a wider project
which purpose is to create an in-vitro model ofthe brain-heart system. Interactions at the celland tissue level will be investigated especiallywhen heart disease are mimicked. For that
purpose a multimodal sensing platform will be
realized, combining optical and multimodal
electrical sensing.

References[1] IBM MicroscoPy:
https://github.com/IBM/Microscopy[2] Eiler A-C., IEEE TED, Vol 68(4), April 2021.

agnes @ iis.u-tokyo.ac.jp48

Microvessel-On-Chip for the Study ofIntratissue Solute Transport.
Daniel AlcaideFundings:
Hosted in Matsunaga Lab
WINGS – QSTEP
Keywords: Microfluidics, Vasculature-on-chip, University of Tokyo
Microvessel (MV), Permeability, Hydrogel,Brain, Glymphatic system

Context and Objectives

MethodThe mechanisms through which neural waste
and other toxic molecules are removed from thebrain is not fully understood due to the lack oflymphatic vasculature in the brain. The current
model, named glymphatic model, proposes
arterial pulsation fluid motors that create thecerebrospinal fluid flow removing the waste fromthe tissue.

We fabricated a microfluidic device that hosts
two in vitro MVs, one artery and one vein,suspended in a hydrogel. These MVs can beconnected to a pressure controlling device togenerate customizable arterial pulsations.

We aim to replicate the basic elements of theglymphatic model in vitro to study how thearterial pulsations can create such flows in abrain-like soft material.

Weobservedhowdifferent settings ofperiodic pressure pushand move fluorescentmolecules in between
the artery and vein
Figure 1 – Picture of the microfluidic device

Results
We observed the displacement of fluorescentdextran molecules due to MV pulsation.
Different frequency and pulsation amplitude
were tested. However, MV deformation andpermeability seem to have a stronger relation
to the type of fluid movement observed in thedevice. Brain-like, low permeability MV, inducea deformation-driven recirculation, likely
relevant to the glymphatic model scope.

Figure 2 – Fluorescence picture of middle
area of the device the two MV and FITCDextran displaced by pulsations of thebottom MV.

Perspectives

References

This device allows virtually for the visualization ofinterstitial fluid recirculation of virtually anyorgan. We look forward to expand its application
further than brain parenchymal transport.

[1] - Iliff J. et al. Science Translational
Medicine, 2012.
[2] - Soden P. et al. Advanced Biology, 2022.

daniel-a @ iis.u-tokyo.ac.jp49

Physical Properties of an Artificial
Microvessel System.
Baptiste Alric

Fundings:
IIS
JSPS fellowship

Hosted in Matsunaga Lab
Keywords: Microfabrication, Organoid,
3D-cells culture, Physical properties
quantification

Context and Objectives

MethodOur project aims to improve our understandingof the physical properties of artificial
microvessels
and
their
surrounding
microenvironment.

In our research, we use homemade microfluidic
chips to fabricate our microvessels Fig1[1]. To
achieve this, we use acupuncture needles tocreate channels within hydrogels - a type ofprotein-based gel consisting of 90% water - inwhich we can cultivate our endothelial cells in achannel shape. After establishing our system,
we use various methods to extract the physicalproperties of these vessels[2,3].

Our goal is to develop more accurate organ-ona-chip models. To realize that we are working
closely with partners in both Japan and France
to establish various cellular models and todevelop unique methods to qualify these
physical properties.

1D-stiffness (Pa)Results

3000 Compression

Tension

2000
1000
0
-1000

-500

0

500

Pm(Pa)

200 µm

Fig.1 Artificial microvessel of HUVECs
imaged by confocal microscope, the cell
membrane is green, the cytoplasm isred, and the nucleus is blue.

1000

Permeability (x10!"𝑚#)And we are showing that those physicalproperties are particularly important in the
microvessels physiology.
20

Compression

Tension

15
10
5
-1000

-500

0

500

1000

Pm(Pa)

Fig.2 Physical properties extracted from different
acellular hydrogels using a pressure measurement assay
combined with a mathematical model [2]. These graphs
show a clear asymmetry in the response of the hydrogels
between compressive stress (negative pressure) andtensile stress (positive pressure).

Perspectives

References

These models not only facilitate a deeper
understanding of various biological phenomena,
but also aid in the development of drug
screening processes to identify effective
treatments for specific diseases.

[1] Pauty et al, 2018., EBioMed. 2018
[2] Cacheux et al ., Sci. Adv. 2023
[3] Cacheux et al ., ISci. 2023

balric @ g.ecc.u-tokyo.ac.jp50

SOI-CMOS Large-Scale Integrated
Circuit for Particle Detection.
Anne-Claire Eiler
Hosted in Mita Lab
Keywords: CMOS, silicon on insulator (SOI),
large-scale integrated (LSI), coulter counter

ID
phot
o

Fundings:
JST CREST
JSPS Core-to-Core
MEXT X-nics
ARIM

Context and Objectives

MethodLarge-scale integrated microchip for coultermeasurement, using the SOI technology forfaster switching and better performance:- array of 320 electrodes- electrode size: 44.0 µm x 36.4 µm- sensing array: ~1.02 mm x 0.81 mm- pitch: 51 µm~386 electrodes/mm2

Post-processing on matrices of electrodes
controlled by transistors integrated by LSI in
open cleanroom facility.

Foundry
company
Multi chips

Takedaclean room
LSI wafers

Microchip provided byan LSI foundry company

Post-processed
functional devices
à LSI chip must be post-processible
à want to know what can be done with it

Microchip from design, fabrication, and postprocessing for desired applications

Post-processing workflow for fabrication of acoulter counter: lapping, polishing, top side
etching, deposition, back side etching

Results

Idmax à 1.0 mA
Vdmax à 1.8 V
gmmax à 1.0 mS
VTH à ~0.5 V

Post-process and characterization:

Microchip
after postprocessing(a) Top side process(b) 1.6 cm
Post-process on the LSI microchip:a) top side etching of 3 um holes;b) fully processed microchipSize of transistor = 5.0 µm

(a)

(b)

è 200 µA/µm
è 200 µS/µm

Electrical characterization of the integrated transistors:a) drain current vs gate voltage with logarithmic scale;b) electrical parameters of the transistors

Perspectives

References

Fabrication of a fully functional LSI microchip tobe used as a counter coulter. Another fabrication
could involve the development of an electrodearray for electrophysiological measurements.

