Cerium Oxide Nanoparticle-Containing Colorimetric Contact Lenses for Noninvasively Monitoring Human Tear Glucose

Abstract

Noninvasive methods for monitoring diabetes are being developed to eliminate the need for invasive finger-prick testing. Here, we propose the noninvasive detection of tear glucose using contact lenses that contain cerium oxide nanoparticles (CNPs). We chemically conjugated CNPs with glucose oxidase (GOx) using poly(ethylene glycol) (PEG) (CNP-PEG-GOx). GOx oxidizes glucose into hydrogen peroxide, which rapidly (∼1 min) reduces colorless Ce 3+ to yellow Ce 4+ with high sensitivity (>0.1 mM). Then, the yellow CNP-PEG-GOx can be analyzed to quantify the glucose concentration using a smartphone equipped with an image-processing algorithm. The CNP-PEG-GOx-laden contact lenses had physical properties similar to those of commercially available contact lenses and were nontoxic to human corneal cells and endothelial cells. When the CNP-PEG-GOx-laden contact lenses were placed on the eyes of diabetic rabbits, it was possible to measure the tear glucose levels. Interestingly, the lenses successfully detected glucose in human tear specimens and distinguished the diabetes status of patients. These findings suggest that the CNP-PEG-GOx-laden contact lenses could be used along with a smartphone-based image-processing algorithm to noninvasively monitor human tear glucose.

Lab‐on‐a‐Contact Lens: Recent Advances and Future Opportunities in Diagnostics and Therapeutics

“…[35] Functional nanoparticles with unique properties, such as no/low cytotoxicity, excellent physical/chemical features, and drug-delivery ability, have also been employed to improve/integrate some SCL properties. [51,62,[88][89][90] For example, it has been reported that the nanoparticles were incorporated into CL polymers and gelling systems to enhance mechanical strength and elasticity of CLs. [34] For example, organic dyeencapsulated silica nanoparticles were applied with PHEMA or PDMS to obtain precise biosensing capability, with the detection sensitivity of 0.5-5 mM of blood glucose.…”

Recent advancements in noninvasive glucose monitoring and closed-loop management systems for diabetes

“…110 Copyright 2021, Elsevier B.V. (D) CNP-PEG-GOx-laden contact lenses for colorimetric monitoring tear glucose. 111 Copyright 2021, American Chemical Society. (E) A remotely controllable smart contact lens for diabetic diagnosis and therapy.…”

“…(C) Plasmonic contact lens composed of SERS-LM for the selective glucose detection in human tears 110. Copyright 2021, Elsevier B.V. (D) CNP-PEG-GOx-laden contact lenses for colorimetric monitoring tear glucose 111. Copyright 2021, American Chemical Society.…”

Nanozyme-based colorimetric biosensor with a systemic quantification algorithm for noninvasive glucose monitoring

“…Recently, Park et al . developed a biocompatible biosensor of a nanoparticle-embedded contact lens (NECL) composed of complexes of cerium oxide nanoparticles (CNPs), glucose oxidase (GOx), and a polyethylene glycol (PEG) 20 . After reacting with tear glucose and H 2 O 2 , NECLs are oxidized and changed into a yellowish color.…”

“…Nanozyme-based biosensors mainly detect color in a qualitative manner 19 , 20 . Therefore, for quantitative measurement of glucose concentration, many algorithms have been developed in different color spaces (RGB, CMYK, HSB/HSL, CIE XYZ, L*a*b*, and YUV models) to analyze color variations.…”