Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have created a contact lens that can capture and detect exosomes, which are nanometer-sized vesicles present in physiological fluids that have the potential to be diagnostic cancer biomarkers.
The lens was designed with microchambers bound to antibodies that can capture exosomes found in tears. This nanoparticle-tagged specific antibody can be used to detect and selectively visualize this antibody-attached signaling microchamber contact lens (ABSM-CL).
This provides a potential platform for cancer pre-screening and a non-invasive, quick, easy, accurate, and cost-effective diagnostic tool.
Most cells produce exosomes, which are then discharged into various physiological fluids like plasma, saliva, urine, and tears. It is now known that exosomes can carry various biomolecules between cells, contrary to the earlier belief that they serve as the dumping grounds for unwanted materials from their cells of origin.
It has also been demonstrated that exosomes include a wide variety of surface proteins, some of which are present on all exosomes while others are produced in greater quantities in response to cancer, viral infections, or injury. Exosomes produced by tumors can also have a significant impact on the regulation, development, and metastasis of malignancies.
These qualities have sparked a lot of interest in the use of exosomes for cancer diagnosis and treatment prediction.
Current procedures require laborious ultracentrifuge and density gradients that take at least ten hours to finish. The detection of the isolated exosomes presents additional challenges because conventional techniques demand expensive, space-consuming equipment.
The TIBI team developed its ABSM-CL for capturing exosomes from tears, an ideal and cleaner source of exosomes than blood, urine, and saliva, in order to eliminate the necessity for these isolation procedures. This was done by utilizing their expertise in contact lens biosensor design and production.
By using alternate methods, they also facilitated and improved the preparation of their ABSM-CL. The team used a direct laser cutting and engraving method over traditional cast molding when making the microchambers for their lens in order to maintain the structural integrity of both the chambers and the lens.
The scientists also developed a technique that chemically activated the microchamber surfaces for antibody binding. Instead of using costly clean-room environments and metallic or nanocarbon materials, this strategy was adopted instead.
The team then optimized procedures for binding a capture antibody to the ABSM-CL microchambers and a different (positive control) detection antibody onto gold nanoparticles that can be visualized spectroscopically. These two antibodies are each specific for two distinct exosome surface indicators.
The ABSM-CL was put to the test against exosomes released into supernatants from 10 different tissue and cancer cell lines in an early validation experiment. The spectroscopic shifts seen in all test samples in comparison to the negative controls served as proof that exosomes could be captured and detected. When the ABSM-CL was tested against ten different volunteer tear samples, the outcomes were similar.
Exosomes in supernatants from three different cell lines that express different surface markers were tested against the ABSM-CL in final studies along with various combinations of marker-specific detection antibodies. Exosome detection and non-detection patterns from the three different cell lines followed the expected patterns, demonstrating the ABSM-capability CL's to precisely capture and detect exosomes using various surface markers.
“Exosomes are a rich source of markers and biomolecules which can be targeted for several biomedical applications,” said Ali Khademhosseini, Ph.D., TIBI’s Director and CEO. “The methodology that our team has developed greatly facilitates our ability to tap into this source.”