Analytical Characterization of Electrochemical Biosensor Test Strips for Measurement of Glucose in Low-Volume Interstitial Fluid Samples

Abstract

Background: Minimally invasive interstitial fluid (ISF) sampling and glucose measurement technologies were integrated into a hand-held device for diabetic glucose monitoring investigations. Methods: Conventional electrochemical test strip technology (Bayer Glucometer Elite®) was adapted to measure glucose in small (0.5–2.0 μL) samples of ISF. Test strip glucose measurements were performed on a commercial potentiostat and were compared to various reference glucose methodologies (YSI 2300 analyzer, microhexokinase procedure, Bayer Glucometer Elite). Characterizations of the integrated ISF sampling-glucose test strip design included accuracy and precision in various sample media (saline, ISF surrogates, diabetic ISF samples), sample volume dependence, test strip sterilization studies (electron beam, γ irradiation), and diabetic ISF sampling and glucose measurements. Results: Glucose measurements were free from significant media effects. Sample volume variations (0.6–3.2 μL) revealed only modest dependence of glucose measurement bias on sample volume (−1.5% per microliter). Sterilization treatments had only a minor impact on glucose response and test strip aging and no significant impact on interferent responses of the glucose test strips. Diabetic subject testing under minimum fasting conditions of at least 2 h with integrated ISF sampling and glucose measurement gave low ISF glucose measurement imprecision (CV, 4%) and mean glucose results that were indistinguishable from reference (microhexokinase) ISF glucose measurements and from capillary blood glucose measurements (Glucometer Elite). Conclusions: Conventional single-use, electrochemical glucose test strip and ISF collection technologies can be readily integrated to provide real-time ISF sampling and glucose measurements for diabetic monitoring applications.

The NEPI Antidiabetes Study (NANSY). 1: Short‐term dose–effect relations of glimepiride in subjects with impaired fasting glucose*

“…During each test week the subjects monitored blood glucose at home on one weekday and one weekend day. Blood glucose was measured before breakfast, lunch and dinner, and at bedtime, using Glucometer Elite[13] and test sticks[14]. Tests results were registered together with the subject's notes on possible hypoglycaemic symptoms.…”

A Tale of Two Compartments: Interstitial Versus Blood Glucose Monitoring

“…9 IF is a relatively passive medium that has onethird of the total protein concentration as compared to plasma with an average albumin=globulin ratio of 1.85. 15 The total body volume of the interstitial space is three times that of plasma; however, IF compartments around the cells are microscopic. 9 IF bathes the cells and feeds them with nutrients, including glucose, by providing a corridor between the capillaries and the cell.…”

Assessment of Trueness of a Glucose Monitor Using Interstitial Fluid and Whole Blood as Specimen Matrix

“…The observed increase in data dispersion and bias is in agreement with findings obtained with other cell-free matrices such as plasma (Dr. Ben Feldman, Abbott Diabetes Care, personal communication). Also, the reduced protein content of the ISF as compared with plasma or whole blood may be a source of variability and bias as indicated by Collison et al 27 While the observed bias may easily be corrected by appropriate calibration of the monitor, further investigations are necessary to properly assess the reasons for the wide dispersion of data observed with ISF as the specimen matrix.…”