In vitro measurements of physiological glucose concentrations in biological fluids using mid-infrared light

Abstract

Mid-infrared transmission spectroscopy using broadband mid-infrared or Quantum Cascade laser sources is used to predict glucose concentrations of aqueous and serum solutions containing physiologically relevant amounts of glucose (50-400 mg/dL). We employ partial least squares regression to generate a calibration model using a subset of the spectra taken and to predict concentrations from new spectra. Clinically accurate measurements with respect to a Clarke error grid were made for concentrations as low as 30 mg/dL, regardless of background solvent. These results are an important and encouraging step in the work towards developing a noninvasive in vivo glucose sensor in the mid-infrared.

Keywords: (170.1470) Blood or tissue constituent monitoring; (300.1030) Absorption; (300.6340) Spectroscopy, infrared.

Fig. 1

a) Representative transmission spectra of aqueous glucose at concentrations from 10 – 10,000 mg/dL measured by FTIR spectroscopy. b-d) Prediction of glucose concentrations using calibrations ranging from 1 through 10,000 mg/dL in water (b), serum (c), and Intralipid (d). The red lines and corresponding fitting equations show changes to the linear fit when only concentrations between 1 and 100 mg/dL are used for calibration and prediction.

Fig. 2

Predicted glucose concentrations versus expected (actual) concentrations plotted on Clarke error grids [11]. Top row: aqueous solution (left) and serum solution (right) measured with FTIR. Bottom row: aqueous solution (left) and serum solution (right) measured with QC laser spectroscopy. The individual regions labeled A-E are described as follows: A - clinically accurate reading, B - result that would lead to benign action or inaction, C - results that would lead to unnecessary corrections, D - results that would lead to inaction when action is necessary, and E - results that would lead to treatment opposite to what should be given.

Fig. 3

First loading vectors for calibration sets in serum (left) and water (right), for FTIR (top row) and QC laser (bottom row) spectra, with arrows denoting wavenumber regions of the most prominent absorption features.