[1] Y. Mita et al., Japanese Journal of Applied
Physics 56, 06GA03, 2017[2] Y. Chen et al., Sensors and Actuators B:
Chemical 213, 375-381, 2015

anne@if.t.u-tokyo.ac.jp

51

Investigation of the Metabolic Syndrome
Development Using Organ On Chip
Technologies
Fundings:

Eric Leclerc
Host Lab

Sakai, Nishikawa lab

Keywords: induced pluripotent stem cells, Organon-a-chip, Metabolic syndrome

Context and Objectives
Metabolic Syndrome (MSy) has a prevalence ranging to
24.6–34.7% of the population in Japan in early 2000s
and up to 36% in European countries. MSy is a complex
disorder involving several tissues and organs and theirinteractions resulting in diabetes (individuals with MSy
are 5 times more likely to develop type 2 diabetes)
obesity, non-alcoholic fatty liver disorder (NAFLD has aprevalence between 50% to 90% in obese patients andin 30% to 74% in MSy patients), cardiac failure (up to49%), blindness . In this project, we will develop onorgan-on-chip technology to address these key
challenges, to move a step closer towards
understanding, diagnostics and therapies of metabolic
syndrome.

JSPS 22H03934;
JPJSCCA20190006;
ANR 23-CE18-003503;
Chaire UTC/DOT

Results
We progressed on the liver and pancreas modules.
Human-induced Pluripotent Stem Cells (hiPSCs)derived Liver Sinusoidal Endothelial Cells (LSECs),
Hepatic stellate cells (HSCs), Hepatocytes-Like Cells(HLCs) were cultured and matured in a microfluidic
environment. Liver maturation on chip was observed
and subpopulation identification was performed (Fig 2).

Fig 2: Liver on chip (green albumin, red CK19, blue PECAM1)
and single sequencing clustering (Scheidecker et al., 2024)

Methods
We propose toThen, we proposed a protocol to differentiate hiPSCs
into pancreatic-like-cells (created in 3D micro
To build an innovant bio artificial organ researchhoneycombs). The protocol led to the development ofstrategy in which human cell model will be used tospheroids producing C-peptide and containing cells
generate a relevant systemic MSy model (Fig 1)
positive to insulin and glucagon. Sequencing revealed
To establish a specific metabolic syndrome disease complex heterogenous bi-hormonal profiles (Fig 3)
model with which we will track the heterogeneity andthe kinetics of the disorders thanks to the bioartificialorgan human physiopathology
To identify biomarkers and therapeutic solutions
regarding the disease specificity using multi omic
technology, advanced sensors and clinical data
MSy dysfunctions

Liver on chipLiver

FFA accumulation
Adipocytokines

Liver disorders due to- Too high FFA accumulation- High insulin stimulation

liver adipocytes on
chip
Positive energybalanceInsulin resistance
Inflammation
NAFLD

Adipocytes

FFA uptake
Energy substrates

Optimised full OOC
solutionsliver-pancreas on
chip
Insulin

Adipocytes on chipMSy dysfunctions
MSy dysfunctions
Adipocytes
disorders

Adipocytes pancreas
on chip
Insulin resistance
FFA accumulation
adipocytokines
inflammation

Pancreas
Pancreas on chip

Pancreas disorders:
T2 Diabetes
Insulin resistancePancreas steatosis(FFA accumulation)

Fig 3: Beta like cells in honeycombs and bihormonal patterns(Morisseau et la., 2023)

Perspectives
The perspectives are the development of the adipocytes
modules and the first test of liver pathology using theliver pancreas axis

References
Scheidecker et al., Biofabrication 2024, in press
Morisseau et al., Molecular omics, 2023

eleclerc @ iis.u-tokyo.ac.jp

Fig 1: Metabolic syndrome concept using organ on chip52

Cryopreservation of IPSCs-Derived
Liver Cells for Toxicological Studies.
Carla Meschini
Keywords: Cryopreservation, IPSCs,
Organoids, Liver tissue

Fundings:
DOT Chaire
UTC (1/2)
Région des Hauts deFrance (1/2)

Context and Objectives

MethodAmong all in vitro models for toxicologicalstudies, Induced Pluripotent Stem Cells (IPSCs) derived cells constitute an alternative to primarycell lines regarding biomass availability [1].
However, the culture of this cell type is timeconsuming and represent a significant financial
cost.

IPSCs cells are differentiated into
hepatocytes using carboxypeptidase M
positive cells (CPM+ cells) sorting.
Selected cells are seeded into PDMS
honeycombs to form organoids [2].

Hosted in Sakai-Nishikawa Lab

The aim of this collaboration between the SakaiNishikawa laboratory and the Biomécanique et
Bioingénierie laboratory (France, UTC) is toestablish cryopreservation protocols for hepaticorganoids, to provide readily usable biomass
facilitating a broad range of applications such as
high throughput drug screening or toxicologicalstudies.

+Fig 1 : Organoids formation using PDMS
honeycombs technology (Created with
BioRender.com)

Results
A

B

Microscopy photos of CPM+ cells inbrightfield (A) and fluorescence showing
albumin (red) and cytokeratin-7 (green) (B).

