Our target
Chapter 6. Neurotransmitter detection using the MEMS interferometer with
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Chapter 6. Neurotransmitter detection using the
92
i m pl ement ed , t he num ber of pat i ent s wi t h t hese di seases can be r educed . For t he det ect i on of t hese neur ot r ansmi t t er s , MEMS sur f ace - st r ess sensor s based on r ecept or- bi ndi ng pr otei ns and FET bi osensor s based on enzym ati c r eact i ons have been devel oped and t hei r sensi t i vi t y has been i m pr oved. I n t he f orm er, by f ocusi ng on t he abi l it y of recept or - bi ndi ng pr otei ns t o change t heir own st r uct ure dependi ng on neur ot r ansm i tt er ' s concent rat i on, and det ect i ng sur f ace st r ess change because of t he st r uct ur al change, acet yl chol i ne ( ACh) , whi ch i s a known neur ot r ansm it t er, was det ect ed at a concent r at i on of 10 nM [ 97] . I n t he l at t er, by det ect i ng t he change i n charge densi t y i n hy dr ogen i on caused by enzym e r eact i on, ACh at a concent r at i on of 0.5 –1000 uM was det ect ed [ 98] . However, t he r ecept or-bi ndi ng pr ot ei ns used i n t he pr evi ous r eport have sever al pr obl em s: t he r eagent s ar e expensi ve, det ectabl e sm all m ol ecul es ar e l i mi t ed, and t hey l ack ver sat il i t y;
t hus , t her e ar e f ew e xam pl es of det ect i ng neur ot r ansm it t er s using sur f ace - st r ess sensor s. The l at t er m et hod usi ng enzyme al so has sever al pr obl em s: l ack of st abi l it y, expensi ve , and r equi r e m uch t ime t o pr oduce, t hus not bei ng sui t abl e f or l ong - t er m st or age [ 99] . Ther ef or e, MI P s have becom e pop ul ar as al t er nat i ves t o t hese m ol ecul ar adsor pt i on l ayers . Thi s t echni que ut il i zes t he speci f i c bi ndi ng of t arget m ol ecul es to t he t em pl at e by f orm i ng a tem pl at e of t he t arget m ol ecule i nsi de t he MI P. The m ol ecul ar i m pri nt i ng m et hod has sever al feat ur es: it can be devel oped f or any t em pl at e, i t i s st abl e in var i ous condi t i ons ( pH, t em per at ur e, i oni c st rengt h, sol vent s) , cost - eff ect i ve synt hesi s, and l ong t erm st or age wi t hout l oss i n per f or mance ( se ver al m ont hs t o year s) [ 100] . However, when f or m i ng m acr om olecul ar tem pl at es, t he pr obl em of var yi ng bi ndi ng aff i nit y i s encount er ed because of i t s st r uct ural change. Ther ef or e , when det ect i ng m acr om ol ecul es usi ng MI Ps , t he f or mat i on of epi t ope t em pl at es, whi ch i s t he sm al l est si t e wher e t he ant i body m ol ecul e r ecogni zes t he ant i gen m ol ecul e , has been pr oposed [ 101] . However, s i nce pr odu ci ng t he epi t opes i s expensi ve , t he ant i body - based m et hod i s a pr act i cal sol ut i on of det ecti ng m acr om ol ecul es i n sur f ace -st r ess sensors. As an exam pl e of MI P devi ces, by f or m i ng an MI P on t he gat e - elect r ode of an FET and by det ect i ng t h e change charge densi ty caused by t he t arget adsor pt i on t o t he t em pl at es, DA, whi c h i s known as a neur ot r ansm it t er, has been successf ul l y det ect ed at a concent r at i on of 96 nM [ 99] . Ther ef or e, i f t hi s MI P can be f or m ed on t he MEMS i nt er f er om et er, l ow- m ol ecular- wei ght neur ot r ansm i t t er s t hat have been di ff i cul t t o det ect usi ng convent i onal sur f ace - str ess sensor s can be det ect ed .
