Game of Exosomes

Early cancer detection is an elusive, but highly appealing goal – especially in cancers that often go undiagnosed until the advanced stages. One example is ovarian cancer, in which well over half of women are diagnosed at stage III or IV (1). Now, a new lab-on-a-chip device can detect cancer quickly and noninvasively in a droplet of blood or plasma by identifying tumor exosomes (2) – extracellular vesicles that play an important role in cell-to-cell communication.

Although exosomes were historically thought of as cellular “trash bags,” recent discoveries have revealed their unanticipated significance. “In the past decade, we have realized that exosomes deliver molecular instructions in the form of nucleic acids and proteins that affect the function of other cells,” says lead author Yong Zeng. When produced by tumor cells, exosomes stimulate tumor growth and induce metastasis, making them ideal targets for cancer detection. But their rarity during the early stages of cancer makes spotting them a challenge that requires an ultra-sensitive biosensor.

Existing methods for exosome detection are not only time-consuming, but also suffer from low sensitivity and poor isolation efficiency. How did Zeng’s team overcome these issues? “When particles move close to the sensor surface in microscale channels, they’re separated by a small layer of liquid. We used a 3D nanoporous herringbone structure to increase the surface area for exosome capture within the chip and physically push exosomes into contact with the chip’s sensing surface, which contains antibodies specific to the proteins present on exosomes.” Zeng likens this approach to draining a million tiny sinks to allow items floating on the surface to touch the bottom.

When the device was tested in ovarian cancer patients, it was able to detect tumor exosomes in miniscule amounts of plasma. Specifically, the team discovered that a protein called folate receptor alpha is present in ovarian cancer exosomes, but not in those from healthy controls. The fact that the device identified exosomal folate receptor alpha in the plasma of early-stage ovarian cancer patients underlines its potential suitability as a biomarker detector.

One of the most attractive aspects of the device is its accessibility; the lithography-free fabrication method permits low-cost, rapid, and large-scale production of 3D nanostructured patterns. Without the need for high-tech nanofabrication equipment, the device could easily translate into any clinical setting. So what’s next? The team intends to pursue clinical applications by targeting multiple cancer types. “Although there is still a long way to go before we validate the device for clinical use, its potential adaptability to different diseases and biological targets – such as cells and viral particles – gives us great optimism for the future.”