- 學位論文
電/熱藥物經皮吸收系統與無線射頻葡萄糖感測系統整合探討
Integration studies of electroporation/thermal transdermal delivery system and RF-based glucose sensing system
摘要
本研究之目的為整合電/熱經皮吸收系統與無線射頻葡萄糖感測系統，期許能使用非侵入式的方式對糖尿病患的血糖進行檢測與調控。電/熱經皮吸收系統可提供電穿孔與熱輔助兩種物理作用，用以促進胰島素經皮吸收；無線射頻葡萄糖感測系統則由體外傳輸子系統與體內感測子系統組成，兩子系統可相隔皮膚進行訊號傳輸，以此進行非侵入的血糖檢測，而後經由RF模組將訊號傳輸至電/熱經皮吸收系統進行顯示。已完成之電/熱經皮吸收系統可使用電池驅動，並設置於特製機構中，使系統功能得以精準作用於指定區域中，此外，電穿孔功能可於45秒後輸出穩定且精確的高壓脈波，而熱輔助功能可於人體表面皮膚加熱7秒後到達40 ℃，並可維持溫度於40~41 ℃。無線射頻葡萄糖感測系統的傳輸實驗結果顯示，體外傳輸子系統與體內感測子系統有9 mm的垂直傳輸距離，兩子系統之載波頻率為13.56 MHz；體外傳輸子系統與電/熱經皮吸收系統有260 cm的傳輸距離。系統的整合驗證中，使用豬皮進行擴散槽實驗以模擬胰島素經皮吸收進入體內之現象，並使用人類肝癌細胞(HepG2)模擬體內環境，使細胞藉由胰島素提升葡萄糖之使用量，降低細胞環境之葡萄糖濃度，過程佐以市售血糖機檢測葡萄糖濃度，以對照體內感測子系統所感測之葡萄糖訊號。由實驗結果顯示，電穿孔可有效改變豬皮的滲透效率，並使電阻抗特性下降6.24 ~ 31.5 %，使用電穿孔與熱輔助則可令胰島素經皮吸收的效果提升33倍，以此結果與細胞共培養，可發現細胞使用葡萄糖的效率提升1.8 ~ 7.7 %。總言之，本研究已成功結合電/熱經皮吸收系統與無線射頻葡萄糖感測系統，並透過體外模擬實驗驗證其初步功能性，具有應用於糖尿病患血糖監控之潛能。
並列摘要
This study is to integrate a transdermal insulin delivery system and a glucose sensing system to provide a non-invasive method for glucose control in diabetic patients. The transdermal insulin delivery system provides electroporation and heat energy to enhance insulin delivery through the skin. The glucose sensing system contains an external signal receiver and an implanted glucose sensor which can monitor glucose signals continuously. These signals are transmitted with radiofrequency. The transdermal insulin delivery system is powered by a battery and the whole system is small and portable. The system is confined to a specific sliding device which can act in different working area for electroporation or heating on the skin. The electric pulse can fire in 45 sec and the temperature can increase to 40 ℃ in 7 sec and can keep constant within 1 ℃. The working distance of radio frequency-based glucose sensing system is 9 mm from the skin with a 13.56 MHz carrier frequency. The working distance of the external receiver and insulin delivery system is 260 cm. We verified the systems with drug diffusion chamber using isolated porcine skin and HepG2 cells for glucose utilization to mimic human body. A blood glucose monitor in the market was used for comparison. The results show drug delivery system can reduce 6.24% to 31.5% of the skin resistance and enhancing insulin transdermal delivery to 33-fold. The glucose utilization in HepG2 cells increased 1.8-7.7% after insulin delivery. In conclusion, this study has successfully integrated an insulin transdermal delivery system and a radio frequency-based glucose sensing system. The system was verified with ex vivo and cell culture methods. This systems may have clinical potential in diabetic patients.