Rapid diagnosis of pancreatic cancer with graphene sensor array

Researchers from the UK, China and Spain have utilized arrays of graphene sensors to detect exosomes specific to pancreatic cancer (PC) from patient blood plasma within 45 minutes. The work demonstrates that Graphenea’s wafer-scalable graphene field-effect transistor (GFET) array platform enables meaningful clinical results, and that the GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of PC.

The work, recently published in the journal ACS Nano, is based on GFET arrays produced in the Graphenea Foundry on 4” and 6” wafers. The foundry process ensures batch-to-batch reproducibility and high-quality reliability, with a >95% device yield. The graphene devices were functionalized with antibodies specific to the target exosome, making use of the linker molecule tetrakis(4-carboxyphenyl) porphyrin (TCPP) that binds to graphene on one side and the antibody on the other side. The sensors were used to detect the GPC-1 cancer exosome, which is abundant in the plasma of PC patients. Detection was performed with an electric readout system that monitored the electrical properties of the devices in a control state, and in the presence of GPC-1. It is confirmed that the concentration of the exosome is an order of magnitude higher in individuals that have PC than in healthy ones. The concentration of GPC-1 in blood plasma was also found to be dependent on the stage of the cancer, growing as the cancer progresses. In the course of the research, the measurement protocol was fine-tuned by including novel steps such as sensing device pre-selection and refinement of linker choice.

The study involved 26 patients, both healthy and with PC. While some overlap existed in the exosome levels between the two groups, the density of exosomes on the GFET surface and the GFET response were notably higher for cancer patients. Through Western blot analysis and immunogold transmission electron microscopy (IG-TEM), it was observed that GPC-1 proteins were more strongly expressed on PC exosomes than on healthy ones. This higher expression enhances the binding affinity, enabling GPC-1 to exhibit greater specificity to cancer exosomes, leading to an amplified signal in the GFET biosensors and improved accuracy of detection. The work is the most impressive demonstration to date of clinical detection carried out with GFETs.

PC poses a significant challenge due to its elusive early detection and poor survival rates. Patients often seek medical attention only in advanced stages when they experience noticeable symptoms. However, early detection is key to improving survival rates. The GFET-based biosensors, being sensitive to GPC-1 at all stages of cancer, provide a promising avenue for early detection of PC. Use of the GFET technology enables a general screening for pancreatic cancer which is unfeasible with other existing methods, due to cost or lack of a Point of Care approach.

The test involves using a drop of 20 μL of whole plasma sample, and it can be completed in less than 45 minutes. A faster readout electronic system could further reduce the detection time. The GFET-based test demonstrates the ability to detect cancer at all stages, capitalizing on the unique properties of cancer exosomes and the high sensitivity of GFETs.

The test, facilitated by a portable platform with read-in/read-out electronics, is simple and user-friendly, requiring no specialized training to perform. Additionally, the inclusion of an internal control on the GFET chip substantially reduces false positive rates, further enhancing the accuracy of detection. The test procedure comprises four straightforward steps, including two blank measurements, incubation, and multiple rinsing, eliminating the need for skilled operators. Furthermore, the GFET platform is adaptable, allowing for the simultaneous detection of multiple PC biomarkers on the same chip. This GFET technology can be reconfigured to detect other disease biomarkers, potentially revolutionizing diagnosis in various medical contexts.

Importantly, the GFET chip is CMOS compatible and can be produced on a large scale, significantly reducing costs and ensuring minimal device-to-device variation with a high yield. This scalability and cost-effectiveness make the GFET platform a promising tool for widespread and accessible cancer screening and diagnostic purposes.