Towards reagent-free blood glucose monitoring using micro-dialysis and infrared transmission spectrometry

Micro-dialysis is commonly used as a minimal invasive technique for continuously harvesting body fluids with substrate and metabolite composition similar to blood. We have investigated the dialysates of 112 blood plasma samples of different patients, employing CMA 60 μ-dialysis probes with Ringer's solution as perfusate, by infrared transmission spectroscopy. Components contributing to the dialysate spectra have been identified. Partial least squares (PLS) regression of the absorbance spectra of either 4 or 16 cm−1 spectral resolution led to best standard errors of prediction (SEP) of around 2.4 mg/dl for the glucose concentrations. Slight variation in SEP was observed between calibration models based on either full interval data or after the selection of four significant spectral variables. The uncertainty budget from the reference assay and that from spectral measurements has been estimated from background spectra with the pure perfusate filled cell, enabling also an estimate of the residual variance due to non-modelled cross-sensitivities. A micro-fluidic system for μl-sample transfer from the dialysis probe to the micro-cell housed within the spectrometer sample compartment has been designed and tested for reliable long-term quasi-continuous monitoring.