Wearable, Sensing-Controlled, Ultrasound-Based Microneedle Smart System for Diabetes Management.

Abstract

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.