NEW YORK – Armed with a €161,000 ($181,000) grant, researchers in Spain aim to develop a multisensor platform to detect microRNAs and long noncoding RNAs for the diagnosis of breast cancer.
The scientists from Catalan Institute of Nanoscience and Nanotechnology (ICN2) in Barcelona were awarded the funds to develop a point-of-care test as part of an EU-backed project called Serena. According to Arben Merkoçi, a research professor and group leader at the institute, the new project is aligned with ICN2's overall goal to develop test platforms for eventual clinical use.
"This has been and still is one of our main research lines, developing platforms for diagnostics," said Merkoçi. "We have been working in cancer, and on different platforms for the detection of cancer cells but also biomarkers related to different kinds of cancers," he said.
The title of ICN2's latest project, called Serena, is "development of an electrochemical multisensor platform for the simultaneous detection of emerging breast cancer biomarkers in a blood droplet." It has a start date of Feb. 1, 2022, and will run through January 2024. Funding was made available via the EU's Horizon 2020 program.
Merkoçi noted that the project has just been awarded, and much has yet to be decided about the course it will take. It is clear though that Serena will pair ICN2's competency in developing nanotechnology-based sensors, that whole blood will be the sample input, and that results will be delivered at the point of care. The resulting test could be used for both diagnosis and prognosis during treatment, according to the grant's abstract.
The abstract also states that the resulting system should be rapid, portable, and easy to use. It will rely on an electrochemical nanostructured device for detection of circulating miRNAs and long noncoding RNAs, or lncRNAs, which it calls "promising cancer biomarkers for liquid biopsy."
The researchers aim to pair the "advantages of nucleic acid analogues with those of graphene-nanoparticle hybrid composites" to develop a platform based on the use of "inexpensive screen printed electrodes, produced by cutting-edge green technologies," the abstract states.
As part of the Serena project, Marianna Rossetti, a researcher at the University Tor Vergata in Rome, will join Merkoçi’s group. Rossetti in an email said that markers such as miRNAs and lncRNAs are "attractive" for early breast cancer detection, prognosis, and response to therapy.
Specifically, noncoding RNAs, including miRNA and lncRNAs in cell-to-cell communication "exhibit implications in cancer progression and therapy resistance due to the ability of some ncRNAs to regulate gene expression outside of the cell of origin through extracellular vesicle-mediated transfer to recipient cells," said Rossetti. "These effects with their high abundance and stability support ncRNAs as promising potential cancer biomarkers for liquid biopsy," she said.
Rossetti went on to say that interplay between lncRNAs and miRNAs also has an impact on the tumorigenic process, and that their simultaneous detection will be relevant in clinical routine analysis in the future. She noted that techniques commonly used to detect ncRNAs, such as microarrays, next-generation sequencing, quantitative real-time PCR, and droplet microfluidics, require the use of "sophisticated instruments," as well as qualified personnel, "time-consuming procedures," and complex data interpretation.
"Therefore, there is an urgent need to develop devices to detect these novel biomarkers rapidly, at low cost, and with very high sensitivity and specificity," said Rossetti.
In addition to looking at miRNAs and lncRNAs, Rossetti and her colleagues are interested in detecting autoantibodies, a class of biomarkers produced as an immune response to cancer, the amount of which increases in the early stage of the disease. As such, the portable multisensor that the researchers intend to develop should be able to detect circulating miRNAs, lncRNAs, and autoantibodies in whole blood within minutes, without any need to pretreat samples, she said.
As head of the nanobioelectronics and biosensors group at ICN2, Merkoçi has been developing a suite of biosensors based around nanoparticles, nanotubes, graphene, nanochannels, and other materials that can be integrated into such a portable device for use by non-technicians. Graphene, a two-dimensional material, has been used to fabricate nanoplatforms for a variety of applications, such as printed microarrays and lateral flow assays for pathogen detection, he said.
"Of course, we are going to work with these platforms and have already been developing some sensors based on graphene," Merkoçi said of the project. The researchers also have different methods for detection, both electrical and optical, at their disposal for the Serena project. Merkoçi noted that ICN2's expertise in detection technologies can be used not only in cancer but in other applications, such as infectious disease testing, including for SARS-CoV-2.
"The detection technology is quite flexible," Merkoçi said. "For any type of application, you need to adopt the platform to optimize it and eventually make a series of adjustments to address new challenges, or a new type of detection," he continued.
Merkoçi has already played a role in developing technologies that have been commercialized.
One spinoff is Paperdrop Diagnostics, a Barcelona-based firm that develops rapid diagnostic tests based on paper microfluidics. Its first product, called Fastroke, can be used to predict the risk of ischemic stroke from a drop of blood.
ICN2 also collaborates with several clinical partners in the Barcelona area, including Hospital Sant Joan de Dèu to see its platforms tried and adopted for clinical use. According to Merkoçi, all of the work ICN2 has done in the area of nanosensors and detection assays will be harnessed in the Serena project.
"Serena will get advantages of these platforms and these will be adopted and improved," he said.
"This is an important project and aligned with objectives we have as a group and as an institute in the coming years focusing on cancer detection diagnostics."