Abstract
We present the first demonstration of glycated albumin detection and quantification using Raman spectroscopy without the addition of reagents. Glycated albumin is an important marker for monitoring the long-term glycemic history of diabetics, especially as its concentrations, in contrast to glycated hemoglobin levels, are unaffected by changes in erythrocyte life times. Clinically, glycated albumin concentrations show a strong correlation with the development of serious diabetes complications including nephropathy and retinopathy. In this article, we propose and evaluate the efficacy of Raman spectroscopy for determination of this important analyte. By utilizing the pre-concentration obtained through drop-coating deposition, we show that glycation of albumin leads to subtle, but consistent, changes in vibrational features, which with the help of multivariate classification techniques can be used to discriminate glycated albumin from the unglycated variant with 100% accuracy. Moreover, we demonstrate that the calibration model developed on the glycated albumin spectral dataset shows high predictive power, even at substantially lower concentrations than those typically encountered in clinical practice. In fact, the limit of detection for glycated albumin measurements is calculated to be approximately four times lower than its minimum physiological concentration. Importantly, in relation to the existing detection methods for glycated albumin, the proposed method is also completely reagent-free, requires barely any sample preparation and has the potential for simultaneous determination of glycated hemoglobin levels as well. Given these key advantages, we believe that the proposed approach can provide a uniquely powerful tool for quantification of glycation status of proteins in biopharmaceutical development as well as for glycemic marker determination in routine clinical diagnostics in the future.
Highlights
Glucose forms the most ubiquitous energy source in biology
Significant improvements to the current results can be made, especially through optimization of instrumentation and via enhanced chemometric modeling. This proof-of-concept study represents the first use of Raman spectroscopy, without application of extraneous reagents, to detect and quantify the concentration of glycated albumin, an important glycemic marker for long-term diabetes monitoring
We have demonstrated that application of drop-coating deposition Raman spectroscopy can accurately discriminate glycated albumin from the unglycated variant, even at low mM concentrations
Summary
Glucose forms the most ubiquitous energy source in biology. In humans, glucose is primarily derived from the breakdown of carbohydrates in the diet or in body stores (glycogen), in addition to secondary endogenous synthesis from protein or from the glycerol moiety of triglycerides [1]. Even under diverse conditions (such as feeding, fasting and severe exercise), the blood glucose level is maintained within a fairly narrow interval, 70–120 mg/dL, by the homeostatic system of a healthy individual. This implies that, for an average person, the total quantity of glucose in the blood and body fluids is approximately 5 grams - a remarkably small number given the typical carbohydrate intake per day In order to reduce/eliminate the painful and invasive nature of these fingerprick measurements, minimally invasive [4,5,6,7] and non-invasive glucose monitoring has been actively pursued by a number of research laboratories [8,9,10] including our own [11,12,13,14]
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