-

3D organoids 4 weeks cultures-

Hepatocytes/cholangiocytes markers-

Liver like hetereogeneous subpopulations-

Functional characterisations: Albumin, Bile,
CYP450 assays Fatty acids metabolism

Perspectives

References-

Reproduce the protocol in France[1] M. Hussein et.al., Cells. 2023-

Controlled-rate slow freezing assay[2] T. Utami et.al., Biotechnology andBioengineering 2023

Comparison fresh vs freezing
Functional and disease models

carla.meschini @ utc.fr

53

Investigation of Non-Alcoholic Fatty
Liver Disease by Organ-On-A-Chip.
Hanyuan Wang

Fundings:
JSPS grant-in-aid for scientificresearch (B) 22H03934;
JPJSCCA20190006.

Hosted in Sakai & Nishikawa Lab
Keywords: palmitic acid, hepatocyte likecells, organ-on-a-chip, fatty liver disease

Context and Objectives

MethodNon-alcoholic
Fatty
Liver
Disease(NAFLD), a complex disorder with a highworldwide prevalence, is one of main causeof critical liver diseases. The lack oftherapeutic solution of NAFLD leads to an
unmet need to develop an efficient in vitro
disease model to investigate its onset,
propagation and the effects of drugs.

HLCs were differentiated from humaninduced pluropotent stem cells[1]. Afterseeding in a microfluidic biochips [2] (Fig1) HLCs took 7 days to mature under
perfusion (Fig. 1). After maturation, thecells were exposed to 0.1 mM and 0.5
mM of palmitic acid (PA) for another 7days to induce NAFLD.

In our study, we tested the effect ofpalmitic acid, a dietary fatty acid, on
hepatocyte like cells (HLCs) coupled withorgan-on-a-chip technology. We plan tomake an advanced NAFLD model withhigher similarity to in vivo situations andbetter longevity, then apply it for
pathological research and drug testing.

Fig 1:Photo of biochip and perfusion set up

Results

0.5 mM PA reduced lipidic genes
expression and down regulated related
pathways as shown in Fig 3.

PA exposures modified cell morphology
and 0,5 mM PA increased more collagensynthesis as shown in Fig. 2

Fig.2 endpoint morphology & collagen staining

Fig.3 down regulated processes in 0.5 mM PA

Perspectives

References

1) longer maturation and longer exposure;[1] Danoy, M. et al. Biochemical Engineering
Journal. 2022

2) tri-culture model with stellate cells andendothelial cells;3) mixed fatty acids to indice NAFLD.

[2] Baudoin, R. et al. Biotechnology Progress.
2007

wang-hanyuan517@g.ecc.u-tokyo.ac.jp

54

Investigation of the Liver Endothelium
Inflammation During Steatosis.
Hanyuan Wang, F. Soncin, Y. Sakai, E. Leclerc
Hosted in Sakai & Nishikawa Lab/ SMMiLE

Fundings:
Internal Project 2023
JSPS 22H03934;
JPJSCCA20190006.

Keywords: Liver model, organ-on-a-chip,fatty liver disease

Context and Objectives

MethodIt is estimated that around 24% and 30%
of European and Asian adults develop
NAFLD, 10-30% of them will evolve to themost severe form of NAFLD, i.e. nonalcoholic steatohepatitis (NASH), among
which 10-15% will develop liver outcomes(fibrosis). Industries face bottleneck todevelop new therapies because of the lackof human relevant models.

LSECs1, HSCs2 and Hepatocytes-likecells3 were differentiated from humaninduced pluripotent stem cells (Fig. 1).
After making stocks, the cells were usedin organ on chip cocultures (Sakai lab). In
parallel, the cocultures will be tested
using vessel like biochip (SMMiLE
technology). To simulate the NAFLD, freefatty acids exposure were performed.

In this study, we wish to extend ourhepatocyte like cells (HLCs) monoculture toa more complex coculture including liver
sinusoidal endothelial cells (LSECs) andhepatic stellate cells (HSCs). LSECs, HSCs
and the liver endothelium are involved in
the propagation of the inflammation during
the progression of the NAFLD.

HLCs

HSCs

Fig 1: Typical morphologies of HLCs,
LSECs and HSCs

Results

The immunostainings revealed theformation of a large endothelial-likenetwork in FA treated conditions

Tri cultures was succeed andFA
exposures lead to intense fiber likestructures as shown in Fig. 2.
Before FA exposure

LSECs

Control

After 10 days of FA

TreatedFig.3 Staining in green of albumin(Hepatocytes) and red PECAM1 (LSECs)

Fig.2: Morphologies before and during FA
exposures

Perspectives

References

1) Tri culture larger characterization;[1] Danoy, D. et al., Differentiation. 2021

2) Drugs testing;[2] Ya, G. et al., Biotech. Bioeng. 2023

3) Vessel coculture and ANR application[3] Danoy, D. et al., Hepa. Res. 2023

wang-hanyuan517@g.ecc.u-tokyo.ac.jp

55Full-Metal 3D Micro Fractal Pipette for
Magnetically Driven Liquid Sample Handling.
Gilgueng Hwang
Hosted in Mita Lab / B. J. Kim Lab
Keywords: Bio/chemical sample handling,
bioanalysis, drug delivery, Microswimmer

Fundings:
Internal project 2023
Kakenhi C

MethodContext and Objectives

Development of full-metalliquid/solid sample handling

MFPs

for

Proposed approach

Design/fabrication of 3D
printed MFP by 2photon
polymerization

Microrobotic biosample handling by
3D printed polymer micro fractal pipette [1,2]Sputtering seedlayers (Cr/Ni)

Current limitations:- Polymer structure: mechanically fragile- Tethered actuation: μ-robotic biosample
handling currently limited to laboratory
Electroplating Ni layer andrelease of full metal MFP

Goal: Fabricate full metal micro fractal pipette(MFP)

Fabrication of full metal MFP

Results
We fabricated full metal MFPs by electroplating of nickel layer on the 3D printed MFPs.
They can be applied for magnetic propulsion to swim in fluidic environment.
MFP1

MFP2

0s
500μm

100μm

SEM images of full metal MFP

Perspectives

0.5 s

1.2 s

Magnetic propulsion and trajectory
control of full metal MFP

References

The proposed method could open a new
possibility to fabricate metallic 3D micro/nano
structures. They are promising towards the
fabricationofmagneticallypropelling
microswimmers. More metallization processes
will also be tried to compare with the current
process and further improve the process.