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6 . 3 I n t r o d u c t i o n o f m o l e c u l a r l y i m p r i n t e d p o l y m e r s
Tabl e 1 shows t ypi cal m onom er s and f orm at i on t echni ques f or MI P s and t hei r f eat ur es. Oxi dat i ve pol ym er i zat i on [ 102] –[ 104] , i n whi ch MI P s ar e f or m ed by suppl yi ng oxygen t o t he r e act i on sol ut i on, can be f or m ed on an y subst r at es, but f or m i ng t hem wi t h uni f or m f i lm t hi ckness and densi t y i s di ff i cul t . Fur t her m or e, t he def or m abl e m embr ane easi l y st i cks to t he Si subst r at e when t he bubbl es gener at ed dur i ng oxygen suppl y t ouch t he f r eest andi ng st r uct ur e, r esul t i ng in devi ce f ai l ur e. I n addi t i on, MI P s usi ng UV i r r adi ati on ar e f or m ed by dr op - cast i ng a m i xt ur e of t arget m ol ecul es and cr oss - li nker s i n a l ow - m ol ecul ar- wei ght sol vent , f ol l owed by t he cr oss- l i nki ng of t he sol vent usi ng UV i r r adi at i on [ 105] , [ 106] . I n t hi s t echni que, t he MI P s can be f or m ed onl y i n t he i r r adi at ed area by i m m er si on i n a st r i ppi ng sol ut i on af t er exposur e wi t h a shadow m ask dur i n g UV i r r adi at i on.
However, because of t he use of t he aci di c sol ut i on i n t he pr ocess of r em ovi ng t he i m pr i nt ed m ol ecul es, avai l abl e m at eri al s in t he sensor ar e l i m it ed. I n cont r ast , el ect r ochemi cal pol ym er i zati on [ 107] –[110] , i n whi ch MI Ps ar e f orm ed by r epeat ed pot ent ial sweepi ng i n t he r eact i on sol ut i on, i s charact eri zed by t he easy cont r ol of f i l m t hi ckness and t he f or m at i on of hi gh - densi t y pol y m er i zed f i lm s ; it can be used onl y on conduct i ve m at er ial s. I n addi t i on, when D A i s used as t he i m pr i nti ng m ol ecul e, t he DA i s r em oved by i m m er si on i n et hanol , and t em pl at es can be easi l y f or m ed [ 111] . When f or mi ng MI P s on t he MEMS i nt er f er omet er, a hi gh - densi t y MI P shoul d be f or m ed t o uni f or m l y appl y sur f ace st r ess t o t he def or m a bl e m em br ane. Fur t her m or e, sel ect i ng hi ghl y r ef l ect i ve m at er i al s f or t he m i r r or sur f ace of t he i nt er f er om et er im pr oves t he wavel engt h s el ect i vit y and t he out put r esponse when a sm all defl ect i on of t he def or m abl e mem br ane occur s [ 93] . Ther ef or e, we sel ect ed pol ypyr r ol e (PPy) f or m ed usi ng el ect r ochem i cal pol ym er i zat i on as t he MI P l ayer t o sati sf y t hese condi t i ons .
94
Tabl e 6.1. Com par i son of MI P - based co m m on m onom er s and pol ym er i zat i on pr ocedur e, and t hei r pr oper t i es.
