結合奈米碳管電極之電化學生醫感測平台及其應用於奈米抗生素膠囊臨床前藥物釋放特性評估

An Electrochemical Biosensing Platform Using Carbon Nanotubes Electrodes for Preclinical Evaluation of Drug Release Profile of Antibiotic Nanocapsules

王智瑩(Chih-Ying Wang)

指導教授 ： 洪建中

國立清華大學/工學院/動力機械工程學系/碩士(2010年)

摘要

在本論文研究中，開發與設計一套可用於微量、即時連續量測且適用於抗生
素奈米膠囊藥物釋放監測之奈米碳管電極式的電化學生醫感測平台。本研究首先
以微機電技術設計製作電化學感測電極與微流體晶片，並以檢測電路與虛擬控制
系統，進行感測訊號最佳化處理；最後以所研發之奈米碳管電極電化學生醫感測
平台應用於奈米抗生素膠囊藥物釋放臨床前評估探討。
電化學生醫感測平台中，電極的設計為影響感測訊號的關鍵元件之一，電極
材料與表面結構特性在生醫感測訊號上有重大影響。本研究結合奈米碳管於電化
學生醫感測器上，使用電泳或液滴塗佈方式將奈米碳管修飾在金電極表面，成功
提升電極強度及訊號放大能力，可承受最大電流從 0.0208 mA 提升至 0.6680
mA；訊號放大能力於 1/ml 抗生素濃度條件下，由 0.0222 mA 放大至 0.3051
mA，訊號放大 13.75 倍。抗生素純藥測試所建立的校正曲線線性回歸係數為
R2=0.9837，線性濃度範圍 1~ 10 g/ml，靈敏度為 0.023 mA‧ml/g。
傳統 HPLC 等大型儀器無法連續且即時量測奈米抗生素膠囊釋放狀況，本研
究所開發之結合奈米碳管電極的電化學生醫感測平台，在抗生素奈米膠囊的連
續釋放量測中，量得抗生素奈米膠囊於第 4 天開始啟動藥物釋放，釋放速率為
0.0258g/ml．hr，至第七天累積釋放濃度達 24.98 g/ml。以本論文所研究開發
之結合奈米碳管電極的電化學生醫感測平台可提供奈米藥物膠囊開發合成過程
的調整依據，同時也提供臨床前用藥資訊，提供在動物試驗上也無法獲得之局
部即時濃度值，增進奈米藥物膠囊開發速度，及降低未來臨床試驗風險。希望
藉由整合電化學奈米碳管電極設計與檢測平台，於臨床前針對奈米抗生素膠囊
藥物釋放特性作感測評估。未來可進一步整合被動式無線傳輸系統，植入在動
物體中，做長期藥物釋放監控。

關鍵字

奈米碳管 ； 電化學

並列摘要

ii
ABSTRACT
In this thesis, an electrochemical biosensing platform using carbon nanotubes
electrodes, which can be used to evaluate drug release profiles of antibiotic
nanocapsules in real time and continuous mode, has been successfully designed,
developed, and characterized. First, the electrochemical sensing electrode has been
fabricated by MEMS technologies. Then, the biosensing platform is connected to the
sensing circuit and LabVIEW program for signal acquire and processing. Finally,
the developed carbon nanotubes electrode and electrochemical biosensing platform
have been applied for pre-clinical evaluation of drug release profiles of antibiotic
nanocapsules.
The electrode is one of the key components for electrochemical sensing. The
materials and the surface characteristics of electrodes play an important role in
electrochemical sensing. Here, we successfully combined the carbon nanotubes
electrodes with electrochemical biosensor, using electrophoresis deposition or
drop-coating method to deposit carbon nanotubes on the surfaces of the gold
electrodes. The measurement results show that the maximum affordable current has
been improved 0.0208 mA to o.6680 mA. And, the sensing signals are amplified up to
13.75 times using carbon nanotube-modified electrodes. The linear range of the
developed electrochemical biosensing platform using carbon nanotubes electrodes is
from 1 g/ml to 10g/ml (R2=0.9837). The sensitivity of the developed system is
0.023 mA‧ml/g.
The HPLC and other traditional instrument could not detection the drug release
from nanocapsules in real time and continuous mode. According to the measurements
using our developed electrochemical biosensing platform, it shows that antibiotic nanocapsules start to increase the drug release on the 4th day and the release rate is
0.0258 μg/ml．hr. The drug release of antibiotic nanocapsules reached 24.98
μg/ml on the 7th day.
The antibiotic biosensor platform using carbon nanotube electrodes for
preclinical evaluation of drug release profile of nanocapsules presented in this work
showed good performance in sensing of antibiotic Teoplanin drug samples. The
antibiotic biosensor platform could be further integrated with a micro fluidic platform
for controlled synthesis of nanocapsules to feedback the drug release profile for
optimization of the synthesis process. In addition, the developed biosensor can be
integrated with wireless passive transmission module to be an implantable biomedical
microsystem for health monitoring in future.

參考文獻

Polyanhydrides for Antibiotic Drug Delivery: In Vivo Osteornyelitis Treatment

from polymethylmethacrylate beads. An experimental and pharmacokinetic

[4] G. Gregoriadis, "Engineering liposomes for drug delivery: progress and

problems",Trends in Biotechnology, vol.13, pp.527–537, 1995.

[5] G. S. Kwon, K. Kataoka, "Block copolymer micelles as long-circulating drug