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3.1 Generation and characterization of gold nanoparticles

AuNPs could be synthesized by Turkevich-Frens citrate reduction method [71] and

characterized by determining the visible light absorbance spectra between the wavelengths of

700 nm and 400 nm. The particle size and the concentration of AuNPs could be determined

via their peak wavelength and peak absorbance. The concentration of AuNPs could be

calculated based on the Beer’s law (A = ελbc). Where, ελ equals to 1.25 x 109 cm-1 M-1 for 20

nm AuNP solution with O.D. of 1.0. The generated AuNP under 2 mM sodium citrate

exhibited a peak absorption at 518 ~ 520 nm.

The concentration of AuNPs was approximately 1.4 nM. Interestingly, the particle size of

AuNPs was affected by the concentration of sodium citrate. The negatively charged citrate

ions may coated on the surface of AuNPs forming a negatively charged layer. Hence, AuNPs

are more prone to rejection and difficult to attract each other, resulting in the formation of

gold nanoparticles smaller particle size [72].

When surface modified, the absorbance and the color of colloidal AuNPs changed

markedly. This phenomenon will be used to characterize the surface-functionalized AuNPs.

3.2 Generation and characterization of cysteamine-AuNPs

Cysteamine (CNH2) contains a sulfhydryl group (-SH), which is relative active and is

readily oxidized to form disulfide bonds or to form a covalent bond with various metals,

especially gold, under room temperature. The modification of AuNP with CNH2 may

functionalize its surface with amine groups. However, when generating CNH2-coated AuNPs

(CNH2AuNP) under the high concentration of CNH2 the aggregation of AuNPs may be

increased due to the hydrophobic property of the CNH2 under the neutral condition. The

amine group of CNH2 has a dissociation constant of around 10 making it nearly neutral under

pH 7.0. To prevent the possible occurrence of aggregation and precipitation of CNH2AuNP

different ratios of AuNPs and CNH2 was prepared and incubated at room temperature for two

hours. As shown in Figure 3, when the mole ratio of CNH2 to AuNPs was 2500:1 the

generated CNH2AuNPs exhibited the pink color with the absorption peak of 522 ~ 524 nm;

whereas, when the mole ratio increased to 3000:1 the generated CNH2AuNPs exhibited the

purple color with the absorption peak of 526 ~ 535 nm. Further study was performed by

determining the absorption peak and absorbance of the generated CNH2AuNPs. The AuNPs

without modification exhibited an absorption peak at 518 nm. The CNH2AuNPs synthesized

under the condition with CNH2 and AuNPs in a mole ratio of 2500:1 exhibited an absorption

peak of 524 nm (Figure 4) with estimated particle size of 20 nm. In comparison, the

CNH2AuNPs synthesized under the condition with CNH2 and AuNPs in a mole ratio of

3000:1 exhibited an absorption peak of 535 nm (Figure 5) with estimated particle size of 50

nm. Apparently, the aggregation between the CNH2AuNPs might occur under the higher mole

ratio of CNH2 and AuNPs. Accordingly, the mole ratio of CNH2 to AuNPs at 3000:1 was

adopted for the production of CNH2AuNPs, which exhibited the absorbance peak at 526 nm

(CNH2 and AuNPs concentration increased tenfold) and the concentration of 0.6 nM. The

particle size of CNH2AuNP also depends on the reaction time between the CNH2 and AuNPs.

The size of CNH2AuNPs is larger with longer reaction time. Therefore, the reaction time of 2

hours was set for the generation of CNH2AuNPs.

3.3 Preparation of diazonium salt-coated SPCE

In this study the aryl diazonium was used as the linker for the immobilization of AuNPs

and enzymes. Prior to the aryl diazonium modification the surface of SPCE was treated with

oxygen plasma under the condition of 25 W for 30 sec, followed by cyclic voltammetric

treatment within the scanning range of -1.0 ~ 1.0 V and scanning rate of 100 mV/s for 10

cycles. The surface cleaning with oxygen plasma may remove surface impurities and lead to

increasing hydrophilicity of the electrode surface [58]. The electrochemical reaction could be

facilitated after surface cleaning.

The electrodeposition of diazoted CMA on the surface of SPCE was performed by

immersing oxygen plasma-cleaned SPCE in CMA stock solution (Figure 7) and run cyclic

voltammetric scanning within the range of -0.7 and +0.8 V at a scan rate of 200 mV/s. After

electrodeposition the CMA-coated SPCEs were immersed in pH 7, PBS buffer and stored at

4ºC before use (Figure 8).

The CMA-electrodeposited SPCE was characterized by the pH-dependency of the

electrochemical responses. The pKa of the acryl carboxylic acids (-COOH) is probably

around 4-5. Hence the CMA-deposited SPCE exhibited a pH-dependent electrochemical

response to [Fe(CN)6]3¯ due to the differential ionic status of CMA under different pH values.