M o n o m e r P o l y m e r i z a t i o n
P r o c e d u r e A d v a n t a g e D i s a d v a n t a g e
D o p a m i n e O x i d a t i o n C a n b e f o r m e d o n a n y
s u b s t r a t e U n a b l e t o f o r m u n i f o r m f i l m t h i c k n e s s a n d d e n s i t y
B o r o n i c
a c i d U V E a s y p a t t e r n i n g U V i m p a i r s t h e f l e x i b i l i t y
o f t h e m o v a b l e m e m b r a n e
P y r r o l e E l e c t r o c h e m i c a l
C a n b e f o r m e d h i g h -d e n s i t y p o l y m e r i z e -d f i l m w i t h e a s y c o n t r o l o f f i l m t h i c k n e s s
C a n b e f o r m e d o n l y o n c o n d u c t i v e m a t e r i a l s
6 . 4 F a b r i c a t i o n p r o c e d u r e
Fi g. 6.1 shows t he f abr i cat i on pr ocedur e of t he MEMS i nt er f er om et er wi t h an MI P f i l m . Thi s MEMS i nt er f er om et er f or m ed a cavi t y - seal ed st r uct ur e t hr ough t he dr y t r ansf er of nanosheet s f abr i cat ed f r om conduct i ve m at er ial s ( e.g. Au) and par yl ene def or m abl e m em br ane t o t he cavi t y - f orm ed chi p. T he det ai l s of t he f abr i cat i on pr ocedure ar e as f ol l ows:
( a) Cavi t i es wer e f or m ed usi ng deep RI E on the Si subst r at e. Si nce t he cavit y dept h f or m ed i n t his pr ocess corr espond ed t o t he ai r- gap lengt h of t he i nt er f er om et er, t he cavi t y dept h was sel ect ed such t hat t he def or m abl e m em br ane di d not adher e t o t he bot t om sur f ace t hr ough l i qui d pr essur e.
( b) Af t er t he adhesi on on Si was i m pr oved thr ough si l ane coupling t r eatm ent , par yl ene C was deposi t ed usi ng vapour deposi t i on. Thi s par yl ene f unct i oned as a bi nder when par yl ene f uncti on i ng as t he def orm abl e mem br ane was t r ansf er r ed t o t he chip wi t h cavi t i es.
( c) Par yl ene C was dep osi t ed on t he Si subst r at e af t er spi n coat i ng wi t h a sur f act ant (Mi cr o - 90, Pr oduct s Cor p.) , and t hen Au was depos i t ed usi ng a shadow m ask t o f or m t he el ect r ode shape.
( d) Af t er t he car r i er t ape was at t ached t o t he waf er, t he Au/ par yl ene C f i l m was r el eased f r om t he Si subst r at e by i mm er sing i t i n DI W and r eact i ng i t wi t h a sur f act ant .
( e) The r el eased def orm abl e m em br ane was t ransf er r ed t o t he chi p wi t h cavi t i es on pol yt et r af l uor oet hyl ene ( PTFE) , f ol l owed by t he appl i cat ion of heat at 160 °C f or 1 h.
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( f ) The i nt er f er om et er was i m m er sed i n a m i xed sol ut i on consist i ng of KCl buff er : Pyr r ol e: DA = 100: 10: 20 m M. By per for m i ng a pot enti al sweep f or t hr ee cycl es i n a r ange of -1–1 V and a speed of 0.04 V/ s vi a a pot ent iost at , PPy of MI P f i lm s on Au wer e sel ect i vel y f orm ed.
( g) The dopam i ne im pr int ed i nsi de t he polypyr r ol e l ayer was r em oved by i m m er si on i n et hanol and t em pl at es are f orm ed i n t he f i lm .
( h) The car r i er t ape and PTFE wer e r em oved f r om t he chi p.
Fi gur e 6.1: Fabr i cat i on pr ocedur e of MEMS i nt er f er om et er wi t h m ol ecul ar i m pr i nt ed pol ym er f ilm
Au Shadow mask
Micro-90 Si substrate
Carrier
tape DIW
PTFE
KCl buffer
f. Formation of polypyrrole membrane by electrochemical polymerization.
