Oliver Nick, Georgiou Pantelis, Johnston Desmond, Toumazou Christofer
Institute of Biomedical Engineering, Imperial College, London, UK.
J Diabetes Sci Technol. 2009 Nov 1;3(6):1419-24. doi: 10.1177/193229680900300623.
The normal pancreatic beta-cell membrane depolarizes in response to increasing concentrations of glucose in a bursting pattern. At <7 mM (126 mg/dl), the cell is electrically silent. The bursting pulse width increases as glucose rises >7 mM (126 mg/dl) until a continuous train of bursting is seen at >25 mM (450 mg/dl). A bio-inspired silicon device has been developed using analogue electronics to implement membrane depolarization of the beta cell. The device is ultralow powered, miniaturized (5 x 5 mm), and produces a bursting output identical to that characterized in electrophysiological studies.
The goal of this study was to demonstrate the ability of silicon implementation of beta-cell electrophysiology to respond to a simulated glucose input and to drive an infusion pump in vitro.
The silicon device response to a current source was recorded at varying simulated glucose concentrations. Subsequently, the bursting response to a changing analyte concentration measured by an amperometric enzyme electrode was converted to a voltage, driving a syringe pump loaded with a 50-ml syringe containing water.
Bursting responses are comparable to those recorded in electrophysiology. Silicon beta-cell implementation bursts with a pulse width proportional to concentration and is able to drive an infusion pump.
This is the first in vitro demonstration of closed loop insulin delivery utilizing miniaturized silicon implementation of beta-cell physiology in analogue electronics.
正常胰腺β细胞膜会随着葡萄糖浓度升高以爆发模式去极化。当葡萄糖浓度<7 mM（126 mg/dl）时，细胞电沉默。当葡萄糖浓度>7 mM（126 mg/dl）时，爆发脉冲宽度随着葡萄糖浓度升高而增加，直到在葡萄糖浓度>25 mM（450 mg/dl）时出现连续的爆发序列。一种受生物启发的硅器件已被开发出来，它利用模拟电子技术实现β细胞的膜去极化。该器件功耗超低、体积小巧（5×5毫米），并产生与电生理研究中所描述特征相同的爆发输出。
本研究的目的是证明硅实现的β细胞电生理对模拟葡萄糖输入作出反应并在体外驱动输液泵的能力。
在不同模拟葡萄糖浓度下记录硅器件对电流源的响应。随后，将通过安培酶电极测量的对变化分析物浓度的爆发响应转换为电压，驱动一个装有50毫升水的注射器的注射泵。
爆发响应与电生理记录的响应相当。硅β细胞实现以与浓度成比例的脉冲宽度爆发，并且能够驱动输液泵。
这是首次在体外证明利用模拟电子技术中β细胞生理学的小型化硅实现进行闭环胰岛素输送。
