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Cited by 30Photonic Crystals and ApplicationsPolydiacetylene-based materials and applicationsAnalytical Chemistry and Sensors

Noninvasive Photonic-Crystal Material for Sensing Glucose in Tears

Khalil, Omar S·2004·Clinical Chemistry
DOI 10.1373/clinchem.2004.042978
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Abstract

Most noninvasive (NI) methods for the determination of glucose either detect a small specific glucose signal or measure the effect of glucose on a tissue optical property (1)(2). A recent review identified the three main issues in NI glucose measurements as specificity, compartmentalization of glucose values, and calibration (1). This editorial discusses a photonic crystal method (3), with respect to these issues. Asher’s group have constructed a photonic glucose sensor in the form of thin acrylamide PCCA hydrogel films that contain glucose molecular recognition elements (3)(6)(7). Phenylboronic acid derivatives in the lattice bind glucose, causing a change in charge distribution and a blue shift, −Δλ, in the diffracted light (3). In vitro experiments showed that Δλ responded to changes in glucose concentration with highest sensitivity at glucose concentrations <10 mmol/L (3)(6)(7). The magnitude of the blue shift decreased as a function of glucose concentration when glucose approached 20 mmol/L (3). This made the PCCAs suitable only for detection of the tear-glucose concentration, which is considerably lower than that of blood. The PCCA lattice shrinks as the glucose concentration increases (3) and possibly reaches a lower limit where minimal Δλ is observed. The authors conceive using the polymer film sensor as a contact lens that changes color according to the glucose concentration in tears. Boronic acid fluorophores embedded in a commercial contact lens and immersed in glucose solutions undergo changes in fluorescence intensity and wavelength on binding to glucose (8). The fluorescent contact lens film has the highest sensitivity at low glucose concentrations, which correspond to those in tear fluid. The novelty and the sensitivity of PCCAs at low glucose concentrations are the impetus for this editorial, in which I examine the contact lens construct as a NI glucose testing modality. The detection method depends on interaction between glucose and a specific binding molecule. It will have a specificity advantage over near-infrared absorption and scattering methods, but successful application in vivo is awaited. The dynamic range is limited to the glucose concentration in tears (3). The reversibility of the Δλ change on a reverse in the change in glucose concentration must be demonstrated in animal models and in human volunteers. Current patient care is based on measurement of glucose in venous blood or arterialized venous blood. NI methods attempt to determine glucose in other body fluids, such as in tissue interstitial fluid, eye vitreous fluid, or tears, as substitutes for venous or capillary blood glucose. NI-determined glucose values in any body compartment must track changes in blood glucose without a lag time (9). This may not be the case when changes in blood glucose concentrations are sudden and are of too large a magnitude to allow for equilibration between the vascular compartment and other body compartments (1)(9)(10). Even for blood glucose measurements, there are site-specific rates of increase and decrease in blood glucose values (10). Equilibration between glucose in the blood and in other body fluids is a controversial issue with widely different reported lag times (1). Alexeev et al. (3) propose using photonic contact lens sensors with tears as the body fluid. The relative concentrations and lag times between glucose concentrations in tears and in the vascular system will require detailed studies. Tears are generated in the lachrymal glands, and external stimuli affect the rate of tear generation. There are limited reports on the relationship between tear and blood glucose concentrations. The relationship seems to depend on the sampling method for tears and the extent of eye irritation during sampling (11). Earlier tear-glucose studies were semiquantitative because the investigators used color strips, and they did not include glucose surge experiments. Gassett et al. (12) showed that in an oral glucose tolerance test (OGTT), tear-glucose concentrations tracked blood glucose with a time lag (from graph) of ∼20 min. The mean (SD) tear glucose value for 30 nondiabetic individuals was 0.24 (0.17) mmol/L, and that of blood was 4.4 (1.7) mmol/L (12). Citing earlier studies, Van Haeringen (11) concluded that there was no significant increase in tear-glucose concentrations when blood glucose concentrations were >20 mmol/L, which he considered to indicate that the corneal and conjunctival epithelium acted as a barrier against glucose transfer from tissues into the tear fluid. Tissue fluid, and not the lachrymal gland fluid, contributed to the “tear glucose” after mechanically stimulated methods of collection, making the relationship between tear glucose and blood glucose concentrations similar to that between blood glucose and tissue fluid (11). Daum and Hill (13) reported a mean tear-glucose concentration of 0.42 (0.36) mmol/L for 12 nondiabetic individuals. The tear-glucose concentration general

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  • Other contact lens-based optical sensors have involved the use of photonic crystal materials in combination with responsive hydrogels or fluorescent dyes for measuring glucose and other target analytes in tears.

    “Other contact lens-based optical sensors have involved the use of photonic crystal materials in combination with responsive hydrogels or fluorescent dyes for measuring glucose and other target analytes in tears110-113.”

    From Wearable biosensors for healthcare monitoring (2019) · cites this paper as [110]

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  1. Heinemann L, Koschinsky T. Continuous glucose monitoring: an overview of today's technologies and their clinical applications [Review]. Int J Clin Pract Suppl 2002;129:75-9.

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Authors
Khalil, O. S.
Affiliations
Abbott (United States) (US)
Corresponding author
Khalil, Omar S
Venue
Clinical Chemistry
Publisher
Oxford University Press (OUP)
Published
2004-12-01
Volume
50
Issue
12
Pages
2236-2237
ISSN
  • 0009-9147 (ISSN-L)
  • 1530-8561
DOI
10.1373/clinchem.2004.042978
OpenAlex
W2121778355
Cited by
30
References
13
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2012: 2
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Clinical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Photonic Crystals and Applications
  • Physical Sciences › Chemistry › Organic Chemistry › Polydiacetylene-based materials and applications
  • Physical Sciences › Chemical Engineering › Bioengineering › Analytical Chemistry and Sensors
Keywords
non-invasive glucose monitoring, photonic crystals, tear glucose, phenylboronic acid, blue shift, calibration, dynamic range, blood glucose monitoring, diabetes monitoring, sensor reversibility
MeSH terms
Blood Glucose, Boronic Acids, Contact Lenses, Crystallization, Glucose, Humans, Microspheres, Tears

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