Luo Xiaojin, Yu Qi, Yang Li, Cui Yue
School of Materials Science and Engineering, Peking University; First Hospital Interdisciplinary Research Center, Peking University, Beijing 100871, P. R. China.
Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Renal Division, Peking University First Hospital; Peking University Institute of Nephrology, Beijing 100034, P. R. China.
ACS Sens. 2023 Apr 28;8(4):1710-1722. doi: 10.1021/acssensors.2c02863. Epub 2023 Mar 29.
An intelligent closed-loop system that senses glucose and automatically delivers insulin can provide enhanced glycemic control for diabetes management. Here, we report for the first time on the development of a wearable, sensing-controlled, ultrasound-based closed-loop microneedle smart system for diabetes management. Polylactic acid (PLA) hollow microneedles were fabricated by soft lithography that can maintain excellent mechanical strength and stability in biofluids, followed by the deposition of sensing electrodes on the outer layer. An ultrasonic insulin pump was constructed by integrating a lead zirconate titanate piezoelectric (PZT) ring and a biocompatible stainless-steel sheet with hundreds of tapered holes on top of the inner layer of the microneedles. Both the sensor and the pump were powered and controlled by a printed circuit board (PCB). When the sensing device detects interstitial glucose levels above normal, the closed-loop control algorithm triggers the ultrasonic pump to deliver insulin into the interstitial fluid through the microneedle hollow channels of the PLA microneedles. The ultrasound from the pump can cause the vaporization of insulin in the subcutaneous tissue fluid, accelerate the diffusion rate, and improve the efficiency of insulin treatment and utilization. The system has successfully demonstrated effective control of glucose levels in diabetic rats. The glucose sensor showed a high sensitivity of 0.212 μA/mM at 0-28 mM with a detection limit of 14 μM, and the mean absolute relative difference (MARD) was 9.96% with an average error of 1.6 mM. The flow rate of the ultrasonic pump was 120 μL/min, and the glucose-lowering rate was 4 mM/h. This work may open a new paradigm for the development of intelligent systems for diabetes management, as well as a wide range of practical applications in diabetes patients.
一种能够感知葡萄糖并自动输送胰岛素的智能闭环系统可为糖尿病管理提供更好的血糖控制。在此，我们首次报告了一种用于糖尿病管理的可穿戴、传感控制、基于超声的闭环微针智能系统的研发情况。聚乳酸（PLA）空心微针通过软光刻技术制造，其在生物流体中能保持出色的机械强度和稳定性，随后在外层沉积传感电极。通过将锆钛酸铅压电（PZT）环和顶部带有数百个锥形孔的生物相容性不锈钢片集成到微针内层顶部，构建了一个超声胰岛素泵。传感器和泵均由印刷电路板（PCB）供电和控制。当传感装置检测到组织间液葡萄糖水平高于正常时，闭环控制算法会触发超声泵通过PLA微针的微针空心通道将胰岛素输送到组织间液中。泵发出的超声可使皮下组织液中的胰岛素汽化，加快扩散速率，提高胰岛素治疗和利用效率。该系统已成功证明对糖尿病大鼠的血糖水平有有效控制作用。葡萄糖传感器在0至28 mM范围内灵敏度高达0.212 μA/mM，检测限为14 μM，平均绝对相对差异（MARD）为9.96%，平均误差为1.6 mM。超声泵的流速为120 μL/min，降糖速率为4 mM/h。这项工作可能为糖尿病管理智能系统的开发开创一个新范式，以及在糖尿病患者中广泛的实际应用。
