Laser-inscribed contact lens sensors for the detection of analytes in the tear fluid

We report the design, construction, and testing of a contact lens with an integrated amperometric glucose sensor, proposing the possibility of in situ human health monitoring simply by wearing a contact lens. The glucose sensor was constructed by creating microstructures on a polymer substrate, which was subsequently shaped into a contact lens. Titania sol-gel film was applied to immobilize glucose oxidase, and Nafion® was used to decrease several potential interferences (ascorbic acid, lactate, and urea) present in the tear film. The sensor exhibits a fast response (20s), a high sensitivity (240 μA cm(-2) mM(-1)) and a good reproducibility after testing a number of sensors. It shows good linearity for the typical range of glucose concentrations in the tear film (0.1-0.6 mM), and acceptable accuracy in the presence of interfering agents. The sensor can attain a minimum detection of less than 0.01 mM glucose. Published by Elsevier B.V.

Low-cost, robust, and reusable continuous glucose monitoring systems that can provide quantitative measurements at point-of-care settings is an unmet medical need. Optical glucose sensors require complex and time-consuming fabrication processes, and their readouts are not practical for quantitative analyses. Here, a wearable contact lens optical sensor was created for the continuous quantification of glucose at physiological conditions, simplifying the fabrication process and facilitating smartphone readouts. A photonic microstructure having a periodicity of 1.6 μm was printed on a glucose-selective hydrogel film functionalized with phenylboronic acid. Upon binding with glucose, the microstructure volume swelled, which modulated the periodicity constant. The resulting change in the Bragg diffraction modulated the space between zero- and first-order spots. A correlation was established between the periodicity constant and glucose concentration within 0–50 mM. The sensitivity of the sensor was 12 nm mM–1, and the saturation response time was less than 30 min. The sensor was integrated with commercial contact lenses and utilized for continuous glucose monitoring using smartphone camera readouts. The reflected power of the first-order diffraction was measured via a smartphone application and correlated to the glucose concentrations. A short response time of 3 s and a saturation time of 4 min was achieved in the continuous monitoring mode. Glucose-sensitive photonic microstructures may have applications in point-of-care continuous monitoring devices and diagnostics at home settings.

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.