It is neutral under pH 2.0 and negatively charged at pH 7.0. With bare SPCE the cyclic

voltammograms of 1 mM K3[Fe(CN)6] in pH 2.0 and pH 7.0, PBS buffers were similar

(Figure 9A), suggesting no pH-dependent effect. However, with CMA-modified SPCE the

cyclic voltammograms of 1 mM K3[Fe(CN)6] in pH 2.0 exhibited clear redox peaks at 0.15 V

and 0.3 V (Figure 9B, red line); whereas, at pH 7.0 the redox peaks of the cyclic

voltammogram were almost invisible (Figure 9A, blue line). This result suggests that the

redox reactions of [Fe(CN)6]3¯ in pH 7.0, PBS buffer were largely abolished presumably due

to the repelling effect of the negatively charged CMA group to the anionic ion [Fe(CN)6]3¯at

pH 7.0.

3.4 Characterization of AuNP-modified CMA/SPCE

The modification of CMA/SPCE with AuNPs and CNH2AuNPs was illustrated in Figure

10. The CNH2AuNP contains an amine group (-NH2), which is helpful for the immobilization

of other substances. The electrochemical properties of the AuNP- or CNH2AuNP-modified

SPCE were determined by their electrochemical responses to H2O2. The cyclic voltammetry

of bare SPCE, CMA/SPCE, AuNP/CMA/SPCE and CNH2AuNP/CMA/SPCE without H2O2

was shown in Figure 11. The basal responses of SPCE increased with the modification of

AuNP and CNH2AuNP.

The electrochemical responses of bare SPCE, CMA/SPCE, AuNP/CMA/SPCE and

CNH2AuNP/CMA/SPCE to 500 µM H2O2 were also determined (Figure 12). The

electrochemical current of SPCE to H2O2 was also increase following the modification of

AuNP and CNH2AuNP. The current-time responses of bare SPCE, CMA/SPCE,

AuNP/CMA/SPCE and CNH2AuNP/CMA/SPCE to H2O2 were 3.97 x 10-8, 4.36x 10-8, 7.05 x

10-8, 7.18 x 10-8A/500 µM H2O2 (Figure 13). This result suggests that gold nanoparticles or

modified gold nanoparticles could significant increase electrochemical responses. The Figure

14 shows the does-current response of bare SPCE, CMA/SPCE, AuNP/CMA/SPCE and

CNH2AuNP/CMA/SPCE to various concentration of H2O2. The sensitivity of bare SPCE,

CMA/SPCE, AuNP/CMA/SPCE and CNH2AuNP/CMA/SPCE to H2O2 was 7.94 x 10-6, 8.72

x 10-6, 1.41 x 10-5, 1.44 x 10-5 A/cm2/mM (Figure 15), respectively.

The effect of particle size of AuNPs (40 nm and 50 nm) in the electrochemical responses

to H2O2 was further studied (Figure 16). As shown in Figure 16, the larger of the AuNP (50

nm) exhibited higher electrochemical response to H2O2 (7.28 x 10-5A / cm2 / mM H2O2) than

that of smaller AuNPs (40 nm) (6.6 x 10-5A /cm2 / mM H2O2), suggesting that electrochemical

responses of SPCE also affects electrochemical response.

3.5 Development and characterization of GOx electrode

In this thesis, two types of glucose biosensors were developed using AuNP-coated SPCE:

(i) the CMA/SPCE coated with the mixture of GOx and CNH2AuNPs, termed GOx-

CNH2AuNP/CMA/SPCE (Figure 17A) and (ii) CMA/SPCE was sequentially coated with

CNH2AuNPs and GOx to generate the GOx/CNH2AuNPs/CMA/SPCE (Figure 17B). The

CNH2AuNPs-modified and GOx–CMA/SPCE electrodes were used as controls. In

comparison the GOx–CMA/SPCE, GOx- CNH2AuNP/CMA/SPCE and

GOx/CNH2AuNPs/CMA/SPCE exhibited the electrochemical response to 0.5 mM glucose of

8.12 x 10-7, 9.88 x 10-7, 1.44 x 10-6 A/cm2/mM glucose, respectively (Figure 19). This result

suggests that GOx/CNH2AuNPs/CMA/SPCE exhibited a response higher than that of

GOx-CNH2AuNPs/CMA/SPCE [73]. The sensitivity of GOx–CMA/SPCE, GOx-

CNH2AuNP/CMA/SPCE and GOx/CNH2AuNPs/CMA/SPCE to glucose was 8.12 x 10-7,

9.88 x 10-7, 1.44 x 10-6 A/cm2/mM, respectively. The dose-current response of electrodes to

glucose was performed under different concentrations of glucose (0.5, 1, 1.5 and 2 mM)

(Figure 18). The result showed that the GOx/CNH2AuNPs/CMA/SPCE was better than that of

other two GOx electrodes. There was no responses to glucose on the

CNH2AuNPs/CMA/SPCE (data not shown).

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