Exosome-based diagnostic module for early cancer detection

Background Exosomes are membrane-bound spherical structures (10-150 nm) secreted into the interstitial fluid by all cell types ubiquitously. They carry signatures specific to the parent cell making them excellent biomarkers for the early detection of cancer.

They are present in various bodily fluids even at the early stages of cancer but currently there is no clinical device available to accurately detect their presence in patient samples for early cancer screening.

Aim We aim to develop a diagnostic chip, the CanScreen (Cancer Screening), that can screen for the presence of ovarian cancer-related exosomes and thereby detect ovarian cancer at its early stages of onset.

CanScreen will achieve this by (1) size sorting and enriching different subpopulations of exosomes followed downstream by (2) capturing and detecting exosomes presenting ovarian cancer-specific surface receptors, and finally (3) calculating the percentage of cancerous exosomes to the total population.

Method The device will be a handheld microfluidic chip.

By integrating nanoporous membranes of various pore sizes within the microfluidic channels we aim to isolate and size-sort the target exosome subpopulations. Size-sorting especially will increase the sensitivity of the device.

Downstream of the membranes, we will functionalize the microfluidic channels with fluorophore-labelled antigens targeting ubiquitous and ovarian cancer-specific exosomal surface receptors.

The binding of the target exosomes and the subsequent fluorescence signal will be measured to determine the presence and degree of the early ovarian cancer exosomes in samples.

By also calculating the ratio of cancerous to total exosome numbers, we can obtain an indirect measure of cancerous cell numbers and hence disease progression. The proof of concept studies will be validated using non-clinical samples for the primer study.

How the results of this research will be used Once validated, CanScreen will enable the rapid in situ isolation of specific target subpopulations of exosomes from cell-free patient blood samples and screen for biomarkers.

For the primer award, we will use early ovarian cancer as the disease model, following from this, the platform technology of CanScreen can be extended to the early detection of other cancerous types.

By establishing the fabrication protocol, it will be straightforward to adapt the detection component to different exosome biomarkers specific to other cancer types.