56[1] D. Decanini, et. al., AIP Rev. Sci. Instrum. 91,
086104, 2020
[2] D. Decanini et al., JNTE 2022

hwang @ iis.u-tokyo.ac.jp

Subcellular Imaging During Single
Cell Mechanical Characterization.
Bahram Ahmadian

Fundings:
ANR
Region HdF / I-Site

Hosted in SMMiL-E
Keywords: Single-cell analysis, biophysicalcharacterization, subcellular imaging

Context and Objectives

Method• The state of a cell being linked to its•

Microfluidic device for cell handling•

Silicon Nano Tweezers for mechanicalmeasurements•

Confocal microscopy for subcellularimagingmechanical properties• Intracellular components having distinct
effects on mechanical properties• Can intracellular component properties
be linked to biological properties?

Results•

3D confocal imaging of subcellular components during compression•

Measuring mechanical properties of cancer cells
simultaneously with 2D imaging during compression

Fig.2: Mechanical characterization during
intracellular visualization.

Fig.1: Subcellular element imaging atdifferent compression levels.

Perspectives

References

Obtaining mechanical properties
ofdifferent cancer cell lines to distinguishthem[1] D. Pekin, G. Perret, et al, IEEE
International Conf. on MEMS, 62-65, 2020.

Linking mechanical properties of cells with
their subcellular components
Modelling cells to predict their metastatic
potential from mechanical properties

57[2] M. C. Tarhan, N. Lafitte, et al,
Scientific Reports 6, 28001, 2016.

ahmadian.bahram @ smmil-e.com

CYTOMEMS:
Instrumentation for BiophysicalCytometry with Statistical Learning.
Dominique Collard
Hosted in

SMMiL-E (Lille)

Funding:
ANR project

Keywords: MEMS cytometry, biophysicalcell characterization, AI

MethodContext and Objectives
The objective of CYTOMEMS is todemonstrate the first smart MEMS
equipment performing high content
biophysical characterization of cells inflow for their classification by statisticallearning.

Cell characterization is carried out by a
BioMEMS device incorporating a
microchannel for the passage of cells
and equipped with fixed and mobile
electrodes enabling both electrical andmechanical measurements of these cells
in flux. The position of the mechanicalsensor is tuned in real time tocharacterize the cell under controlled
deformations knowing the cell size fromupstream electrical measurement.
After a phase of training on different celllines, cell identification is performed bystatistical classification analyzing acomprehensive set of biophysical(electrical and mechanical) parameters.

fig.1 : Graphical view of the main objectives of CYTOMEMS recapitulating the main hypothesis.

.

Perspectives
CYTOMEMS is a 3 years ANR projects 2022-2024 with the following 4 partners :collard @ iis.u-tokyo.ac.jp58

Developing the Interdisciplinary
Space for SMMiL-E Projects.
Jean-Claude Gerbedoen & Fabrice Soncin
Hosted in SMMIL-E ( Lille)

Funding:
Internal project 2023

Keywords: Microfabrication, cell culturing,molecular biology, cellular biology

Context and Objectives

Microfabrication

SMMiL-E projects being at the intersection of
biology, engineering and clinics require
dedicated facilities within the hospital campus.

-Lithography (direct writing, mask aligner)

Imaging-Deposition(sputtering,
parylene coater)-Etching
etching)-Field emission scanning electron
microscopy (with a cryo option)-Airyscan confocal microscopy(ReactiveIon

evaporator,
Etching,

wet-Characterization (probe station, profilometer, SEM)

-Inverted microscopy for BF, Fl, PC and
DIC imaging-Upright microscopy for brightfield imaging-Rapid prototyping (stereolithography
SLA,nanoscribe
with
two-photon
polymerization,
computed
numerical
control)

L2 cell culture room
View of microfabrication equipment in thecleanroom

Cell Biology-Cell culture hoods-Tri-gas incubators

Bio-room-Culture under perfusion system

Molecular Biology-Classic & real-time PCR systems-Dedicated inverted microscopes with BF,
PC, and Fl imaging-DNA/RNA & protein quantification andanalyses equipment-Bioprinter-Abs/Lum/Fluo/Alphascreen plate reader-Nucleic acids & protein gel
imaging systems-Cell electroporation systemgerbedoen.jean-claude @ smmil-e.com
fabrice.soncin @ inserm.fr

59Integrating Impedance Cytometry with
MEMS: 3D Silicon Electrode Fabrication.
Faruk Azam Shaik
Hosted in SMMiL-E (Lille)

Funding:
ANR

Keywords: Microfabrication, electrodes,
MEMS, impedance.

MethodContext and Objectives
We aim to develop 3D silicon electrodes toperform impedance cytometry on single
cells without compromising practical
integration
withsensors
measuring
complementary
properties,e.g.,mechanical properties.

We tested the performance andfeasibility of three different designs.

Results

The third device type, i.e., type-3, had
an additional insulating layer at thebackside below the measurement area

A trajectory-free measurement is obtainedby replacing the silicon backside under thesensing area with an insulating material.
Widening electrode gaps and proper
insulation improves signal quality andreduces parasitic effects

The first device type, i.e., type-1, was anall-silicon device.
The second device type, i.e., type-2,
included an insulating material on thesides of the electrodes.

A PDMS slab was placed on the
fabricated silicon device to complete
the channel.

