Over the past decade, the diabetes community has benefited enormously from the successful commercialization of multiple generations of continuous glucose monitors (CGMs). These devices are able to report readings of glucose in the interstitial fluid (ISF) to users on a near real-time basis. Over the few years, driven primarily by demands for improved glycemic management in insulin-dependent diabetes, the accuracy and reliability of CGM devices made further advances leading to FDA approval of their use in determining insulin dosing without the need for confirmatory fingersticks. The latest generation of CGM devices are routinely used to provide input to automated insulin delivery (AID) systems. However, despite these impressive improvements in CGM technology, CGMs today remain limited to the measurement of a single analyte and lack the ability to take redundant measurements. It is increasingly recognized that further advances in glycemic management will likely require the addition of other circulating biomarkers to elucidate individual variability in glycemic response, especially to physical activity. Measurement of freely circulating lactate can augment established glucose measurements as lactate has been found to shift glycemic thresholds for hypoglycemia in individuals with T1D to lower plasma glucose concentrations [33]. This project thus aims to provide a novel CGM platform capable of accurately measuring both glucose and lactate. We believe that a combined glucose and lactate continuous monitoring system will enhance the safety and efficacy of the next generation of AID systems. Biolinq has developed a body-worn patch containing a microneedle array with multiplexed sensing elements. Clinical studies to date have used a microneedle array consisting of individually-addressable microneedles inserted into the reticular dermis - approximately 200 to 350 microns below the surface of the skin. Previous work has shown a high level of correlation between glucose in the dermal interstitial fluid and blood glucose [57]. Our clinical studies have confirmed the high level of correlation reported and low lag time previously established for glucose in the dermal ISF [36]; we believe this is a unique property of sensing in the dermis and can be extended to other metabolites. In accordance with the project plan, the research effort seeks to attain the following objectives: (1) development and refinement of a lactate-selective sensing chemistry and its co-location with Biolinq's clinically-validated glucose-selective chemistry, (2) implementation of redundant measures of glucose and lactate in a microneedle array sensor platform featuring individually-addressable sensing elements to provide accurate and reliable measurements in the dermal ISF, and (3) design of an end-to-end body-worn sensing system containing a miniaturized, low-power application-specific integrated circuit with Bluetooth wireless capability. The technology and business objectives outlined in this proposal will have a direct impact on open- and closed-loop insulin delivery and should meet current needs for an accurate, non-invasive continuous glucose and lactate monitor with broad applicability owing to its enhanced reliability, accuracy, simple use profile, and low-cost nature.
Public Health Relevance Statement: "A hybrid continuous glucose and lactate monitor with improved signal reliability" Biolinq Inc. (f/k/a Electrozyme LLC) 8. PROJECT NARRATIVE The proposed project aims to develop a microneedle array-based intradermal biosensor for the continuous assessment of glucose and lactate levels in the dermal interstitial fluid. This new multi-variate biosensor paradigm will impart the ability to perform non-invasive, pain-free sensing in a redundant fashion with a low level of latency, thereby providing insight into glycemic variability during rapid rates of change, especially during instances of hypoglycemia and bouts of physical activity. The development activity will thus lead to the validation of a unique wearable multi-variate sensing platform with enhanced accuracy and reduced patient burden, which will augment the safety and effectiveness of CGM and its integration into open and closed loop hormone replacement systems for diabetes management.
Project Terms: Archives; Blood Glucose; Blood Sugar; Buffers; Chemistry; Clinical Research; Clinical Study; Communities; Data Display; Dermis; Corium; Cutis; Diabetes Mellitus; diabetes; Insulin-Dependent Diabetes Mellitus; Brittle Diabetes Mellitus; IDDM; Juvenile-Onset Diabetes Mellitus; Ketosis-Prone Diabetes Mellitus; Sudden-Onset Diabetes Mellitus; T1 DM; T1 diabetes; T1D; T1DM; Type 1 Diabetes Mellitus; Type 1 diabetes; Type I Diabetes Mellitus; insulin dependent diabetes; juvenile diabetes; juvenile diabetes mellitus; ketosis prone diabetes; type I diabetes; type one diabetes; Elements; Glucose; D-Glucose; Dextrose; Hormones; Endocrine Gland Secretion; Therapeutic Hormone; Hybrids; Hypoglycemia; hypoglycemic; hypoglycemic episodes; In Vitro; Insulin; Humulin R; Novolin R; Regular Insulin; Lead; Pb element; heavy metal Pb; heavy metal lead; Noise; Patients; Reading; Research; Safety; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Technology; Time; Transducers; Translating; Work; Generations; Measures; Businesses; Custom; Intercellular Fluid; Interstitial Fluids; base; sensor; improved; Surface; Clinical; Phase; Physiological; Physiologic; Ensure; Evaluation; Physical activity; Dermal; insight; Individual; Databases; Data Bases; data base; Oxidases; Measurement; Nature; Life; Pulse; Physiologic pulse; Hour; Dimensions; System; Location; Height; biocompatibility; biomaterial compatibility; monitoring device; Performance; biological sensor; Biosensor; sterile; Sterility; novel; Devices; Reporting; Sampling; Property; response; glucometer; glucose meter; glucose monitor; miniaturize; Pain-Free; Phosphate Buffer; Malus domestica; Apple; Skin; Effectiveness; Diameter; Caliber; Dose; Detection; Glucose Plasma Concentration; Resolution; Validation; Wireless Technology; wireless; Monitor; Characteristics; Development; developmental; cost; design; designing; next generation; diabetes management; diabetic management; commercialization; Sterilization; Secure; Systems Development; mobile application; mobile app; mobile device application; cloud based; rate of change; circulating biomarkers; circulating markers; Bluetooth; individual variation; individual heterogeneity; individual variability; detection limit
