Abstract
The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging.
Highlights
The Na+ ion concentration in the tears of healthy individuals ranges between 120–165 mmol L−1.30 in dry eye syndrome caused by MGD or LGD, Na+ ion concentration in human tear increase was reported to be significant, which can be detected by a sensor sensitivity of ∼3.0 mmol L−1.31 divalent metal ion concentration was found to be different in MGD and LGD
To design a paper-based microfluidic device that can operate with tear fluid samples (
The concentration of Ca2+ ions in tear fluid of healthy individuals is 0.4–1.1 mmol L−1.42 in dry eye syndrome caused by MGD or LGD, tear Ca2+ ion concentration increases 2.5% and 5.0%, respectively
Summary
The diluted artificial tear fluid diffused through the main channel of the paper-based microfluidic device to four branches to interact with fluorescent probes in the sensing regions. As the concentration of Na+ ions in the presence of diaza-15-crown-5 on G1 matrix increased from ion-free buffer solution (Tris, pH 7.4, 150 mmol L−1) to 200 mmol L−1, the fluorescence intensity of the probe increased by 1.9 fold (Fig. 3d inset). The fluorescence images of probes at different artificial tear fluid compositions on paper-based microfluidic device were captured by an iPhone 6S camera positioned over a wide-angle lens in the readout device using a smartphone app (Shoot) (Fig. 6d–f and S17‡).
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