A Fully Integrated Closed‐Loop System Based on Mesoporous Microneedles‐Iontophoresis for Diabetes Treatment

Abstract

A closed‐loop system that can mini‐invasively track blood glucose and intelligently treat diabetes is in great demand for modern medicine, yet it remains challenging to realize. Microneedles technologies have recently emerged as powerful tools for transdermal applications with inherent painlessness and biosafety. In this work, for the first time to the authors' knowledge, a fully integrated wearable closed‐loop system (IWCS) based on mini‐invasive microneedle platform is developed for in situ diabetic sensing and treatment. The IWCS consists of three connected modules: 1) a mesoporous microneedle‐reverse iontophoretic glucose sensor; 2) a flexible printed circuit board as integrated and control; and 3) a microneedle‐iontophoretic insulin delivery component. As the key component, mesoporous microneedles enable the painless penetration of stratum corneum, implementing subcutaneous substance exchange. The coupling with iontophoresis significantly enhances glucose extraction and insulin delivery and enables electrical control. This IWCS is demonstrated to accurately monitor glucose fluctuations, and responsively deliver insulin to regulate hyperglycemia in diabetic rat model. The painless microneedles and wearable design endows this IWCS as a highly promising platform to improve the therapies of diabetic patients.

Minimally invasive technology for continuous glucose monitoring

“…Li et al presented an integrated closed-loop system based on mesoporous MN array for diabetes diagnosis and treatment [32]. As the main component of this system, the glucose sensor consists of a mesoporous MN array, a planar glucose electrode, a reverse iontophoresis extraction component and a 3D-printed sensing chamber.…”

Recent Progress in Intelligent Wearable Sensors for Health Monitoring and Wound Healing Based on Biofluids

“…(L) An ionic bioelectronic skin patch for monitoring of temperature, pressure, pH, and electrocardiogram data (Shi and Wu, 2021). 2017; Mishra et al, 2018;Choi et al, 2019), small molecules (Munje et al, 2017;Parlak et al, 2018;Li et al, 2021), biochemical factors (Mak et al, 2015), and environmental signals (Pal et al, 2020;Liu et al, 2021;Shi and Wu, 2021). This section systematically summarizes the latest applications of intelligent wearable sensors for monitoring biomarkers in various biofluids (Figure 1) as summarized in Table 2.…”

“…in vitro and in vivo for health monitoring ( Sturgeon et al, 2008 ; Jia et al, 2012 ; Gromov et al, 2013 ; Broza et al, 2015 ; Heikenfeld et al, 2019 ; Shrivastava et al, 2020 ). These biomarkers include physiological metabolites ( Han et al, 2017 ; Tur-Garcia et al, 2017 ; Mishra et al, 2018 ; Choi et al, 2019 ), small molecules ( Munje et al, 2017 ; Parlak et al, 2018 ; Li et al, 2021 ), biochemical factors ( Mak et al, 2015 ), and environmental signals ( Pal et al, 2020 ; Liu et al, 2021 ; Shi and Wu, 2021 ). This section systematically summarizes the latest applications of intelligent wearable sensors for monitoring biomarkers in various biofluids ( Figure 1 ) as summarized in Table 2 .…”

“…Dervisevic et al reported a type of high-density silicon microneedle array patch for in-situ monitoring of blood in ISF ( Dervisevic et al, 2021 ). Another study proposed an integrated wearable closed-loop system based on mesoporous microneedle iontophoresis with a diabetes treatment system ( Li et al, 2021 ). In addition to the minimally invasive extraction of ISF in the form of microneedles mentioned above, ISF can also be extracted to the skin’s surface by reverse iontophoresis or ultrasonic introduction ( Leboulanger et al, 2004 ; Yu et al, 2012 ).…”

Sequential and Comprehensive Algorithm for Fault Detection in Semiconductor Sensors

“…Biomedical microelectromechanical system (BioMEMS) is one of the representative areas that has progressed with the development of the semiconductor industry. Various biochips have previously been developed using the semiconductor fabrication process [7][8][9]. The front-end fabrication process of the semiconductor silicon chips was classified into seven main processes: photolithography, etching, deposition, chemical mechanical planarization, oxidation, ion implantation, and diffusion, as previously described [10].…”