Minimally invasive technique for measuring transdermal glucose with a fluorescent biosensor

• Published in: Analytical and bioanalytical chemistry 2018-11, Vol.410 (27), p.7249-7260
• Main Authors: Brown, Sheniqua, Zambrana, Paige N., Ge, Xudong, Bagdure, Dayanand, Stinchcomb, Audra L., Rao, Govind, Tolosa, Leah
• Format: Article
• Language: English
• Subjects: Adult; Analytical Chemistry; Animal models; Animals; Biochemistry; Biosensing Techniques - instrumentation; Biosensors; Blood Glucose - analysis; Blood Glucose Self-Monitoring - instrumentation; Blood glucose tests; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Diffusion; E coli; Equipment and supplies; Equipment Design; Escherichia coli - chemistry; Escherichia coli Proteins - chemistry; Fluorescent Dyes - chemistry; Fluorescent indicators; Food Science; Glucose; Glucose monitoring; Humans; Irritation; Laboratory Medicine; Medical research; Medical technology; Methods; Monitoring/Environmental Analysis; Needles; Pediatrics; Permeability; Portable equipment; Proteins; Reproducibility of Results; Research Paper; Sensitivity analysis; Skin; Skin - blood supply; Swine; Swine, Miniature; Tagging
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-018-1336-8

There is a need for blood glucose monitoring techniques that eliminate the painful and invasive nature of current methods, while maintaining the reliability and accuracy of established medical technology. This research aims to ultimately address these shortcomings in critically ill pediatric patients. Presented in this work is an alternative, minimally invasive technique that uses microneedles (MN) for the collection of transdermal glucose (TG). Due to their comparable skin properties, diffusion studies were performed on full thickness Yucatan miniature pig skin mounted to an in-line diffusion flow cell and on different skin sites of human subjects. Collected TG samples were measured with a L255C mutant of the E. coli glucose-binding protein (GBP) with an attached fluorescent probe. The binding constant ( K d  = 0.67 μM) revealed the micromolar sensitivity and high selectivity of the his-tagged GBP biosensor for glucose, making it suitable for TG measurements. In both the animal and human models, skin permeability and TG diffusion across the skin increased with MN application. For intact and MN-treated human skin, a significant positive linear correlation ( r  > 0.95, p