Polypyrrole
Counter Reference Working
Potentiostat
A V
Ethanol
a. Patterning cavity and treating with silane coupling agent.
b. Deposition of parylene C
c. Sputtering Au after deposition of parylene C with surfactant.
d. Releasing from bottom wafer by immersing in DIW.
e. Dry transfer onto a chip with cavity pattern, and annealing for improvement of adhesion between parylene layers
g. Formation of DA templates by immersing in ethanol.
h. Removal of carrier tape and PTFE
96 6 . 5 F a b r i c a t i o n r e s u l t s
Fi g. 6.2 shows an o p t i cal mi cr oscope im age of t he f abr i cat ed i nt er f er om et er wi t h an MI P fi l m and t he r ef l ect i on spect r um obt ai ned when whi t e l i ght was i r r adi at ed t o t he i nt erf er om et er. The ar ea funct i on ed as t he def or m abl e m em br ane of t he i nt er f er om et er was f or m ed t o be 50 µm i n di am et er ( Fi g. 6.2a) . Fi g . 6.2c shows t he r ef l ect i on spect r um when t he l i ght was i r r adi at ed at t he cent r e par t of t he i nt erf er om et er usi ng an opt i cal f i br e wi t h a di amet er of 200 µm and a 20 × obj ect i ve l ens. The obt ai ned r ef l ecti on spect r a ar e pl ot t ed on t he gr aphs wi t h t he opt i cal anal ysi s r esult s based on t he opt i cal anal ysi s m odel of t he i nt er f er om et er shown i n Fi g . 6.2b. Al l t he peaks of t he anal yt i cal wavef or ms wer e i n good agr eem ent wi t h t he measur ed val ues, i ndi cat i ng t hat t he i nt erf erom et er st r uct ur e whi ch was cl ose t o t he anal yti cal m odel was f or m ed; t he dom ai n st r uct ur e obser ved on t he f i l m was consi der ed t o be caused by t he no n - uni f or m st res s appl i ed t o t he def ormabl e m em brane because of t he l ocal depositi on of aggr egat es of Pyr r ol e, a m onom er of PPy, on Au. Thi s phenom enon coul d be sol ved by set ti ng a sl ower sweep r at e dur i ng el ect r ochem i cal pol ym er i zati on.
Fi gur e 6.2: ( a) Opt i cal m i cr oscope i m age and ( b) opt i cal anal ysi s m odel , and ( c) r ef l ecti on spect r a of devel oped Fabr y - Per ot i nt er f er om et er and anal ysi s cur ve.
The com posi t i on of t he PPy f i l m f or m ed by el ect r ochemi cal pol ym er i zati on was eval uat ed usi ng Raman spect r oscopy i n t he st at e of pr esence or absence of DA.
Fi g . 6.3 shows t he m easur ed Ram an spect r a. I n t he previ ous r esear ch [ 111] , peaks owi ng t o t he C=C bo nd i n PPy wer e r epor t ed t o appear at 1335, 1414, and 1590 cm- 1, and weak peaks at 1265 –1269 cm- 1 a nd 1479 –1495 cm- 1 o wi ng t o t he C- O bond i n DA . I n t he Ra m an spect r a obt ai ned i m m ediat el y aft er PPy f or m ati on, PPy -der i ved peaks ( 1334, 1416, 1590 cm- 1) and DA - der i ved peaks ( 1 267, 1486 cm- 1) appear ed, whi l e af t er r em oval of DA, onl y t hr ee PPy - der i ved peaks ( 13 35, 1414,
(a) (b) (c)
50 µm
Measured
area
Si substrate
Parylene C 210 nm Au 42 nm
PPy 80 nm
Air gap 5.45 µm
5000 550 600 650 700 750 800 0.2
0.4 0.6 0.8 1
Wavelength (nm)
Reflectance (a.u.)
Fitting curve
Experiment
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1590 cm- 1) appear ed. These r esul t s suggest ed t hat DA was rem oved and t he t em pl at es wer e f or m ed i n t he MI P f i lm .
(a) (b)
Fi gur e 6.3: Ram an sp ect r a i n m ol ecul ar impr i nt ed pol ym er ( a) af t er deposi t i on of PPy and ( b) af t er r emoval of DA.
