植入式实验动物血糖动态监测装置的设计

An implantable blood glucose monitoring device for laboratory animals

目的 设计、研制一种用于实验动物的全植入式血糖浓度检测系统,通过一次植入手术可获得实验动物自然状态下经无线方式传输的动态血糖监测数据.方法 监测系统包括植入体和体外接收端两部分.植入体尺寸设计为11.5 mm×16.0 mm×5.0 mm,不超过实验大鼠体积的1/10.以SOF-SENSOR植入式葡萄糖传感器及其外围三电极伏安测量电路为核心,采用锂电池和稳压芯片构建供电,测量数据通过CC2540低功耗蓝牙系统芯片无线传输至体外.植入体外层包裹医用硅胶材料,以保护电路和提高植入体生物相容性.结果 体外验证实验表明,本系统可在2～34 mmol/L范围较准确地测量葡萄糖浓度（r=0.996 7）,平均标准误差为0.193 mmol/L,灵敏度为9.24 nM（mmol/L）,能够满足设计要求.结论 植入式实验动物血糖动态监测装置体积小,适合植入.体外血糖测量验证实验表明本装置的血糖测量范围、准确性、灵敏度及标准误差等均能满足设计要求.此装置有望为糖尿病病理和药效学研究提供重要的技术支持.

Objective To design a fully implantable blood glucose concentration detection system used for laboratory animals,to get measurement data of blood glucose which can be transmitted wirelessly when animals are in nature state.Methods The system included in vivo and in vitro part.The implant included an implantable glucose sensor SOF-SENSOR with three electrodes volt-ampere circuit as the core of the module,and power supply module adopted lithium battery and voltage chip,while the wireless data transmission unit used CC2540 chip.In vivo part was coated by medical silica to make it safe and biocompatible.Results The final mechanical size of the implant was 11.5 mm×16.0 mm×5.0 mm,which was less than one tenth of the volume of laboratory rat and satisfied the design requirements.The results of the in vitro studies showed that the effective measuring range of the system was 2-34 mmol/L （r=0.996 7）,and the average standard error of measurement was 0.193 mmol/L with the sensitivity of 9.24 nA/（mmol/L）.The system was proved to meet all the design requirements.Conclusions The size of the dynamic blood glucose monitoring system is small enough to be implanted fully subcutaneously in laboratory animals.The device is proved in accordance with design and standards by in vitro experiment in range of measurement,accuracy,sensitivity and standard error.The system may provide a significant technical support for the study on diabetes pathogenesis and pharmacodynamics.