A Microchambers Containing Contact Lens for the Noninvasive Detection of Tear Exosomes

Abstract

Exosomes, a form of small extracellular vesicles, play a crucial role in the metastasis of cancers and thus are investigated as potential biomarkers for cancer diagnosis. However, conventional detection methods like immune‐based assay and microRNA analyses are expensive and require tedious pretreatments and lengthy analysis time. Since exosomes related to cancers are reported to exist in tears, a poly(2‐hydroxyethyl methacrylate) contact lens embedded with antibody‐conjugated signaling microchambers (ACSM‐PCL) capable of detecting tear exosomes is reported. The ACSM‐PCL exhibits high optical transparency and mechanical properties, along with extraordinary biocompatibility and good sensitivity to exosomes. A gold nanoparticle colorimetric assay is employed to visualize captured exosomes. The ACSM‐PCL can detect exosomes in the pH range of 6.5–7.4 (similar to the human tear pH) and have a strong recovery yield in bovine serum albumin solutions. In particular, the ACSM‐PCL can detect exosomes in various solutions, including regular buffer, cell culture media from various cell lines, and human tears. Finally, the ACSM‐PCL can differentiate expression of exosome surface proteins hypothesized as cancer biomarkers. With these encouraging results, this ACSM‐PCL is promised to be the next generation smart contact lens as an easy‐to‐use, rapid, noninvasive monitoring platform of cancer pre‐screening and supportive diagnosis.

Microfluidic contact lenses for ocular diagnostics and drug delivery

“…[12] The detection of biomarkers in tears was demonstrated through the measurement of the exosome-derived biomarkers via antibody-conjugated signaling microchambers (ACSM) in poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses (PCL). [23] Exosomes are promising biomolecules used as diagnostic markers since they provide unique genetic and proteomic information about the parent cells. However, the isolation and characterization methods of exosomes are complicated and timeconsuming.…”

“…[64,65] The diversity of biomarkers contained in the tear fluid can reveal ocular conditions in a continuous manner. [23] However, the validation of these contact lenses will require a robust clinical trial design. In addition to diagnosis or drug delivery functions, it is critical to provide refractive index correction functions together for patients [9] who may require continuous or periodic usage.…”

“…The device is a highly promising minimally‐invasive monitoring platform for cancer screening (Figure 2). [ 23 ]…”

“…Visualization of tear exosomes in a microchamber‐structured contact lens using AuNP‐tagged anti‐CD9 antibodies. Reproduced with permission [23]. Copyright 2022, Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…[5,18,19] Contact lenses have further evolved in the last decade by integrating smart microfluidic sensing systems, allowing the screening and diagnosis by tear analyte detection and therapy through drug delivery. [8] In addition to vision correction [9] and health monitoring through tear analytes, [20] functional contact lens technologies have been developed [21] for providing aseptic ocular screening with high quality, [4] disease diagnostics, [22,23] and drug delivery. [24] Minimally-invasive nature of the application and user comfort make contact lenses an attractive platform.…”