IWIT

Hiro

ABSTRACT An implnewly develoand a perfusiestablished a could observemicroscopy (Tmicrochannel KEYWORDImplantable d

INTRODUC

The obserchallenges incell[2], but thtissues. To adfunction using

DEVICE PR

The devicmm in diameheight) is seachemicals froTetra-PEG getreatment. Thchemical bon

Figure 1. Brdevice moun

IMPLANTH DRUG

oaki Takeha

2Resea3Center for

T antable micro

oped for the inion membrandevice manu

e neural cellsTPLSM). Furls in the devic

S device, neural

CTION rvation of neun neurosciencehere is still rooddress these pg a PDMS/Tet

RINCIPLE ce, which waseter and 500 μled with the n

om the microcel was sterilizhe microchands.

rain interfacented on a mou

a

b

NTABLE MG PERFU

ara1,2, Akira

1School ofarch Fellow ofDisease Biolo

ofluidic devicen vivo analysine made of Tufacturing pros in a living mrthermore, we e.

cell, two-pho

ural cells in the[1]. We repoom for improvproblems, we tra-PEG hydro

s designed to μm in thicknesnewly designechannels into zed by filtratnels were sea

device with ause skull. (b) S

MICROFUSION FU

MEMNagaoka2,3,

and Taf Engineering

of the Japan Soogy and Integr

e with a functs of neural ce

Tetra-PEG gelocedure fully mouse brain i

demonstrated

ton laser scan

e intact brain orted an implavement in the

have developogel hybrid m

be implantablss (Figure 1).

ed high-strengbrain tissues. tion and PDMaled with Tet

a permeable hySchematic of a

FLUIDIC UNCTIONMBRANE, Jun Nogucakanori Ichig, The Universociety for the

grative Medicin

tion of drug pells. The devicl, which is a

y compatible win good physid the local del

nning microsco

of a living anantable microcontrollability

ped an implanmicrochannel.

le into a certaThe bottom o

gth biocompatiThe fabricati

MS with micrtra-PEG gel

hydrogel memba microchanne

INTERFN THROE chi3, Takanoiki1 sity of Tokyo, JPromotion of ne, The Unive

perfusion throce has a hybri

high-strengthwith the steriiological condlivery of mod

opy, brain, tet

nimal using Tofluidic devicy of the dose ntable microf

ain part of theof the microcible hydrogel ion procedurerochannel struby the bindin

brane. (a) Schel in the devic

FACE DEVUGH HY

ri Akagi1, H

Japan f Science, Japaersity of Tokyo

ough a hydrogid structure ofh biocompatibilization procdition by two-del chemicals i

tra-PEG hydro

PLSM is one e for the in vamount and d

fluidic device

e skull to closhannels (100 called Tetra-Pof the device

uctures was sng of Tetra-P

hematic of the e.

VICES YDROGE

Haruo Kasai

an o, Japan

gel membranef PDMS microble hydrogel.

cess. Consequ-photon laserinto brain tiss

ogel

of the most svivo analysis delivered spac

with a drug

se a drilled hoμm width an

PEG gel[3] toe is shown in sterilized by

PEG gel to P

microfluidic i

L

i3

e has been ochannels . We also uently, we r scanning sues using

significant of neural

ce in brain perfusion

ole, is 2.7 d 200 μm

o transport Figure 2. autoclave

PDMS via

interface

16th International Conference on Miniaturized Systems for Chemistry and Life Sciences

October 28 - November 1, 2012, Okinawa, Japan978-0-9798064-5-2/μTAS 2012/$20©12CBMS-0001 189

EXPERIMEPrior to th

numerical simsimulation resapplicable to

Figure 3. (cross sectiof fluorescExperimenconcentratdeviations.

