Electrical & Computer Engineering, University of Connecticut, Storrs, CT 06269, USA.
Biomed Microdevices. 2013 Feb;15(1):151-60. doi: 10.1007/s10544-012-9708-x.
Implantable sensors for continuous glucose monitoring hold great potential for optimal diabetes management. This is often undermined by a variety of issues associated with: (1) negative tissue response; (2) poor sensor performance; and (3) lack of device miniaturization needed to reduce implantation trauma. Herein, we report our initial results towards constructing an implantable device that simultaneously address all three aforementioned issues. In terms of device miniaturization, a highly miniaturized CMOS (complementary metal-oxide-semiconductor) potentiostat and signal processing unit was employed (with a combined area of 0.665 mm(2)). The signal processing unit converts the current generated by a transcutaneous, Clark-type amperometric sensor to output frequency in a linear fashion. The Clark-type amperometric sensor employs stratification of five functional layers to attain a well-balanced mass transfer which in turn yields a linear sensor response from 0 to 25 mM of glucose concentration, well beyond the physiologically observed (2 to 22 mM) range. In addition, it is coated with a thick polyvinyl alcohol (PVA) hydrogel with embedded poly(lactic-co-glycolic acid) (PLGA) microspheres intended to provide continuous, localized delivery of dexamethasone to suppress inflammation and fibrosis. In vivo evaluation in rat model has shown that the transcutaneous sensor system reproducibly tracks repeated glycemic events. Clarke's error grid analysis on the as-obtained glycemic data has indicated that all of the measured glucose readings fell in the desired Zones A & B and none fell in the erroneous Zones C, D and E. Such reproducible operation of the transcutaneous sensor system, together with low power (140 μW) consumption and capability for current-to-frequency conversion renders this a versatile platform for continuous glucose monitoring and other biomedical sensing devices.
用于连续血糖监测的植入式传感器在优化糖尿病管理方面具有巨大潜力。但这通常会受到以下各种问题的影响：（1）组织的负面反应；（2）传感器性能不佳；以及（3）缺乏可减少植入创伤的设备小型化。在此，我们报告了构建一种可同时解决上述三个问题的植入式设备的初步结果。在设备小型化方面，采用了高度小型化的 CMOS（互补金属氧化物半导体）电位计和信号处理单元（总面积为 0.665 平方毫米）。信号处理单元将经皮、克拉克型电流型传感器产生的电流转换为线性输出频率。克拉克型电流型传感器采用五层功能层的分层结构，以实现良好的质量传递平衡，从而使传感器在 0 至 25 毫摩尔葡萄糖浓度范围内产生线性响应，远远超过生理观察范围（2 至 22 毫摩尔）。此外，传感器还涂有一层厚厚的聚乙烯醇（PVA）水凝胶，其中嵌入了聚乳酸-共-羟基乙酸（PLGA）微球，旨在提供持续的局部地塞米松输送，以抑制炎症和纤维化。在大鼠模型中的体内评估表明，经皮传感器系统可重复跟踪反复的血糖事件。对所获得的血糖数据进行 Clarke 误差网格分析表明，所有测量的血糖读数均落在所需的 A 区和 B 区，而无一落在错误的 C 区、D 区和 E 区。经皮传感器系统的这种可重复操作，以及低功耗（140 微瓦）和电流到频率转换的能力，使其成为连续血糖监测和其他生物医学传感设备的多功能平台。
