Smart contact lenses enable cancer diagnostics, screening

Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have led the development of a contact lens that can capture and detect exosomes — nanometre-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. Described in the journal Advanced Functional Materials, the lens was designed with microchambers bound to antibodies that can capture exosomes found in tears.

The antibody-conjugated signalling microchamber contact lens (ABSM-CL) can be stained for detection with nanoparticle-tagged specific antibodies for selective visualisation. This offers a potential platform for cancer pre-screening and a supportive diagnostic tool that is designed to be easy, rapid, sensitive, cost-effective and non-invasive.

Exosomes are formed within most cells and secreted into many bodily fluids, such as plasma, saliva, urine and tears. Once thought to be the dumping grounds for unwanted materials from their cells of origin, it is now known that exosomes can transport different biomolecules between cells. It has also been shown that there is a wealth of surface proteins on exosomes — some that are common to all exosomes and others that are increased in response to cancer, viral infections or injury. In addition, exosomes derived from tumours can strongly influence tumour regulation, progression and metastasis.

Because of these capabilities, there has been much interest in using exosomes for cancer diagnosis and prognosis/treatment prediction. However, this has been hampered by the difficulty in isolating exosomes in sufficient quantity and purity for this purpose. Current methods involve tedious and time-consuming ultracentrifuge and density gradients, taking at least 10 hours to complete. Further difficulties are posed in detection of the isolated exosomes; commonly used methods require expensive and space-consuming equipment.

The TIBI team leveraged their expertise in contact lens biosensor design and fabrication to eliminate the need for these isolation methods by devising their ABSM-CL for capturing exosomes from tears — a cleaner source of exosomes than blood, urine and saliva. They also facilitated and optimised the preparation of their ABSM-CL by the use of alternative approaches. When fabricating the microchambers for their lens, the team used a direct laser cutting and engraving approach rather than conventional cast moulding for structural retention of both the chambers and the lens.

The team also introduced a method that chemically modified the microchamber surfaces to activate them for antibody binding. This method was used in place of standard approaches, in which metallic or nanocarbon materials must be used in expensive cleanroom settings. The team then optimised procedures for binding a capture antibody to the ABSM-CL microchambers and a different (positive control) detection antibody onto gold nanoparticles that can be visualised spectroscopically. Both these antibodies are specific for two different surface markers found on all exosomes.

In an initial validation experiment, the ABSM-CL was tested against exosomes secreted into supernatants from 10 different tissue and cancer cell lines. The ability to capture and detect exosomes was validated by the spectroscopic shifts observed in all the test samples, in comparison with the negative controls. Similar results were obtained when the ABSM-CL was tested against 10 different tear samples collected from volunteers.

In final experiments, exosomes in supernatants collected from three different cell lines with different surface marker expressions were tested against the ABSM-CL, along with different combinations of marker-specific detection antibodies. The resultant patterns of detection and non-detection of exosomes from the three different cell lines were as expected, thus validating the ABSM-CL’s ability to accurately capture and detect exosomes with different surface markers.

“Exosomes are a rich source of markers and biomolecules which can be targeted for several biomedical applications,” said TIBI Director and CEO Dr Ali Khademhosseini. “The methodology that our team has developed greatly facilitates our ability to tap into this source.”

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