Perspectives

References

The proposed process aims at creating
silicon-based electrodes for impedance
spectroscopy applications while providing
opportunities to integrate them with MEMS
actuators and sensors[1] Q. Rezard, F. Shaik et al., MicroTAS, 805806, 2020.
[2] Q. Rezard, F. Shaik et al., IEEE Int. Conf. on
MEMS, 494-497, 2021.

faruk.shaik @ univ-lille.fr

60

Cells pairing tunable BIOMEMS device
for Immunology signaling protocol.
Dana Simiuc, Faruk Azam Shaik

Funding:
SATT Nord

Hosted in SMMiL-E (Lille)
Keywords: single cell interaction, cell pairing,
immunological synapse

MethodContext and Objectives
Immunological synapse (IS) is essential forinvestigating
efficientimmunologic
treatments for cancer studies.
We aim to fabricate a MEMS device forsingle cell pairing of individual immune
cells and leukemic cells for this purpose.

A multilayer microfluidic platform withspecific geometries targeting highthroughput deterministic pairing for two
different cell sizes in a unidirectional flow
format.
Introducing an auxiliary flow alters theeffective channel height allowing efficient
small-cell trapping.
In short, we perform controlled highthroughput
single-cell
pairingforimmunological synapse study.

Results
T cells and leukaemia cells are trap in controlled manner, with high throughput.
IS dynamics is monitored for hours.
Cell pairing is established for monitoring Ca2+ signature of T-cells.

Perspectives
Fabrication of integrated device for single
cell pairing.
Characterization of patients sample.
Calcium signature study.

References[1] Shaik F. A., et al, Lab Chip, 2022, 22, 908.
[2] Shaik F. A., et al, MicroTAS, 2022, 765-766.
[3] Shaik F. A., et al, MicroTAS, 2019, 634-635.
Figure 1: Cell pairing and monitoring theiractivities [1].

simiuc.dana @ smmil-e.com
faruk.shaik @ univ-lille.fr

61

Vascular Barrier Models in Cancer
Fabrice Soncin

Fundings:
ANR, Ligue contre leCancer, Fondation ARC,
IRCL

Hosted in SMMIL-E (Lille)
Keywords: blood vessels, cancer,
inflammation, immunity, microfluidics

Context and Objectives

Methods

We design blood vessel on-chip devices to
study
the
molecular
mechanisms which regulate the vascularbarrier, endothelial cell activation, and how
they participate in vessel integrity,
angiogenesis, and extravasation of bloodborne immune cells.

Blood vessels-on-chip are made in
PDMS-glass devices designed andfabricated at SMMIL-E facilities. They areseeded with primary human endothelial
and perivascular cells from variousorgans. Biological validations are madeusing confocal microscopy, RT-qPCR andfunctional assays.

We also study the effects of anti-cancer
therapies used in patients on the functionsof this vascular barrier

Blood vessel-on-chip 3D reconstruction

Results
Alice Leroy (Univ. Lille Ph.D student, Y2) studies the effects of anti-cancer
drugs and radiotherapy on the vascular barrier and immune activation in
our blood vessels on-chip models.
Ibtihal Hezili (Univ. Lille Ph.D.
student, Y1) sets up a perfused
blood vessel on-chipangiogenesis model to study theeffects of anti-cancer drugs andtherapies on this process.

Perspectives

References

Assess the role of biological signals &environment components on blood vessel
functions, screen for active drugs on bloodvesselpermeability,
activation,andangiogenesis.

[1] Viruses. 2023 May 16;15(5):1177[2] Toxicology. 2023 Jun 15;492:153550

fabrice.soncin @ inserm.fr

62

Distinguishing Cancer Cells Basedon Their Biophysical Properties.
Cagatay Tarhan

Fundings:
ANR
Region HdF / I-Site

Hosted in SMMiL-E (Lille)
Keywords: Single-cell analysis, biophysicalcharacterization

Context and Objectives

MethodBiological processes related to cells are
influenced by changes in cell shape andstructural integrity.

Microfluidic device for cell handling

Biophysical properties can potentiallyreflect the state of cells’ health.
Can we use biophysical parameters as
metastatic biomarkers?

Silicon Nano Tweezers for biophysicalmeasurements
AI for distinguishing cells(i) SNT tips for capturing single cells,(ii) Actuators for manipulation & detection,(iii) Capacitors as displacement sensors.

Results
Integrating SNT with microfluidics allows single cell characterization. Only tips enter a
microfluidic channel to capture a cell (Fig. 1). A displacement sensor allows compression
assays during continuous sensing. AI algorithms distinguish cell lines.
Three different breast cancer cell lines were analyzed. The cell line with high metastatic
potential (SUM159PT) shows softer mechanical properties than the cell line with low
metastatic potential (MCF7), which was softer than non-malignant cell line (MCF10A).

Fig.1: Compression assay with SNTs.

Fig.2: Comparison of three different cell lines.

Perspectives

References

Obtaining biophysical signature of CTCs
distinguishaccordingtometastatic
potential[1] B. Ahmadian, et al, IEEE MEMS, 317-320,
2022.

Towards diagnostic products, drug testing
platforms,
diseasemonitoring
andtreatment prediction instruments

63[2] T. Baetens, et al, IEEE MEMS, 608611, 2017.
[3] G. Perret, et al, MicroTAS, 826-7, 2017.

