Increased in vivo stability and functional lifetime of an implantable glucose sensor through platinum catalysis

Abstract

Understanding and improving in vivo materials related to signal stability and preservation for active chemical sensor and biosensor transduction systems is critical in achieving implantable medical sensors for long-term in vivo applications. During human in vivo clinical testing of an implantable glucose sensor based on a glucose sensitive hydrogel, post-explant analysis showed that the boronate recognition element had been oxidized from the fluorescent indicator, causing a rapid loss of signal within hours after implant. Additional wet-bench analytical evidence and reproduction in vitro suggests reactive oxygen species, particularly hydrogen peroxide (H2O2), stemming from natural inflammatory response to the material, to be the cause of the observed oxidative de-boronation. A 3-nm thick deposition of metallic platinum (Pt) placed by plasma sputtering onto the porous surface of the hydrogel, showed immediate protection from sensor signal loss due to oxidation both in vitro and in vivo, greatly extending the useful lifetime of the implantable glucose sensor from 1 day to an expected ≥6 months. This finding may represent a new strategy to protect an implanted material and/or device from in vivo oxidative damage, leading to much improved overall stability and reliability for long-term applications.

Clinical Results of an Automated Artificial Pancreas Using Technosphere Inhaled Insulin to Mimic First-Phase Insulin Secretion

“…35,36 In patients with type 1 diabetes using insulin glargine, a randomized trial showed that prandial TI led to significantly lower fasting and 1-and 2-hour postprandial glucose values compared to prandial insulin lispro, with a lower hypoglycemia event rate. 37 Several other published clinical studies have further supported TI's safety and efficacy as a prandial insulin in type 1 diabetes 29,38,39 and type 2 diabetes. 29,40,41 At the time of the study TI was an investigational drug that was approved on June 27, 2014, as an ultra rapid-acting insulin for oral inhalation indicated for the treatment of adults with type 1 or type 2 diabetes mellitus in the US by the food and drug administration.…”

Multisite Study of an Implanted Continuous Glucose Sensor Over 90 Days in Patients With Diabetes Mellitus

“…26 By contrast, the Senseonics CGM sensor detects glucose via a nonenzymatic, abiotic methodology that is not subject to degradation or to the stability limitations inherent to enzyme-based systems. 18 In addition, transcutaneous sensors of other CGMs protrude from the skin and do not allow for resolution of an acute inflammatory response, thereby limiting sensor accuracy and performance. The Senseonics sensor is fully inserted into the interstitial tissue, thus allowing the body to heal the insertion wound and resolve the acute inflammatory response.…”

“…Ex vivo chemical analysis performed after sensor removal showed loss of fluorescence due to chemical degradation of the indicator moieties, the mechanism of which has been previously described. 18 The daily calibration points enable the system to account for this loss of fluorescence in vivo with a real-time assessment of the indicators sensitivity to glucose variations. This assessment enables updates to the fluorescent baseline and the responsiveness corresponding to the chemical kinetics for the degradation mechanisms.…”

Nanomedicine and Nanotechnology for Medicine

“…It is then detected by an amperometric biosensor. From [5] While ultra-miniaturisation combined with surface functionalisation with selected molecules can lead to biocompatible devices, the issues of energy autonomy, selfdiagnosis, remote control, and data transmission remain considerable challenges for the implementation of such systems.…”