- Pancreatic cancer is often diagnosed late, leading to poor prognosis. Current diagnostic methods are invasive and time-consuming.
- The existing diagnostic tools also lack precision and are costly, ultimately making the early detection of pancreatic cancer a challenge.
- Professor Norbert Klein, Dr Sami Ramadan, and Dr Tianyi Yin from the Department of Materials at Imperial College London have collaborated with their colleagues to develop a solution, allowing for quick and accurate detection of pancreatic cancer exosomes in blood plasma samples within 45 minutes, potentially developing early diagnosis and improving patient outcomes.
Pancreatic cancer is a highly lethal disease, often diagnosed at advanced stages contributing to its poor prognosis. Early detection is crucial for improving patient outcomes, as the five-year survival rate for pancreatic cancer is less than 15% but significantly higher if diagnosed early. Current diagnostic methods, such as imaging techniques including CT and MRI or even tissue biopsies, are invasive, expensive, and time-consuming.
Professor Norbert Klein, Dr Sami Ramadan, and Dr Tianyi Yin from the Department of Materials at Imperial College London in the UK have collaborated with their colleagues to develop a robust method to detect pancreatic cancer exosomes in patients within 45 minutes, by simply collecting blood plasma samples.
Exosomes as diagnostic weapons
The research team opted to detect cancer by extracting blood samples from the patients and detecting vesicles, known as exosomes. Exosomes exist on a nanoscale level and are invisible to the naked eye.
They are sacs emitted by cells including cancer cells, facilitating cell-to-cell communication and carrying crucial information about the cell’s characteristics. These sacs transport a variety of molecules, including proteins, DNA, and RNA, providing valuable insights into the cell’s origin and status.
Current diagnostic methods for pancreatic cancer, such as CT and MRI or even tissue biopsies, are invasive, expensive,
and time-consuming.
Exosomes released by cancer cells may carry distinct molecules that serve as biomarkers for disease detection. Specifically, exosomes originating from pancreatic cancer-initiating cells carry specific protein markers, including GPC-1 (Glypican-1). Western blot, enzyme-linked immunosorbent assay (ELISA), and flow cytometry are laboratory techniques commonly used to detect and analyse specific exosomal proteins in biological samples. These methods are expensive and time-intensive.
The GFET sensor array platform
The research team has developed a portable graphene sensor array platform, called graphene field-effect transistors (GFETs), capable of detecting pancreatic cancer exosomes in patients’ blood plasma within 45 minutes. This allows for non-invasive and repeated sampling, which is essential for early cancer detection and monitoring disease progression. The platform consists of graphene sensors coated with antibodies, also known as immunoglobulins, which are specific to proteins found on pancreatic cancer exosomes.
During the diagnostic test, a small drop of blood plasma (equal to 0.02 ml) is placed on the sensor array. Antibodies on the sensors bind to proteins and other molecules on pancreatic cancer exosomes, causing a change in the electrical conductivity of the graphene sensors. This change can be measured to identify the presence of pancreatic cancer exosomes.
To enhance accuracy, the researchers implemented a differential measurement to subtract interference signals caused by other components present in the patients’ blood, including proteins, enzymes, and other biomolecules that could potentially interfere with the graphene biosensors and provide inaccurate results.
The success of the platform developed by Ramadan, Yin, and their collaborators stems from a combination of innovative design features and meticulous quality control measures. At the heart of the platform is an on-chip integrated sensor array, which combines both sensing and control channels to enhance selectivity and sensitivity in detecting pancreatic cancer exosomes.
This integrated approach allows for precise detection of exosomes while minimising interference from other substances. Additionally, the platform incorporates internal controls to ensure consistent performance, with strict quality control protocols implemented during graphene production to maintain sensor reliability.
Successful detection in pancreatic patients
The group successfully tested the platform within the clinic. They collected blood plasma samples from 18 pancreatic cancer patients and 8 healthy controls (healthy people who were not suffering from pancreatic cancer). Testing these samples on the GFET platform, they successfully managed to accurately distinguish between the two groups in all cases.
The research demonstrates the potential of the portable GFET sensor technology for early pancreatic cancer diagnosis, providing a rapid, sensitive, and specific diagnostic platform.
Even more remarkable was the fact that they were able to detect pancreatic cancer exosomes even at early stages (stage 1 and stage 2). This is significant because early detection of cancer is often challenging, and being able to identify cancer-related markers at such an early stage (stage 1) could potentially lead to more effective treatment and improved patient outcomes.
Transforming pancreatic cancer diagnosis
The research demonstrates the potential of the portable GFET sensor technology for early pancreatic cancer diagnosis, providing a rapid, sensitive, and specific diagnostic platform. Furthermore, this technology can be readily adapted to target other pancreatic cancer biomarkers, including proteins and microRNAs.
The platform presents rapid, cost-effective, and user-friendly diagnostics, which could significantly improve early pancreatic cancer detection and management. If validated in additional clinical trials and for detecting multiple pancreatic cancer biomarkers, it could become a crucial tool for addressing this deadly disease.
How do you envision the future of cancer diagnostics evolving with the integration of innovative technologies like GFETs?
Cancer diagnostics with current techniques, such as MRI, CT, and endoscopic ultrasound, are expensive. It also suffers from inaccurate predictions when the cancer is in the early stage. The cancer diagnostics with GFET will be more cost-effective, and offers direct and fast detection in point-of-care testing. Additionally, the use of biosensors like GFET allows screening of cancer, enabling early disease detection.
Could you discuss the potential limitations or challenges associated with translating the GFET sensor array platform from laboratory testing to clinical application, and how do you plan to address these challenges in future research or development?
The presented research is just a proof-of-principle study with a small number of clinical samples. Further validation is required with a larger number of patients and control group samples. Additionally, there is no single biomarker that can be used for diagnostic of disease – multiple biomarkers need to be used in combinations. We plan to further improve the design of our integrated GFET sensor array to achieve multiple detections in the same plasma sample. Meanwhile, we need to work closely with the clinicians in validating the potential biomarkers that could be used in combination for the diagnostic of disease.
How could GFET work differently when it comes to using other samples, such as urine or saliva?
The developed GFET can be easily adapted to detect biomarkers in other samples such as urine or saliva. The integrated GFET sensor array and the developed protocol allows the GFET biosensor in detecting biomarkers in all kinds of physiological solutions. We have showcased the detection of biomarkers in UTM in one of our previous studies.