cagatay.tarhan @ junia.com

2024

Journals 2023-2024

1. T. Osaki, T. Duenki, SYA. Chow, Y. Ikegami, R. Beaubois, T. Levi, N. Nakagawa-Tamagawa, Y. Hirano & Y.
Ikeuchi. Complex activity and short-term plasticity of human cerebral organoids reciprocally connected withaxons. Nat. Comm. 15, 2945 (2024).
2. Y. Ikegami, T. Duenki, I. Arakaki, R. Sakai, T. Osaki, S. Ashihara, T. Furushima, Y. Ikeuchi, A simple andinexpensive laser dissection of fasciculated axons from motor nerve organoids, Front. Bioeng. Biotechnol.
12:1259138. (2024).
3. Messelmani T, Le Goff A, Soncin F, Souguir Z, Merlier F, Maubon N, Legallais C, Leclerc E, Jellali R, Coculture
model of a liver sinusoidal endothelial cell barrier and HepG2/C3a spheroids-on-chip in an advanced fluidic
platform, Journal of Bioscience and Bioengineering, 137, 64-75, 2024
4. Scheidecker B, Poulain S, Sugimoto M, Kido T, Kawanishi T, Miyajima A, Kim SH, Arakawa H, Kato Y, Nishikawa
M, Danoy M, Sakai Y, Leclerc E, Dynamic, IPSC-derived hepatic tissue tri-culture system for the evaluation ofliver physiology in vitro, Biofabrication, 2024 in press
5. Zhiyong Zheng, S. Grall, SH. Kim, A. Chovin, N. Clement, and C. Demaille, Activationless Electron Transfer ofRedox-DNA in Electrochemical Nanogaps, J. Am. Chem. Soc. 2024, 146, 9, 6094–6103
6. R. Anufriev, Y. Wu, S. Volz, M. Nomura, Quasi-ballistic thermal transport in silicon carbide nanowires, Applied
Physics Letters 124, 022202 (2024).
7. B. Kim, F. Barbier-Chebbah, Y. Ogawara, L. Jalabert, R. Yanagisawa, R. Anufriev, and M. Nomura, Anisotropy
Reversal of Thermal Conductivity in Silicon Nanowire Networks Driven by Quasi-Ballistic Phonon Transport,
ACS Nano 2024, 18, 15, 10557–10565.
8. S Koike, R Yanagisawa, L Jalabert, R Anufriev, M Kurosawa, T Mori and M. Nomura, Planar-type SiGe
thermoelectric generator with double cavity structure, Applied Physics Letters 124 (12) (2024).
9. J. Ordonez-Miranda, R. Anufriev, M. Nomura, and S. Volz, Harnessing Thermal Waves for Heat Pumping, Phys
Rev. Appl., accepted.
10. S. Tachikawa, J. Ordonez-Miranda, L. Jalabert, Y. Wu, R. Anufriev, Y. Guo, B. Kim, H. Fujita, S. Volz, and M.
Nomura, Enhanced far-field thermal radiation through a polaritonic waveguide, Phys. Rev. Lett. 132, 186904(2024).
11. Morisseau L, Tokito F, Lucas M, Poulain S, Kim SH, Plaisance V, Pawlowski V, Legallais C, Jellali R, Sakai Y,
Abderrahmani A, Leclerc E. Transcriptomic profiling analysis of the effect of palmitic acid on 3D spheroids of βlike cells derived from induced pluripotent stem cells. Gene. 2024 Apr 10;917:148441. doi:
10.1016/j.gene.2024.148441.
12. J Cacheux, T Nakajima, D Alcaide, T Sano, K Doi, A Bancaud, Y T Matsunaga, Protocol for fabricating andcharacterizing microvessel-on-a-chip for human umbilical vein endothelial cells, STAR protocols 5 (2), 102950(2024).

64

2023
1. J. Ordonez-Miranda, Y. A. Kosevich, M. Nomura, S. Volz, Long-range, short-wavelength, and ultrafast heat
conduction driven by three plasmon modes supported by graphene, Phys. Rev. B 108, L161404 (2023).
2. X. Wu, X. Huang, L. Yang, Z. Zhang, Y. Guo, S. Volz, Q Han, M Nomura, Suppressed thermal transport inmathematically inspired 2D heterosystems, Carbon, 213, 118264, (2023).
3. X Xiang, S Patinet, S Volz, Y Zhou, Quasilocalized vibrational modes as efficient heat carriers in glasses,
International Journal of Heat and Mass Transfer, 210, 124150, (2023).
4. C. Xu, G. Bonfante, J. Park, V.Salles and B. Kim, Fabrication of an electrospun polycaprolactone substrate forcolorimetric bioassays. Biomed. Microdevices 25, 32 (2023).
5. I. Madrid, Z. Zheng, C. Gerbelot, A. Fujiwara, S. Li, S. Grall, K. Nishiguchi, S.-H. Kim, A. Chovin, C. Demaille,
N. Clement, Ballistic Brownian Motion of Nanoconfined DNA, ACS Nano 17, 17031 (2023).
6. S. Li, Y. Coffinier, C. Lagadec, F. Cleri, K. Nishiguchi, A. Fujiwara, S.-H. Kim and N. Clement, Single-Cell
Electrochemical Aptasensor Array, ACS Sensors (2023) https://doi.org/10.1021/acssensors.3c00570
7. S. Grall, S. Li, L. Jalabert, S.-H. Kim, A. Chovin, C. Demaille, and N. Clement, Electrochemical Shot noise of a
Redox Monolayer, Phys.Rev.Lett. 130, 218001 (2023)
8. K. Chennit, Y. Coffinier, S. Li, N. Clement, A. Anne, A. Chovin and C. Demaille, High-density single-antibody
electrochemical nanoarrays, Nano Research, 16, 5412 (2023)
9. M. Awadein, M. Sparey, S. Grall, F. Kienberger, N. Clement and G. Gramse, Nanoscale Electrochemical
Charge Transfer Kinetics investigated by Electrochemical Scanning Microwave Microscopy, Nanoscale Adv. 5,659 (2023)
10. J. Cacheux, J. Ordonez-Miranda, A. Bancaud, L. Jalabert, D. Alcaide, M. Nomura, Y. T. Matsunaga, Asymmetryof tensile vs. compressive elasticity and permeability contributes to the regulation of exchanges in collagengels, Sci. Adv. 9, eadf9775 (2023).
11. J. Ordonez-Miranda, L. Jalabert, Y. Wu, S. Volz, and M. Nomura, “Analytical integration of the heater andsensor 3ω signals of anisotropic bulk materials and thin films,” J. Appl. Phys., 133, 205104 (2023).
12. M Danoy, S Poulain, B Scheidecker, SH Kim, T Kido, A Miyajima, Y Sakai, E Leclerc, Transcriptomic study ofcarboxypeptidase M-positive human pluripotent stem cells-derived liver progenitor cells cultured in a
microfluidic biochip shows zonation-like patterns, Hepatology research, 2023; 53, 661,
doi.org/10.1111/hepr.13893
13. Messelmani T, Zarpellon Nascimento I, Leclerc E, Legallais C, Meziane A, Cesar W, Jellali R, Le Goff A, Flowrate variations in microfluidic circuits with free surfaces, Microfluidics and Nanofluidics, in press
14. Messelmani T, Le Goff A, Soncin F, Gilard F, Souguir Z, Maubon N, Gakière B, Legallais C, Leclerc E, Jellali R,
Investigation of the metabolomic crosstalk between liver sinusoidal endothelial cells and hepatocytes exposed
to paracetamol using organ-on-chip technology, Toxicology,15;492:15355, 2023
15. Madiedo-Podvrsan S, Sebillet L, Martinez T, Bacari S, Zhu F, Cattelin M, Leclerc E, Merlier F, Jellali R, Lacroix
G, Vayssade M. Development of a lung-liver in vitro coculture model for inhalation-like toxicity assessment.
Toxicol In Vitro, 92:105641, 2023
16. Morisseau L, Tokito F, Poulain S, Kim SH, Plaisance V, Pawlowski V, Legallais C, Jellali R, Sakai Y, Abderrahmani
A, Leclerc E, Generation of b-like cell subtypes from differentiated human induced pluripotent stem cells in 3D
spheroids, Molecular omics, in press
17. D. Alcaide, J. Cacheux, A. Bancaud, R. Muramatsu, Y. T. Matsunaga "Solute transport in the brain tissue: what
are the key biophysical parameters tying in vivo and in vitro studies together?" Biomaterials Science (2023)
doi.org/10.1039/D3BM00027C
18. Z. Zheng, S.-H. Kim, A. Chovin, N.Clement and C. Demaille, Electrochemical response of surface-attached
redox DNA governed by low activation energy electron transfer kinetics Chemical Science 14, 3652 (2023)
19. J. Ordonez-Miranda, Y. A. Kosevich, B. J. Lee, M. Nomura and S. Volz, Plasmon Thermal Conductance andThermal Conductivity of Metallic Nanofilms, Phys. Rev. Appl. 19, 044046 (2023).

