Feasibility of Interstitial Fluid Ketone Monitoring with Microneedles

Abstract

Diabetic ketoacidosis (DKA) is one of the most dangerous and costly complications of diabetes, accounting for approximately 50% of deaths in diabetic individuals under 24 years. This results in over 130,000 hospital admissions yearly and costs the USA over USD 2.4 billion annually. Earlier diagnosis, treatment, and management of DKA are of critical importance to achieving better patient outcomes and preventing prolonged hospital admissions. Diabetic patients undergoing stress from illness or injury may not recognize early ketosis and often present advanced ketoacidosis, requiring intensive care admission. We have recently developed a microneedle-based technology to extract dermal interstitial fluid (ISF) from both animals and humans, which could enable wearable sensors to rapidly detect ketosis. Metabolite concentrations in ISF may differ in urine and blood and could likely represent local metabolic conditions in the surrounding tissue. Development of a wearable ketone detector will require an understanding of ketone concentrations and kinetics in ISF. Here, we report data that is first of its kind, with regard to the ketone concentrations present in the dermal ISF of rats, their correlation to blood, and the possible impact on the development of a wearable ISF “early warning system” to prevent morbidity from DKA. We extracted ISF, using minimally invasive microneedle arrays, from control Sprague Dawley rats and 17 h fasted rats. ISF and blood ketone levels were measured using a common glucose/ketone meter and strips. Local tissue concentrations of glucose were similar to those of blood, with an average blood to ISF glucose ratio of 0.99 ± 0.15 mg/dL. ISF ketones (0.4 ± 0.3 mM) were significantly higher (p = 4.2 × 10−9), compared with blood ketones (0.0 ± 0.0 mM). Although the fasted animals had slightly higher ISF ketones (1.3 ± 1.1 mM) compared with blood ketones (1.0 ± 1.0 mM), the difference was not significant (p = 0.3). This suggests ISF could possibly be useful as a surrogate for blood when determining ketone levels within a clinical setting.

Update on Measuring Ketones

“…72 Another method under development would be with a microneedle sampling method with a sensor array, which could measure interstitial fluid ketone levels and potentially also measure other analytes, such as glucose and lactate. 73,74 As ketone concentrations in blood and interstitial fluid are normally low, a factory calibration feature for non-adjunctive use will greatly increase the adoption of these products. A combined CGM and CKM could be incorporated into AID systems and provide alarms and additional safety measures related to these two analytes.…”

“…75 A CKM may help identify rising ketone levels and allow people with impeding euglycemic DKA to take corrective action, such as hydration and insulin treatment, with or without carbohydrate intake, to prevent ketoacidosis. 75 -77 For SGLT2i users with diabetes, ketone measurements are indicated for symptoms suggesting DKA, such as malaise, fatigue, nausea, or vomiting. These SGLT2i users should also measure ketones in a setting of infection, dehydration, injury, or an insulin pump malfunction.…”

Advancements in Airborne Viral Nucleic Acid Detection with Wearable Devices

“…This is true, more generally, of wearable sensors that report on the presence of a target analyte in complex fluids such as air, sweat, or interstitial fluid. [2,21,[34][35][36][37] The goal of the first stage is to collect enough of the target analyte, in this case, viral RNA or DNA, for detection by the chosen analyte sensing method. Current nucleic acid detection methods require the nucleic acids to be suspended in a liquid buffer.…”

Wearable Vertical Graphene-Based Microneedle Biosensor for Real-Time Ketogenic Diet Management

“…24 While several studies have illustrated the feasibility of using microneedles to monitor interstitial ketone levels, most have only demonstrated in vitro studies without any on-body investigations. 25,26 So far, electrochemical sensors are widely used in biomarker monitoring and detection due to their high sensitivity, low cost, and ease of use advantages. 27 In such sensors, the electrochemical transduction performance largely depends on the material properties of the sensing element.…”

“…Of these methods, microneedle arrays provide a pain-free way to access ISF directly . While several studies have illustrated the feasibility of using microneedles to monitor interstitial ketone levels, most have only demonstrated in vitro studies without any on-body investigations. , …”