第 3 章

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第 3 章. 生醫感測器. 3.1.1 生醫感測器的定義. 傳統生化分析或生物檢驗技術係指利用生化或免疫學原理,以各種化學藥劑、酵素、抗體或抗原等與檢體 ( 例如血液、尿液 ) 中之待測物質 ( 例如葡萄糖、尿素氮、膽紅素、尿酸、膽固醇、肌酸酐及乳酸等 ) 作用,經一系列設計之生化反應,並配合各種光學或電極之訊號檢知器及資料處理系統來測定物質濃度。. 配合微小化所衍生的生醫感測器,不僅可以置入診療儀器中分析微量物質,更可能植入人體中用以追蹤生化物質或藥物的濃度,提供即時資料給醫療人員做為診治參考,而且又可製造成操作簡便、可攜帶的居家必備醫療用品。. - PowerPoint PPT Presentation

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  • 3.1.1 () ()

  • 3.1.2 1962ClarkLyons (biosensor)

  • (recognition element) (transducer) (acquisition system)

  • Surface modifications

    Nanowires + Transistor

    (NWFET

  • ()

  • (quartz crystal microbalance, QCM) (serial piezoelectric quartz crystal, SPQC) (surface acoustic wave, SAW)

  • (enthalpy)

  • 3.1.3

  • 3.2 (biotics) (abiotics) (bioaffinity) (biocatalytic)lectinsavidin/biotin

  • 3.2.2

  • (1) (2) (3) (4)

  • 1. (van der Waals force)

  • 2.3. (NH2) (COOH) (SH) (OHCRCHO)

  • 4.5. (entrapment) 6. (cross-linking)

  • 3.2.3

  • OHOHHOR (R)

  • (self-assembled monolayer)

  • (plasma)

  • 3.2.4

  • H2O2H2O2 (Glucose oxidase, GOD) (lactate oxidase, LOD) (uricase) (cholesterol oxidase) (choline oxidase) H2O2 PtPdPd/AuH2O2 H2O2 H2O2

  • 3.3.1 ()

  • (b)(a)

  • ()

  • ()

  • ()

  • 3.3.2

  • (quasi-equilibration) (working electrode) (counter electrode) 0 (Wk Ref)

  • NernstNernst

  • () (1 M)

  • Gibbs

    n (2) (96487 Cmol-1)E0Gibbs(G)

  • /

    /

  • 1125CGibbs0G0EH0=010

  • + 0.34 V

  • (linear sweep voltammetry, LSV) (initial potential,Ei) (end potential,Ef) (scan rate,v)LSV (ifar) (ichg) (iads) (ibkg)

  • (a) (b)

    (b)

    C

    B

    A

    Ep/2

    E1/2

    ip

    Ep

    (a)

    Ei

    Ef

  • LSV

  • (+ / -)E0E0E1/2

  • (EP) (Ox/R) (couple)

    Ep/2

  • (cyclic voltammetry, CV)

    (b)

    EMBED Equation.3

    (a)

    _1246271786.unknown

  • (a)0.1MNaOHCV(b)(NaOH,KC1,H2SO4)

    Au

    GC

    Pt

    Au-NaOH

    Au-KCl

    Au-H2SO4

    (a)

    (b)

  • (a)

  • (b)

  • 3.10

  • (Ox) (Red) (Eeq) (3-19)

  • E25C1 Ma () (C) 1

  • E

    E

    E

    M + + e- M

    M + + e- M

    M + + e- M

    Eeq

  • (Fermi level) (E) E>EeqEeq=E

  • n e-

    Redbulk

    Oxbulk

    Red

    Redsurf

    Oxsurf

    Ox

    Redads

    Oxads

  • (cyclic voltammetry, CV)

  • i V (a) (b)

    (b)

    (a)

    i

    V

    V

    i

  • (planar electrode) (semi-infinite linear diffusion)Cottrell (I(t)) (t)

  • (semi-infinite spherical diffusion)

    0

  • Clark

  • Clark

    Pt

    Ag

  • (electrochemical impedance spectroscopy, EIS) () (affinity)

