Continuous Ketone Monitoring: A New Paradigm for Physiologic Monitoring

In this issue of JDST, Alva and colleagues present for the first time, development of a continuous ketone monitor (CKM) tested both in vitro and in humans. Their sensor measured betahydroxybutyrate (BHB) in interstitial fluid (ISF). The sensor was based on wired enzyme electrochemistry technology using BHB dehydrogenase. The sensor required only a single retrospective calibration without a need for further adjustments over 14 days. The device produced a linear response over the 0-8 mM range with good accuracy. This novel CKM could provide a new dimension of useful automatically collected information for managing diabetes. Passively collected ISF ketone information would be useful for predicting and managing ketoacidosis in patients with type 1 diabetes, as well as other states of abnormal ketonemia. Although additional studies of this CKM will be required to assess performance in intended patient populations and prospective factory calibration will be required to support real time measurements, this novel monitor has the potential to greatly improve outcomes for people with diabetes. In the future, a CKM might be integrated with a continuous glucose monitor in the same sensor platform.

Feasibility of Continuous Ketone Monitoring in Subcutaneous Tissue using a Ketone Sensor

Background: The feasibility of measuring β-hydroxybutyrate in ISF using a continuous ketone monitoring (CKM) sensor using a single calibration without further adjustments over 14 days is described. Methods: A CKM sensor was developed using wired enzyme technology with β-hydroxybutyrate dehydrogenase chemistry. In vitro characterization of the sensor was performed in phosphate buffered saline at 37°C. In vivo performance was evaluated in 12 healthy participants on low carbohydrate diets, who wore 3 ketone sensors on the back of their upper arms to continuously measure ketone levels over 14 days. Reference capillary ketone measurements were performed using Precision Xtra® test strips at least 8 times a day. Results: The sensor is stable over 14 days and has a linear response over the 0-8 mM range. The operational stability of the sensor is very good with a 2.1% signal change over 14 days. The first human study of the CKM sensor demonstrated that the sensor can continuously track ketones well through the entire 14 days of wear. The performance with a single retrospective calibration of the sensor showed 82.4% of data pairs within 0.225 mM/20% and 91.4% within 0.3 mM/30% of the capillary ketone reference (presented as mM at <1.5 mM and as percentage at or above 1.5 mM). This suggests that the sensor can be used with a single calibration for the 14 days of use. Conclusions: Measuring ketones in ISF using a continuous ketone sensor is feasible. Additional studies are required to evaluate the performance in intended patient populations, including conditions of ketosis and diabetic ketoacidosis.

Direct visible light activation of a surface cysteine-engineered [NiFe]-hydrogenase by silver nanoclusters

Engineering a cysteine close to the distal [4Fe–4S] cluster of a [NiFe]-hydrogenase creates a specific target for Ag nanoclusters, the resulting ‘hard-wired’ enzyme catalyzing rapid hydrogen evolution by visible light.

Glucose Biosensor Based on Immobilization of Glucose Oxidase on Silica Nanoparticles Modified Au Electrode

A feasible method to fabricate glucose biosensor was developed by covalent attachment of glucose oxidase (GOx) to a silica nanoparticle monolayer modified gold electrode. Electrochemical impedance spectroscopy (EIS) of ferrocyanide followed the assembly process and verified the successful immobilization of GOx on silica nanoparticle modified on gold electrodes. Cyclic voltammetry (CV), performed in the presence of excess glucose and artificial redox mediator (ferrocenemethanol), allowed to quantify the surface concentration of electrically wired enzyme. The signal of proposed electrode was more than 2.5 times of that on electrode lacking silica nanoparticles. As a result, silica nanoparticles are a good biocompatible solid support for enzyme immobilization.