別紙5 (論文博士)
Date of subn11Sslon

令和元午 06児

06日

Depa11menl

Electlical and Electronic11〕fom〕ation En meelin
ConねCtApplicanl's name

氏名facu】1Y

LeeYOU・Na

紹介教仁

PTof. Kazuaki sawada

Abstract

論文内容の要旨(博士)Tltle ofTI]esis

博士学位論文名

Image sensor techn010gy for visualizing n〕ultl・neurotransmitters(APPI'O×.80O W01'ds)(要旨 1,200字程度)
Recenay the scientiHc studies ofthe nel'vous system have incl'eased substantiaⅡy with advances in analyticaleq山Pment.1hose are wildly conthbuted it possible to undel'stand ho、¥ biochelnical signals are tl'ansm北ted
thl'ough synapuc juncti011S by the l'elease and 11〕e feedback of ne山、otl'ansm轍ers.1heil' studies and thedevelopment of medicines l'equire effective analysis eq山Pment to quantify biochemical activities in ne山'onal

Comln山]ications and sevel'al analy[ical techniques have been developed. However, most of the analyticaltecl】niques focus on the detection of a single neul'otl'ansmitter, evel] dlough neurons comm山licate in aConlplex interaction of neul'otl'ansmittel'S.1t led to the development of lsfEl an'ay based bio、image senso】・
Which is portable and customizable as weⅡ as implantable fo】'10ng・tenl】 1'ecording.＼NI]en comparing to ne山・alProbe arrays 、vhlch are successfU11y applied to electl'ical signal recording ln the bl'ain, bioch引nical rec01・dino

may be more complicated due to the diversity of ne山'otl'anslnitters, but it is very encouraging by their
Similality between t1祀 PI'obe and lsFET an'ays.

In thiS 廿lesis,、ve wi11intl'oduce a bio‑image sensor whicl】 is lsFElbased enzyme sensor an'ay with integrated
With readout in m'del' to monitm' spatiotemporal activities of val'ious neul'otl'ansmitters in the same time.
ThiS 小esis consists ofthree main pa11S:

1、＼ve i11Vented new enzyme・immobilization technique using conventional photolitho01'aphy. Befbre
developina a bio‑image sensor used for spatiotemporal monit01'ing of m01'e t11an two neul'otl'anslni廿ers, wePI'oposed an enzyme・immobilization teclmique 小at is tl〕e integration of an imaging device teclm010gy andISFEl based enzyme sensor. using t11is teclmique, we can not 01]1y simply select t11e kinds ofProton・conS山ning or‑generating enzymes acc01'ding to the neul'otransmiせel's wishing to analyze, but also

immobilize them in a planned shape on a pH image sensor by conventi01]al photolithography tecl〕n010oy, The
Prototype applying the suggested teC11nique was fabl'icated and tested to hnage the concentl'ation gl'adient of
ATp and H". During the measurements, we became i】〕terested in H' di仟Usion via liquid、 since the degraded
Alp also by enzymatic reaction generates H' and the di仟Used H、 were ab】e to contl'ibute to signalinterrupting
among neighboring pixels.＼Nhen designing and placement ofenzyme・immobilized pixels、 the crosstalk by theH、' di仟Usion should be considered to imp】'ove the target discriminability ofa bio、image sensor

2. we tl】en applied this technique to fabl'icate AIP, AC11 and H'、image sensor as a f山lher development ofour
Previous l'eseal'ch.1his bio・image S引Isor contained a pattemed enzyme、immobilized membl'ane, as smaⅡ as aPixel size, to enhance spatial resolution. Moreovel', several attempts, such as ne、v pattem placements, ban'ierIayers and micl'ohole arrays, were attempted t0 1'educe the H' di仟Usion via liquid.1he fabl・icated bio、image
Sensors wel'e demonstl'ated to confinl】 their multi、detection and discrimination abilities to visualize theConcentl'ation C11anges ofAlp and Ach in l'eal、time 2D ilnages

3. AdditionaⅡy, we modi行ed the circuit desion ofthe pH・image sensor to h11Prove spatiotempora11・esolution inOrdel' to investigate tl】e ne山'al netw01'king in detail. TI】e pH image sensor was developed towal・d lal・ge、scale,high・denS北y and fast 行ame 】'ate lmaging.1he pH image sensor was fab↑icated by a modi6ed cMos processtecl]n010gy. A sma11 Pixel pitch was achieved by utilizing a shlunken in‑pixel cil'cuit and an ef打Cienuy
a"'anged l'eadout circuit architecture. M01'eover, t11e frame rate was able to accelel'ate by ope】'ating steps ofmeasunng and read out in pal'aⅡel、 we dem01】stl'ated the imaging capability with our evaluation method for

PI'actical high‑spatial resolution in bi010gical environments and compared the exP引'imenta11'esult with 111e
Simulation result to fig山'e out the reason tl]en