Human tears could carry a flood of useful information.
With just a few drops, a new technique can spot eye disease and even glimpse signs of diabetes, scientists report July 20 in ACS Nano.
We wanted to demonstrate the potential of using tears to detect disease, says Fei Liu, a biomedical engineer at Wenzhou Medical University in China. It’s possible the droplets could open a window for scientists to peer into the entire body, he says, and one day even let people quickly test their tears at home.
Like saliva and urine, tears contain tiny sacs stuffed with cellular messages (SN: 9/3/13). If scientists could intercept these microscopic mailbags, they could offer new intel on what’s happening inside the body. But collecting enough of these sacs, called exosomes, is tricky. Unlike fluid from other body parts, just a trickle of liquid leaks from the eyes.
So Liu’s team devised a new way to capture the sacs from tiny volumes of tears. First, the researchers collected tears from study participants. Then, the team added a solution containing the tears to a device with two nanoporous membranes, vibrated the membranes and sucked the solution through. Within minutes, the technique lets small molecules escape, leaving the sacs behind for analysis.
The results gave scientists an eyeful. Different types of dry-eye disease shed their own molecular fingerprints in people’s tears, the team found. What’s more, tears could potentially help doctors monitor how a patient’s diabetes is progressing.
Now, the scientists want to tap tears for evidence of other diseases as well as depression or emotional stress, says study coauthor Luke Lee, a bioengineer at Harvard Medical School. This is just the beginning, he says. Tears express something that we haven’t really explored.
Exosomes with membrane structures can encapsulate and protect their cargos, thus becoming a promising source for disease early detection. Tears can be non-invasively and self-collected from patients for exosome analysis. However, the tear-exosome-based disease analysis has rarely been reported so far. Recording exosomes from trace samples for further analysis is necessary in exploring the tear-exosome-based disease world. We have recently developed a harmonic oscillation of a nanopore membrane for the ultrafast exosome isolation system to address the limitation of commercial methods in analyzing samples with narrow volume ranges and time-consuming processes. We have modified and expanded it to perform rapid tear-exosome purification while allowing in situ detection and biomarker discovery.
We first report that iTEARS is suitable for purifying small extracellular vesicles, especially exosomes, by characterizing the submicroscopic structures and detecting the specific proteins of tear exosomes. We select 5 mL as the initial volume of 1X PBS to contain teardrops, according to its suitable liquid level in covering the strips in a 15 mL centrifuge tube. The iTEARS processes samples with an extensive range in both volume and dilution, which conclude a limit of process volume of 1 mL for NTA, WB, and on-device detection of the membrane proteins. Compared with the conventional ELISA, iTEARS allows direct immune-targeting of exosomes without precapturing them using additional antibodies or antigens. The differential signals between CD9 and CD81 are probably due to the weaker essential expression and packaging efficiency of CD81 in tear exosomes, which is similar to the WB results. In addition, the different performances of primary antibodies for protein detection might also give different signals. However, both CD9 and CD81 showed linear curves to the input sample volume and a relatively low LOD (0.5–1 mL of sample volume) compared to TSG101, Alix, and Mac-2BP. Additionally, despite the applicability of commercial strategies for tear studies, we demonstrate the isolation and analysis performance of iTEARS in tear sEV yield, purity, and efficiency by a comparative analysis.
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