Analysis of tear glucose concentration with electrospray ionization mass spectrometry

Abstract

We have developed a mass spectrometry-based method that allows one to accurately determine the glucose concentration of tear fluid. We used a 1 L micro-capillary to collect tear fluid from the tear meniscus with minimal irritation of the eye. We analyzed the 1 L volume of collected tear fluid with liquid-chromatography electrospray ionization mass spectrometry with the use of D-glucose-6,6-d 2 as an internal standard. Repeated measurements and a recovery experiment on pooled, onion-induced tears showed that the analysis of the glucose in tears was precise (4% relative standard deviation) and provided 100% recovery. We found the tear glucose concentration of one fasting nondiabetic subject to be 13 to 51 M while the onion-induced tear glucose concentration of a different nondiabetic subject to be 211 to 256 M. . Current self-monitoring methods rely on invasive finger sticks to directly measure blood glucose levels to provide the critical information required to achieve glycemic control. A number of noninvasive approaches to monitoring blood glucose concentrations are being pursued; however, none have been successfully developed to the point where they have gained widespread clinical acceptance [3]. There has been significant recent activity in exploring noninvasive monitoring by using tear fluid glucose as an indicator for blood glucose [4 -6]. Such an approach will be effective only if the glucose concentrations in tear fluid are a reliable surrogate for blood glucose concentrations.A survey of the literature over the last 70 years on tear glucose determinations indicates significant disagreement in measured tear glucose concentrations and on the relationship of tear fluid glucose to blood glucose concentrations. Daum and Hill [7] The differences in tear glucose concentrations between these reports are likely due to the use of different tear fluid collection methods. Van Haeringen and Glasius specifically addressed the dependence of tear fluid glucose on the method of collection [9]. They used a glucose dehydrogenase method to analyze chemically stimulated tears collected with a capillary and mechanically stimulated tear fluid collected by filter paper. Van Haeringen and Glasius found higher glucose concentrations in the tear fluid collected by filter paper and concluded that the increase is due to the mechanical stimulation of the corneal and conjunctival epithelium [9]. Other studies reported similar findings in experiments on rabbits [10] and in subjects who were tested immediately after swimming [7]. Therefore, it is apparent that to determine a physiologically relevant, baseline tear glucose concentration, tear fluid must be acquired with minimal tear stimulation and eye irritation.

Analysis of human tear fluid by Raman spectroscopy

“…Common collection methods include using glass capillary tubes [14], polyester rods [25], Schirmer strips [26] or eye washes [27], frequently with a form of irritation (onion vapour [28], ammonia solution [26], etc.) to increase the tear flow rate.…”

Powering electronic contact lenses: current achievements, challenges, and perspectives

“…As can be seen from FIGURE 2, the electric power obtained from glucose as a biofuel is in the microwatts range, viz., 0.02-22 mW. For an average situation, viz., basal tears with a glucose concentration close to 50 mM [24], and a tear production rate of about 3 ml/min [28], the calculated electric power is only ca. 0.3 mW.…”

“…Glucose, being the target molecule par excellence as regards the electronic lens protocols that are actively pursued, is a low-abundance substance in lachrymal fluid, that is, about 50 mM on average [24], even if values earlier reported are as high as 0.6 mM [25]. For a glucose sensing application, it would be important to mention several recent reports in the literature showing that the tear glucose concentration is quite adequately correlated (that is, real-time amounts) to blood glucose levels [5,26,27].…”

Extraction and Analysis of Inositols and Other Carbohydrates from Soybean Plant Tissues

“…As examples, Fountain and Grumbach (2009) used negative ion electrospray mass spectrometry for the analysis of fructose, glucose, sucrose, and lactose. Taormina et al (2007) and Mauri et al (2002) used flow injection techniques with mass spectrometry. Fugimoto et al (2005) used rubidium in the mobile phase as a complexing agent for both nuclear magnetic resonance and electrospray mass spectrometry analysis.…”