Figure 2. (a)Photograph hydrogel. Th

a

a

NT he implantati

mulation of thsults showed the well-contr

(a) Schematic on of the micr

cein after the dntally measurtion (CFEM; so.

a) Fabricationof the microf

he device is 2.

on experimenhe flow and di

excellent agrerolled delivery

illustration ofrochannel aftedelivery of 5 μred fluorescenolid lines) at

n process of thfluidic interfac7 mm in diam

d

nts, transient iffusion in theeement, as shoy of chemicals

of Tetra-PEG ger the deliveryμM fluoresceinnce intensity various depth

he device. PDce device. The

meter and 500 μ

b

diffusion expe device usingown in Figures or drugs into

gel/PDMS hyby of 5 μM fluon for 10 min c(IExp.; symbo

hs (50 μm, 1

DMS with mice device is im μm in thickne

periments werg the CFD-ACe 3. Thus, theo the mouse b

brid microchaorescein for 10alculated by t

ols) and comp00 μm, 200 μ

crochannels wmersed in wa

ess.

b

re performed.CE+ software.e device develrain.

annels. (b) Flu0 min. (c) Conthe finite-elemputationally μm). Error ba

was sealed witter to avoid th

c

. We also con

. The experimloped was pro

uorescence imncentration disment method (F

calculated fluars show the

th Tetra-PEG he deformatio

nducted a mental and oved to be

mages of a stribution FEM). (d) uorescein standard

gel. (b) on of the

190

Then, in vwas observeddevice was ssolutions wersubstance in b

CONCLUSIO

We havemembrane ftissues of livin vivo analy

ACKNOWL

This resea REFERENC[1] Helmche[2] Takehara

scanning[3] Sakai, T.

from tetr CONTACT Hiroaki Takeh

Figure 4bars: (a)

Figure 5. (ainject solutifluorescent

a

b

vivo experimed by TPLSM, asufficiently stre injected intbrain tissues w

ON e presented tfor deliveringving animalsysis in the fie

LEDGEMENTarch was supp

CES en, F., et al., Da, H., et al., g microscopy,., et al., Desigrahedron-like

hara, tel: +81-3

4. (a) Bright ) 500 μm and

a) A living moions into the substance in b

a

ents were demand high-resoterilized and to the microchwas measured

the usefulnesg chemicals . Implantableeld of neuros

TS orted by Gran

Deep tissue twMicrofluidic , Proceedings gn and fabricat

macromonom

3-5841-1180; h

image of the (b) 100 μm.

ouse immobilimicrochannelbrain tissues a

monstrated as folution (<1 μm

the pulsatile hannels of theby TPLSM (F

ss of an impin a control

e microfluidiscience and f

nt-in-Aid for J

wo-photon micinterface devof MicroTAStion of a high-

mers. Macrom

h-takehara@bio

brain surface

ized with the ls. (b) Deviceat depths of 25

follows. The bm) microscopy

motion was e device, and Figure 5).

plantable milled manneric device tec

for the discov

JSPS Fellows

croscopy, Natuvices for in vi 2010 confere-strength hydr

molecules, vol.

onano.t.u-toky

e under the d

headgear. Tefe in the headg5 μm and 50 μ

c

b

brain of a liviy images of ne

successfully the diffusive

crofluidic deand for obs

chnology is every of drugs

(22-8063).

ure Methods vivo analysis oence, pp. 2111rogel with ide 41, pp. 5379-

yo.ac.jp

device. (b) Two

flon tubes wergear. Scale baμm. Error bar

ng mouse impeural cells wersuppressed (Ftransfer of th

evice with a erving fine

expected to bs for treating

vol. 2, pp. 932of neural cell-2113 (2010).

eally homogen-5384 (2008).

o-photon imag

re connected tar: 2 mm. (c)rs show the sta

planted with tre obtained be(Figure 4). Flhe delivered fl

a permeable structures of

be a powerfug brain diseas

2-940 (2005). ls using 2-pho. neous network

age of neural

to the device ) Diffusive traandard deviat

the device ecause the luorescent luorescent

hydrogel f cells in

ul tool for ses.

oton laser

k structure

cells. Scale

tubes to ansfer of tions.

191