6 . 6 A c q u i s i t i o n o f s e n s o r r e s p o n s e t o n e u r o t r a n s m i t t e r
Fi g. 6.4 shows a schem at i c di agr am of t he exper i m ent al set up t o m easur e t he r esponse of t he adso r pt i on of neur ot r ansm i t t er s. I n t hi s exper i m ent , t he sensor chi p wi t h D A t e m pl at es was i m m er sed i n P BS f or 60 m i n, and t hen a P BS sol ut i on cont ai ni ng DA was added t o br i ng t he f i nal concent r at i on to 1 µM. I n t hi s condi t i on, Fi g. 6.5 sh ows t he t i m e cour se o f t he r ef l ect i on spect ra when t he l i ght was i r r adi at ed t o t he i nt er f er omet er i mm er sed i n P BS sol ut i on. I m m edi at el y af t er t he DA addi t i on , no v ar i at i on was obser ved i n t he r ef l ect i on spect r um , but i t r ed -shi f t ed wi t h t i m e . Fi g s . 6.6a and 6. 6b sho w t he t i m e vs. peak -shi f t am ount of t he r ef l ecti on spect r um in t he condi t i ons between t he absence and pr esence of DA.
For t he scenar i o of i m m er si on i n PBS w i t hout DA, t he am ou nt of shi f t was appr oxi m at el y 2 nm , wher eas wi t h DA, t h e am ount of shif t i ncr ease d gr adual ly af t er 20 m i n of i mm er si on, and t he am ount of shi ft i ncr ease d by appr oxi m at el y 5 nm at 100 m i n. I n addi t i on, t he peak shif t per uni t t i m e i ncrease d 1.4- f ol d t o 0.0372 nm / m i n af t er DA was added , com par ed wi t h 0.0269 nm / m i n f or i m m er si on i n PBS wi t hout DA. Thi s suggest ed t hat DA was gr adual l y capt ur ed by t he t em pl at e i n t he PPy f i l m by t he DA addi t i on , and dur i ng t he exp ansi on pr ocess of t he PPy f i lm , com pr essi ve str ess was appl i ed t o t he def orm abl e m em br ane
1200 1300 1400 1500 1600 1700
Intensity (a.u.)
Raman shift (cm-1)
1200 1300 1400 1500 1600 1700
Intensity (a.u.)
Raman shift (cm-1) 1267
1486 1334
1416
1590
1200 1400 1600
Intensity (a.u.)
Raman shift (cm-1)
1200 1400 1600
Intensity (a.u.)
Raman shift (cm-1) 1335 1414
1590
1300 1500 1700
98
under neat h t he PPy f i l m , causi ng t he m em br ane def l ect i on. These r esul t s suggest ed t hat we obt ai ned t he spect r al r esponse due t o t he adsor pt i on of DA.
Fi gur e 6.4: Schem atic di agr am of experi ment al set up f or detecti ng def l ecti on of def or m abl e m em br ane caused by DA adsor p t i on t o t he t em pl at e.
Fi gur e 6.5: Ref l ecti on spect r al shi f t af t er dr oppi ng DA i n an i nt er f er om et er wit h a 5.45 µm ai r gap and a 50 µm di am et er.
Spectrometer (USB4000)
Stage Objective lens
(20x)
Sensor chip
Wavelength
Reflectance
PBS DA
(1 µM)
Peak shift Deflection
CCD camera (DP-22) Light source (LAX-C100)
Parylene CAu MIP film
500 0 550 600 650 700 750 800
0.2 0.4 0.6 0.8 1
Wavelength (nm)
Re fl ec ta nc e (a .u.)
Initial 27 min. later 105 min. later
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(a) (b)
Fi gur e 6.6: Ti m e cour se of t he am ount of p eak shi f t i n t he r ef l ect i on spect r um in an i nt er f er om et er with a 5.45 µm ai r gap and a 50 µm di am et er. ( a) Response t o i m m er si on i n PBS and ( b) r esponse t o a DA dr op at a fi nal concent r at i on of 1 µM.
