Glucose Quantification in Dried-down Nanoliter Samples Using Mid-Infrared Attenuated Total Reflection Spectroscopy

The aim of this study was to determine the feasibility of minimally invasive glucose concentration measurement of a body fluid within the physiologically important range below 100 nL with a number of samples such as interstitial fluid, plasma, or whole blood using mid-infrared spectroscopy, but starting with preliminary measurements on samples of simple aqueous glucose solutions. The Fourier transform infrared spectrometer was equipped with a Golden Gate® single reflection diamond attenuated total reflection (ATR) accessory and a room-temperature pyroelectric detector. As the necessary detection limits can be achieved only for dried samples within the spectrometric conditions realized by a commercial instrument, the work focused on the optimization of such ATR measurements. We achieved quantification of samples with volumes as low as 7 nL between 10 and 600 mg/dL. The standard error of prediction (SEP) for the concentration range 10–100 mg/dL is 3.2 mg/dL with full interval data between 1180 and 940 cm⁻¹. The performance of the prediction is given by a coefficient of variation of prediction (CV_pred) of 6.2%. When all samples within the whole concentration range are included, the SEP increases to 20.2 mg/dL, and hence the CV_pred to 10.6% due to a nonlinear signal dependence on glucose concentration. A detection limit for glucose of 0.7 ng with a signal-to-noise ratio of 10 was obtained.