65

20. J. Ordonez-Miranda, M. Coral, M. Nomura and S. Volz, Resonant thermal transport driven by surface
phonon-polaritons in a cylindrical cavity, Int. J. Thermophys. 44, 73 (2023).
21. R. Gauthier, N. Attik, C. Chevalier, V. Salles, B. Grosgogeat, K. Gritsch and A.-M. Trunfio-Sfarghiu, 3DElectrospun Polycaprolactone Scaffolds to Assess Human Periodontal Ligament Cells MechanobiologicalBehaviour, Biomimetics 8, 108 (2023).
22. R. Anufriev, D. Ohori, Y. Wu, R. Yanagisawa, L. Jalabert, S. Samukawa and M. Nomura, Impact ofnanopillars on phonon dispersion and thermal conductivity of silicon membranes, Nanoscale, 15, 2248–
2253 (2023).
23. X. Huang, Y. Guo, Y. Wu, S. Masubuchi, K. Watanabe, T. Taniguchi, Z. Zhang, S. Volz, T. Machida, and M.
Nomura, Observation of phonon Poiseuille flow in isotopically-purified graphite ribbons, Nat. Comm., 14(1), 2044, (2023).
24. X Xiang, S Patinet, S Volz, Y Zhou, Quasilocalized vibrational modes as efficient heat carriers in glasses,
International Journal of Heat and Mass Transfer 210, 124150, (2023).
25. K Ghorbani, P Mirchi, S Arabha, A Rajabpour, S Volz, Lattice thermal conductivity and elastic modulus of
XN4 (X= Be, Mg and Pt) 2D materials using machine learning interatomic potentials, Physical Chemistry
Chemical Physics, 25 (18), 12923, (2023).
26. Z Zhang, Y Guo, M Bescond, M Nomura, S Volz, J Chen, Assessing Phonon Coherence Using Spectroscopy,
Phys. Rev. B, 107 (15), 155426, (2023).
27. Y Cheng, Z Fan, T Zhang, M Nomura, S Volz, G Zhu, B Li, S Xiong, Magic angle in thermal conductivity oftwisted bilayer graphene, Materials Today Physics, 35, 101093, (2023),
28. I. Persson, H. Laval, S. Chambon, G. Bonfante, K. Hirakawa, G. Wantz, B. Watts, M. A. Marcus, X. Xu, L.
Ying, G. Lakhwani, M. R. Andersson, J. M. Cairney, N. P. Holmes, Sub-4 nm mapping of donor–acceptor
organic semiconductor nanoparticle composition, Nanoscale 15, 6126 (2023)
29. L. Bourdon, N. Attik, L. Belkessam, C. Chevalier, C. Bousige, A. Brioude, V. Salles, Direct-Writing
Electrospun Functionalized Scaffolds for Periodontal Regeneration: In Vitro Studies, J. Funct. Biomater. 14,263 (2023).
30. N. Garnier, F. Sane, L. Massara, F.Soncin, P. Gosset, D. Hober, S.Szunerits, I. Engelmann. Genes Involved inmiRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection. Viruses. 2023 May 16;15(5):1177. doi:
10.3390/v15051177.