However, si nce t he s hi f t am ount i n t he r efl ect i on spect r um due t o DA adsor pt i on was sm al l ( appr oximat el y 5 nm ) , a new i nt er f er om et er wi t h a n ai r- gap l engt h of 2.82 μm and a di am et er of 300 μm was f abr i cat ed t o im pr ove the r esponse, and t he MI P f il m s wer e f or m ed usi ng el ectr ochem i cal pol ym er izat i on under t he condi t i ons descr i bed i n Sect i on 6.4. Fi gs. 6.7 and 6.8 sh ow t he r ef l ecti on spect r a and t i m e cour se of t he spect r a when t he D A - cont ai ni ng PBS sol ut i on was added t o t he sensor chi p t o br i ng t he f i nal concent r at i on t o 1 µM af t er t he sensor chi p was i m m er sed i n PBS sol ut i on f or 180 m i n. Accor di ng t o t he r esul t , t he peak posi t i on of t he r ef lect i on spect r um di d not f l uct uat e at all dur i ng t he i m m ersi on i n PBS. For t he peak shi f t am ount , t he peak shi f t of t he spect rum i n absence of DA was obser ved t o be negat i ve by appr o xi m at el y 7 nm wi t hi n 15 m i n, and t hen i t appr oache d zer o. Thi s r esponse was consi der ed t o be caused by a change i n t he pr essur e of t he l i qui d dur i ng i m m er si on, whi ch cause d t he def orm abl e m em br ane t o t em por ar il y si nk and t hen r et ur n t o t he i ni t i al st at e. I n cont r ast , f or t he pr esence of DA, t he spect r um r ed - shi f t ed wi t h ti m e . For t he am ount of t he peak shi f t , we obser ve d a negat i ve shi f t of appr oxim at el y 3 nm i m m edi at el y aft er t he addi ti on , and a posi t i ve shi f t occur r ed af t er 16 m i n. Thi s r esponse was cons i der ed t o be due t o t he def or m abl e mem br ane t em poral l y sunk by l i qui d pr essur e, and t hen t he expansi on of t he PPy f i l m because of t he adsor pt i on of DA and t he i ncr ease i n t he Coul om b r epul si ve f or ce occur r ed. Bef o r e and af t er changi ng t he geom et r y par am et ers of t he i nter f er om et er, t he peak shi f t s t hat occurr ed wi t hi n 180 mi n af t er addi ng 1 μM DA wer e appr oxi m at el y 4 nm bef or e and appr oxi m at el y 25 nm
0 10 20 30 40 50 60
-2 -1 0 1 2 3 4 5
Time (min) Peak shift (nm) Slope
0.0269 (nm/min)
0 20 40 60 80 100 120
-2 -1 0 1 2 3 4 5
Time (min) Peak shift (nm) Slope
0.0372 (nm/min)
100
af t er t he change, and we co nf i r m ed t hat t he r esponse am ou nt i m pr oved by appr oxi m at el y 6.3 tim es. These r esul t s suggest ed t he possi bi li t y of l abel -f r ee det ect i on of neur ot r ansm i t t er s usi ng MEMS i nt er f er om et er wi t h MI P f i l m s .
(a) (b)
Fi gur e 6.7: Ref l ect i on spect r al shi f t i n an i nt er f er om et er wi t h a 2.82 µm ai r gap and a 300 µm di am et er. ( a) Response t o i m m er si on i n PBS and ( b) r esponse t o a DA dr op at a f i nal concent r at i on of 1 µM.
(a) (b)
Fi gur e 6.8: Ti m e cour se of t he am ount of p eak shi f t i n t he r ef l ect i on spect r um in an i nt er f er omet er wi th a 2.82 µm ai r gap a nd a 300 µm di am et er. ( a) Response t o i m m er si on i n PBS and ( b) r esponse t o a DA dr op at a fi nal concent r at i on of 1 µM.