  • (1)

    ViV0Vmi0Im (rad/s)R (resistance)X (reactance)Z

  • RsCdlRetZw

    ne-

    Red

    Rs

    Cdl

    Zw

    Red

    Ox

    Red

    Ox

    -

    -

    -

    -

    -

    -

    -

    -

    -

    -

  • Faraday

  • abc0

    Rs

    Ret

    Zre/

    (0

    c

    b

    a

    (

    -Zim/

  • (2)BodeNyquistNyquist

  • (3) (constant phase element, CPE)

  • Bode plotNyquist plot(a)(b)

  • Bode plotNyquist plot(d)(c)

  • 01Nyquist plot1Nyquist plotCPE

  • Nyquist plot

  • 3.4.1 (ion-sensitive field effect transistor, ISFET) 1970 Bergveld(metal-oxide-semiconductor field effect transistor, MOSFET)ISFETMOSFETISFETISFET

  • ISFETSiO2Si3N4 Al2O3 Ta2O5 SnO2-WO3 -Si:HAlNPbTiO3 ISFET

  • (a)--(b)

  • ISFET CMOS

  • 3.4.2 (extended gate field effect transistor, EGFET)ISFETEGFETMOSFETEGFETMOSFET

  • -

  • 3.4.4 (temperature effect) (drift effect) (hysteresis effect)

  • ISFET(1)(2)(3)(4)

  • ISFETISFET

    V0ISFETTIDS Eref0VT*ISFET

  • ISFETpHpH ( (Nernst) 25C59.16 mV/pH)

  • ISFETISFETISFETpHH+OH-H+OH-pHOH-

  • (a)(b)

    xh

    xh

    (b)

    (a)

    s

    x

    M

    -

    -

    +

    +

    Solution

    Membrane

  • ISFET

    Time

    H

    pHx

    pHz

    pHy

    pHx

    V1

    0

    V2

  • 3.5 (electromagnetic radiations) (gamma ray) (radio wave)

  • (a)(b)

  • 3.5.1 1. (wave) (quantum)

  • (photon)(E)()()E=hc/=hhPlanck(6.6310-34Js) c(=3108m/s) Extz, k( )E0c

  • 2. (reflection) (refraction) (transmission) (photoemission) (thermal)

  • 3.cvnn=c / v () (dispersion) (Snells law of refraction)

    ()clBeer Lambert( ) (absorption coefficient)

  • 3.5.2 1.UV-VIS

  • 2.IR

  • 3.5.3 (Rayleigh) Mie

  • (Nephelometry)

  • (photon) (optical phonon) IR

  • (a) (b)

  • 3.5.4 (absorption) (emission) (Stokes shift )

  • Jablonski

  • 3.5.5 1. (surface plasmon) (surface plasmon resonance, SPR) 100200 nm () SPR ()

  • (dielectric constant,) (m) (b) SPRSPR(1)SPR ()(2)SPR ()(3)SPR ()(4)SPR ()

  • 2. (two photon microscopy)10-15

  • 3. (fluorescence correlation spectroscope, FCS) ()

  • Observation volume

    t5

    t4

    t3

    t2

    t1

    t6

    time

    F(t+)

    time

    F(t)

    7.5nM FITC

  • 3.6.1 (piezoelectric substrate, PZT)

  • (dipole) (polarization)

  • 3.6.2 1. (thickness-shear-mode (TSM) resonators) (bulk acoustic waves, BAW) (resonant frequency)

  • (quartz crystal) AT

    F (Hz)FM (g)A (cm2)

  • 2. (surface-acoustic-wave (SAW) sensors) (piezoelectric substrate) (piezoelectric film) (interdigital transducers, IDTs)IDT IDT

  • SAW Hz0.01Hz MHz GHz

  • Piezoelectric substrate

    Input transducer

    Output transducer

    SAW

  • 3. (flexural-plate-wave (FPW) resonators)PZT

  • (FPW)

    IDT

    PZT

    Membrane

    Ti/TiN/Pt

    Si wafer

    Silicone Nitride/Oxide

  • 3.6.3