Anthocyanin-Functionalized Contact Lens Sensors for Ocular pH Monitoring

Abstract

Anthocyanins are bioactive compounds naturally found in a variety of leaves, fruits, and vegetables. Anthocyanin pigments undergo a modification in their chemical structure when exposed to different concentrations of hydrogen ions, and they were extensively studied to be used as active elements in biocompatible pH sensors. The ocular pH is a significant parameter to assess the ocular physiology in cases of postocular surgery, keratoconjunctivitis, and ocular rosacea. Contact lenses have the potential to be used as medical diagnostic devices for in situ continuous monitoring of the ocular physiology. Here, anthocyanin-functionalized contact lenses were developed as wearable sensors to monitor the ocular pH. Anthocyanin pigments were extracted from Brassica oleracea and used to functionalize the polymeric matrices of commercial soft contact lenses by soaking and drop-casting processes. Contact lenses responded to the physiological ocular pH of 6.5, 7.0, and 7.5, exhibiting a systematic color shift from pink (pH 6.5) to purple (pH 7.0) and blue (pH 7.5). The functionalization of contact lens sensors was evaluated as a function of the dye concentration. Quantitative values were obtained by comparing the RGB triplets of the colors obtained with the naturally extracted dye and with delphinidin chloride dye in 0.0 to 1.5 mmol L–1 aqueous solution. The functionalization of contact lenses was studied as a function of the soaking time, resulting in best results when soaking for 24 h. The dye leakage from the contact lenses in deionized water was evaluated, and a negligible leakage after 18 h was observed. Poly-2-hydroxy ethylmethacrylate contact lenses were fabricated and cross-linked with anthocyanin dye, resulting in a slight color shift upon pH changes from 6.5 to 7.4. Contact lens pH sensors may be used to continuously monitor the ocular pH at point-of-care settings.

<p>Healthcare Applications of pH-Sensitive Hydrogel-Based Devices: A Review</p>

“…Dox attached to an HPMA polymer backbone, through degradable hydrazone linkages combined with spacers stable in physiological conditions, was shown to release DOX sufficiently in the mild acidic environment. 11 The effective release of DOX was found at pH 5.0 while a slight release was seen at the physiological pH, demonstrating that the hydrogel is more stable in physiological conditions. Dong et al (2017) fabricated a Salecan-based pH-sensitive hydrogel for controlled insulin delivery.…”

“…A slow and stable release of DOX was shown in this study and it was found that NIR irradiation accelerated the release of the drug. The release of Dox drug was also investigated in the work of Etrych et al 11 using water-soluble polymer N-(2-hydroxypropyl)methacrylamide (HPMA). Dox attached to an HPMA polymer backbone, through degradable hydrazone linkages combined with spacers stable in physiological conditions, was shown to release DOX sufficiently in the mild acidic environment.…”

“…Hydrogels are promising for pH sensing due to their wide measuring range. 4,11 Hydrogel-based sensors may be miniaturized and hence are of great importance when combined into microsystems. 12,13 Microcantilevers fabricated using silicon wafers have shown significant sensitivity with the detection of microscale changes in pH.…”

Hydrogel-Based Colloidal Photonic Crystal Devices for Glucose Sensing

“…A recent work reported a CPC contact lens with the properties of anti-ultraviolet and blue light reflection [89]. More recently, HCPC contact lenses with various functionalities, such as pH monitoring, drug releasing, and eye pressure sensing, have been developed for point-of-care ophthalmic health monitoring [90][91][92].…”

Prospects for Additive Manufacturing in Contact Lens Devices

“…[ 15,16,98–101 ] Recently, smart CLs are extensively studied to continuously monitor vital signs from ocular conditions (e.g., dry eye, glaucoma) to monitor diseases such as diabetes [ 98,102–107 ] as well as physiological level of pH. [ 102,108 ] Figure shows examples of the smart CLs. Figure 10A shows the prototype of Google's electronic CL that may measure glucose in tears, and correct vision for individuals suffering from presbyopia.…”