New exosome sensor could enable early and fast detection of pancreatic cancer

Researchers at Imperial College London have developed a new platform which could support the rapid diagnosis of pancreatic cancer.

Pancreatic cancer is the second most fatal cancer and the seventh-leading cause of cancer deaths worldwide. Despite recent progress in cancer diagnosis and treatment, the overall survival rate in this type of cancer has only slight improvement over the past decade.

Early detection plays a crucial role in enhancing the survival rate for pancreatic cancer. Existing diagnostic methods for pancreatic cancer include imaging tests and tissue biopsies, which can also be invasive, expensive, and time-consuming. Many patients also do not present symptoms in the early stages, therefore researchers set out to develop a platform that could detect and diagnose pancreatic cancer before a patient develops advanced symptoms.

Their new findings could lead to the development of a new non-invasive diagnostic tool for pancreatic cancer.

New methods of detection

The key to developing the new sensor was the investigation of exosomes. Exosomes are nanoscale vesicles secreted by all cells, including cancer cells. They contain a variety of molecules, including proteins, DNAs, and RNAs, which can provide valuable information about the cell that released them. One of the most important advantages of exosomes for cancer detection is that they can be isolated from a variety of bodily fluids, such as blood, urine, and saliva. This can allow for non-invasive and repeated sampling, which is essential for early cancer detection and the monitoring of disease progression.

Researchers found that pancreatic cancer exosomes have unique characteristics that can be used to distinguish them from exosomes released by healthy cells. Using these findings, they successfully engineered a novel sensor platform that can distinguish unique characteristics in pancreatic cancer exosomes, enabling for the detection of these exosomes in patient blood plasma samples in a mere 45 minutes.

How does the sensor work?

The sensor is made up of an array of graphene sensors, each of which is coated with a different antibody specific for a different protein or other molecule found on pancreatic cancer exosomes.

To use the sensor, a small drop of blood plasma from a patient is placed on the array. The antibodies on the sensor bind to proteins and other molecules on the pancreatic cancer exosomes, and this causes a change in the electrical conductivity of the graphene sensor. This change in conductivity can be measured and used to identify the presence of pancreatic cancer exosomes in the blood plasma sample.

Researchers developed a simple and user-friendly portable platform to perform the test, with easy to read electronics that are accessible to individuals without prior experience with medical devices.

Physiological fluids such as plasma and blood are complex matrices containing many proteins, enzymes, and other biomolecules that can interact with the graphene biosensors. Researchers used differential measurement to distinguish between the signal from the cancer exosomes andother interfering signals.

They were able to test the graphene sensor array using blood plasma samples from 18 pancreatic cancer patients and eight people who did not have cancer. They found the platform was able to accurately discriminate between the two groups in one hundred percent of cases. The platform array was also able to detect pancreatic cancer exosomes at the early stages, including stages one and two.

Schematics of detection of PDAC exosomes using GFETs with portable electronics
and real-time detection results

The total detection time from applying blood plasma on the GFETs to results is less than 45 min. The zoomed in area shows schematics of the functionalization of graphene with TCPP (43) and the GPC-1 antibody. The middle-right images are fluorescence images showing higher density of exosomes on the GFET surface for the PDAC patients’ samples than the healthy controls. The top-right images are TEM images with immunogold labeling with GPC-1 to compare the GPC-1 protein expressions on healthy and cancerous exosomes.

What could this mean for the future?

The development of the new graphene sensor platform could be a significant step forward in the fight against pancreatic cancer.

If the findings are confirmed in further clinical trials and in the detection of multiple pancreatic cancer biomarkers, this sensor could emerge as an important and non-invasive diagnostic tool for diagnosing pancreatic cancer in its early-stages, when treatment options are most effective for patients.

SourceImperial College London

Yin T, Xu L, Gil B, Merali N, Sokolikova MS, Gaboriau DCA, Liu DSK, Muhammad Mustafa AN, Alodan S, Chen M, Txoperena O, Arrastua M, Gomez JM, Ontoso N, Elicegui M, Torres E, Li D, Mattevi C, Frampton AE, Jiao LR, Ramadan S, Klein N. (2023) Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients’ Blood Plasma Samples. ACS Nano 7(15):14619-14631. [article]

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