66

Conferences 2023-2024
2024
1. S. Volz, Guided Polaritons Thermal Radiation, MRS Spring Meeting 2024, Seattle, April 2024.
2. Maelie Coral, Saeko Tachikawa, Jose Ordonez-Miranda, Laurent Jalabert, Roman
Anufriev, Yannick De Wilde, Masahiro Nomura, Sebastian Volz, Far-field Surface Phonon
Polaritons-based Thermal Diodicity, PIERS 2024, Chengdu, April 2024.
3. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, 2D Far-Field
Thermal Radiation Driven by Surface Polaritons, PIERS 2024, Chengdu, April 2024.
4. Jose Ordonez-Miranda, Yuriy Kosevich, Masahiro Nomura, and Sebastian Volz, Long-range,
Short-wavelength, and Ultrafast Heat Conduction Driven by Three Plasmon Modes Supported byGraphene, MRS Spring Meeting 2024, Seattle, April 2024.
5. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, 2D Far-Field
Thermal Radiation Driven by Surface Polaritons, 8th Phonon Engineering Workshop, Miyako,
May 2024.
6. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, Quantum of
Far-Field Thermal Radiation between Subwavelength Films, Nanoscale and Microscale Heat
Transfer VIII, Girona, June 2024.
7. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, Net Heat
Current at Zero Mean Temperature Gradient, The 3rd Asian Conference on Thermal Sciences,
Shanghai, June 2024.
8. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, Quantum of
Far-Field Thermal Radiation between Subwavelength Films, Nanorad, Sapporo, July 2024.
9. Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, Harnessing
Thermal Waves for Heat Pumping, ICPPP, Coimbra, July 2024.
10.Jose Ordonez-Miranda, Roman Anufriev, Masahiro Nomura, and Sebastian Volz, 2D Far-Field
Thermal Radiation Driven by Surface Polaritons, IRMC, Cancun, August 2024.

2023
1. D. Decanini, A. Harouri, A. Mizushima, B. J. Kim, Y. Mita, G. Hwang, IEEE MEMS 2023, Munchen,
Germany, January 2023
2. Q. Rezard, F. A. Shaik, J.-C. Gerbedoen, F. Cleri, D. Collard, C. Lagadec and M. C. Tarhan,"Silicon compatible process to integrate impedance cytometry with mechanicalcharacterterization", 36th IEEE Int. Conf. on Micro Electro Mechanical Systems (MEMS'23), pp.
475-478, (2023).
3. S. Volz, Heat Transport driven by Surface Phonon-Polaritons, Thermal Polaritonics Workshop,
Tokyo, invited, 2023.
4. S. Volz, SuperPlanckian Far-Field Phonon-Polaritons, APS Spring 2023, San Francisco, invited,2023.
5. S. Volz, Temporal Coherence in Heat Conduction, 3rd SMST, Shenzhen, 1-3 June 2023, keynote.
6. S. Volz, Surface Polaritons Heat Carriers, IWCIC 2023, Tokyo, June 2023, invited.
7. S. Volz, Guided Resonant Modes yield SuperPlanckian Radiation, PIERS,
Invited.

Praga, July 2023,

8. S. Volz, THERMAL POLARITONICS A FOURTH HEAT TRANSFER MODE?, IHTC, Cape Town,
August 2023, keynote.

67Conferences 2023-2024
9. Morisseau
L,
Rodriguez-Fernandez
J,
Gallego-Ferrer
G,
TolosaL,
Legallais C, Jellali R, Sakai Y, Salmeron-Sanchez M, Leclerc E, Modelling Non-Alcoholic Fatty
Liver Disease by culturing HepG2C3A cells using a microfluidic biochip combined with abiomimetic hydrogel, yESAO Exchange Program Award 2023, ESAO 2023, Bergamo, Italy
10.Wang H, Danoy M, Tia U, Ya G, Choi H, Arakawa H, Kato Y, Nishikawa M, Sakai Y, Leclerc
E,Investigation of the effect of palmitic acid on hepatocyte-like-cells derived from humaninduced pluripotent stem cells using liver on chip, JSAO 2023, Tokyo , Japan
11.Morisseau L, Pawlowski V, Plaisance V, Legallais C, Sakai Y, Abderrahmani A, Jellali R, Leclerc E,
Investigation of oleic acid, palmitic acid and their mixture on the development of hepatic
steatosis using liver-on-chip technology, ESAO 2023, Bergamo, Italy
12.J. Cheslet, R. Beaubois, U. Rançon, L. Bailly, M. Bernet, T. Kohno, B. Yvert, T. Levi, FPGA
implementation of a Spiking Neural Network for Real-Time Action Potential and Burst Detection,
IEEE BioCAS 2023, Toronto, Canada
13.F Soncin. Vaisseaux sanguins-sur-puce pour de nouveaux modèles 3D de barrière vasculaire.
15èmes Journées du Cancéropôle Nord-Ouest, Deauville
14.F Soncin Blood vessels-on-chip models of the vascular barrier. Webinar series Société Française
d'Angiogenèse, online June 1st, 2023

Book Chapters 2023-2024
Gines, G., Genot, A.J., Rondelez, Y. (2023). Parallel Computations with DNA-Encoded
Chemical Reaction Networks. In: Jonoska, N., Winfree, E. (eds) Visions of DNA
Nanotechnology at 40 for the Next 40 . Natural Computing Series. Springer,
Singapore. https://doi.org/10.1007/978-981-19-9891-1_19
L Morisseau, T Messelmani, A Essaouiba, Y Sakai, C Legallais, E Leclerc, R Jellali,
Microfluidic and organ on chip based technologies for diabetes therapy and research,
Nanotechnology for diabetes management, Royal Society of Chemistry, 2023, Edited
by, Amar Abderrahmani, Sabine Szunerits, Rabah Boukerroub, Abdelfattah El
Ouaamari, Paperback ISBN: 9781839164705

68

Acknowledgements
LIMMS would like to thank The University of Tokyo and the CNRS for theircontinuous support.
We gratefully acknowledge the Japan Society for the Promotion of Science,
JSPS, for its continuous support to LIMMS via its JSPS-fellowship programsand via Core-to-Core Program (A. Advanced Research Networks). We finally
thank the French (ANR), European (H2020) and Japanese (JST, JSPS, NEDO)
funding agencies for their competitive funding.

Notes69