0 30 60 90 120 150 180
-10 0 10 20 30
Time (min)
Peak shift (nm)
0 30 60 90 120 150 180
-10 0 10 20 30
Time (min)
Peak shift (nm)
0 0.2 0.4 0.6 0.8 1 1.2
400 500 600 700 800
Reflectance (%)
Wavelength (nm) Initial
40 min. later 80 min. later 120 min. later 180 min. later
0 0.2 0.4 0.6 0.8 1 1.2
400 500 600 700 800
Reflectance (%)
Wavelength (nm) Initial
40 min. later 80 min. later 120 min. later 180 min. later
0 0.2 0.4 0.6 0.8 1 1.2
400 500 600 700 800
Reflectance (%)
Wavelength (nm) Initial
40 min. later 80 min. later 120 min. later 180 min. later
0 0.2 0.4 0.6 0.8 1 1.2
400 500 600 700 800
Reflectance (%)
Wavelength (nm) Initial
40 min. later 80 min. later 120 min. later 180 min. later
Chapter 6. Detection of neurotransmitter by MEMS interferometer with molecularly imprinted polymer
101 6 . 7 C o n c l u s i o n
I n t hi s chapt er, t o det ect sm al l neurot r ansm it t er s i n t he cavi t y - seal ed i nt er f er om et er, a mol ecul ar l y im pr i nt ed pol ym er ( MI P) , whi ch can adsor b neur ot r ansm it t er s, i s int r oduced . A f abr i cat i on pr ocedur e f or t he f or m at i on of MIP on t he i nt er f er om et er was pr oposed, and a PPy f i l m wi t h a t em pl at e of t he neur ot r ansm it t er DA was f or m ed on t he f abr i cat ed i nt er fer om et er usi ng el ect r ochemi cal pol ym er i zati on. I n addi t i on, Ram an spect r oscop y was per f or m ed t o conf i rm t he f or mat i on of DA t em pl ates i n t he PPy fi l m . I n t hi s sam pl e, di ff er ences i n t he spect r al r esponses wer e obt ai ned i n t he pr esence and absence of DA, suggest i ng t he possi bi li t y o f det ect i ng sm al l neur ot r ansm i t t er s. The key poi nt s of t hi s chapt er ar e as f ol l ows:
【Fabr i cat i on and exper i m ent al r esul t s】
1. An 80 nm - t hi ck MI P f i l m ( PPy) cont aini ng t he DA was f or m ed usi ng el ect r ochemi cal pol ym er i zati on ont o t he i nt er f er om et er wi t h t he cavi t y - seal ed st r uct ur e.
2. Usi ng Ram an spect r oscop y, DA and PP y - der i ved peaks wer e obser ved i m m ediat el y af t er impr i nt i ng DA, and onl y PPy - der i ved peaks wer e obser ved af t er i m m er si on i n ethanol , suggest i ng t hat t he im pr i nt ed DA was r em oved f r om PPy and t he DA t em pl at es wer e f or m ed.
3. Af t er i mm er si ng t he sensor chi p wi t h DA t em pl at es i n PBS, t he t i m e cour se of t he r efl ect i on spectr a was obt ai ned when t he DA - cont ai ni ng PBS was added t o m ake t he f i nal concent r at i on 1 µM. As a r esul t , t he peak shi ft per uni t ti me i ncr eased 1.4 t i m es to 0.0372 nm / m i n af ter DA was added , co m par ed wi t h 0.0269 nm / m i n when t he s am pl e was i mm er se d i n PBS wi t hout DA.
4. We conf i r m ed t hat the sensor r esponse of DA at a concent r at i on of 1 µM i ncr eased by 6.3 - f ol d by changi ng t he geom et r y par am et er s of t he i nt er f er om et er.
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