# Validation of Analytical Models for the Development of Non-Invasive Glucose Measurement Devices

## TL;DR

This paper proposes a new method to measure glucose non-invasively using spectrophotometry, focusing on optimizing extinction coefficients and addressing non-linear behavior in biological samples.

## Contribution

The paper introduces a validated methodology for determining glucose's extinction coefficient in blood, accounting for molecular interactions and non-linear optical behavior.

## Key findings

- Glucose shows high spectral sensitivity near 975 nm, with extinction coefficients ranging from −0.0045 to −0.0053.
- A regression model successfully differentiates glucose and insulin concentrations using absorbance at 965, 975, and 985 nm.
- The proposed model aligns with mid-infrared validation studies, confirming its relevance for glucose monitoring in biological media.

## Abstract

Non-invasive glucose monitoring remains a persistent challenge in the scientific literature due to the complexity of biological samples and the limitations of traditional optical methods. Although advances have been made in the use of near-infrared (NIR) spectrophotometry, the direct application of the Lambert–Beer Law (LBL) to such systems has proven problematic, particularly due to the non-linear behavior observed in complex organic solutions. In this context, the objective of this work is to propose and validate a methodology for the determination of the extinction coefficient of glucose in blood, taking into account the limitations of the LBL and the specificities of molecular interactions. The method was optimized through an iterative process to provide consistent results over multiple replicates. Whole blood and plasma samples from two individuals were analyzed using spectrophotometry in the 700 nm to 1400 nm. The results showed that glucose has a high spectral sensitivity close to 975 nm.The extinction coefficients obtained for glucose (αg) ranged from −0.0045 to −0.0053, and for insulin (αi) from 0.000075 to 0.000078, with small inter-individual variations, indicating strong stability of these parameters. The non-linear behaviour observed in the relationship between absorbance, glucose and insulin concentrations might be explained by the changes imposed by both s and p orbitals of organic molecules. In order to make the LBL valid in this context, the extinction coefficients must be functions of the analyte concentrations, and the insulin concentration must also be a function of glucose. A regression model was found which allows to differentiate glucose from insulin concentration, by considering the cuvette thickness and sample absorbance at 965, 975, and 985 nm. It can also be concluded from experiments that wavelength of approximately 975 nm is more suitable for blood glucose calculation by using photometry. The final spectra are consistent with those reported in mid-infrared validation studies, suggesting that the proposed model encompasses the key aspects of glucose behavior in biological media.