NEW YORK – If all goes as planned, a consortium of European researchers and technology and services providers could be ready to launch at least one test for the early-stage detection of Alzheimer’s disease within three years, a goal it has been striving toward for nearly a year.
The consortium dubbed 2D-BioPAD is a Horizon Europe project with a budget of €6 million ($6.7 million) that commenced in October 2023 and will run through September 2027. It involves 11 partners and is being coordinated by Aristeidis Bakandritsos, a senior researcher at the Czech Advanced Technology and Research Institute (CATRIN) at Palacký University.
Q-Plan International, a Thessaloniki, Greece-based consulting firm that regularly participates in cross-disciplinary and cross-domain EU projects, is involved in the management of the project as well as the promotion and exploitation of its outcomes.
Apostolos Tsolakis, a senior project manager at Q-Plan, said in a recent interview that 2D-BioPAD aims to develop new technologies to create biosensors capable of supporting early-stage Alzheimer's disease detection. Such platforms will rely on graphene, an allotrope or form of carbon that consists of a single layer of atoms arranged within a honeycomb nanostructure.
The platform will be used to assay blood samples from patients for biomarkers associated with AD, making it a new entry in a market that has seen a flurry of interest recently, driven in part by the availability of new treatments for the disease, such as Eisai's Alzheimer's drug Leqembi (lecanemab).
"It would be a sensor that is much like a pregnancy test or glucose monitoring test, or even a SARS-CoV-2 test," said Tsolakis. "Something that is very compact and easy to use, with the view that it could be used by healthcare professionals in primary healthcare settings to support the early diagnosis of people at risk of Alzheimer's."
If patients' results suggest they may have the early stages of the disease, they could be directed to specialist centers or to healthcare professionals, such as neurologists, psychiatrists, or geriatricians, for follow-up. Tsolakis noted that the envisioned tests would be digital rather than optical sensors, so that results would be transmitted wirelessly to a mobile app. The platform would not only provide results in a positive-negative format but also detail the concentrations of the markers. While 2D-BioPAD is a year into its activities, it has "a lot of implementation and research to do," he acknowledged.
An initial panel for the envisioned tests has been selected, consisting of the markers Aβ1-40, Αβ1-42 (and their ratio), p-tau 217, NfL, and GFAP, Tsolakis said.
Tsolakis also pointed out that 2D-BioPAD is under the umbrella of the Graphene Flagship initiative, which is funded by the European Commission's Horizon Europe research and innovation program. The Graphene Flagship initiative works to advance Europe’s strategic autonomy in technologies that rely on graphene and other 2D materials. Graphene is viewed by the EU as having advantages over silicon due to its superior electrical conductivity, mechanical strength, stability, and flexibility. Additionally, graphene-based devices could offer lower energy consumption during operation, making it a promising material for next-generation electronics and sustainable technologies.
Each partner in 2D-BioPAD has its own area of expertise. UP-CATRIN, for example, is specialized in designing and synthesizing modified graphenes.
"For the past few years, we've been focused on the selective and controlled functionalization of graphene for applications in the energy and biomedical sectors," Bakandritsos said of his group's involvement. 2D-BioPAD is related to this interest, as his group will be working to achieve tailored and reproducible chemical functionalization of the biosensor's surface.
In doing so, Bakandritsos' team aims to produce handles for the immobilization of the bioreceptor on the platform, which he said are required for the effective and selective recognition of target analytes. "These ingredients, and other features of the materials and device architecture co-define the selectivity and sensitivity of the sensor," he said.
Another partner is Grenoble, France-based Grapheal, which produces graphene field effect transistor (GFET) sensors that can be used for multiplex biomarker analysis. These are produced using printed electronics in a compact design. During the COVID-19 pandemic, Grapheal launched an antigen test called TestNpass based on its technology.
The Catalan Institute of Nanoscience and Nanotechnology (ICN2) is also a technology partner. The institute specializes in electrochemical biosensing and graphene laser scribing techniques, and for 2D-BioPAD, it is developing an electrochemical sensor based on its print and stamp technology. This will allow for the production of the sensor’s graphene electrodes on paper.
"2D-BioPAD aims to explore both electrochemical and GFET sensors, targeting Alzheimer’s biomarkers," noted Bakandritsos. "The main difference between electrochemical and FET biosensors lies in their manufacturing strategy and in the mechanisms by which they detect biological interactions and transduce signals into measurable outputs."
"These are different technologies but have the same envisioned outcome," Tsolakis underscored. "We want to benchmark them together to see which one performs better, under real-world clinical conditions."
Both biosensors will host aptamers that are short pieces of DNA displaying recognition properties similar to that of antibodies but that offer multiple advantages with respect to their identification and their production, Tsolakis said. Novaptech, a Bordeaux, France-based company, will lead the selection and characterization of aptamers to AD biomarkers.
Τo further improve with flow control and sample purification and to avoid nonspecific signals, the Aristotle University of Thessaloniki (AUTh), a Greek technology partner, is synthesizing two-phase magnetic nanostructures that can conjugate with these aptamers to "raise the overall sensitivity, specificity, and reliability of the graphene-based biosensors," Tsolakis said.
There is also an artificial intelligence component to the project. CeADAR, Ireland's Center for AI, will employ AI to support the design of the aptamer probes on the device, so that they best target the biomarkers of interest. AI will also be used to improve the design of the graphene biosensor, Tsolakis said. In this way, 2D-BioPAD will be able to create more structurally robust graphene-based devices and sensors. "We will be using AI for material sciences," he noted, "which is a rather novel domain."
The tests will initially be assessed via clinical pilot studies at three institutions: the University of Eastern Finland in Kuopio; the Central Institute of Mental Health in Mannheim, Germany; and the Greek Association of Alzheimer’s Disease and Related Disorders in Thessaloniki. Tsolakis said that the studies are at the phase of having their protocols being approved by ethics committees and would start next year. They will involve up to 300 subjects, about 100 per country.
Tsolakis highlighted that the consortium format was best positioned to deliver such tests to market, noting that the skill set within 2D-BioPAD would be difficult for any individual team at a university or company to offer.
"We have people doing research on the core technology, industrial partners that can scale it up and move it to market, and regulatory, business, and clinical expertise within the consortium," he said. "This is not something that could make it to the market unless you were talking about a huge industrial player, like a big pharmaceutical company, for example."
Identifying markers for the early-stage detection of AD, as well as creating blood-based tests around them, is an area of interest for many researchers and companies, though. This month, the Alzheimer's Drug Discovery Foundation invested $7 million in C2N Diagnostics, a St. Louis, Missouri-based provider of blood tests for AD. Eisai, a Japanese pharmaceutical company, invested $15 million in C2N earlier this year. In recent months, both Roche and Beckman Coulter licensed AlzPath's pTau217 marker for use in future blood-based tests.
2D-BioPAD's own commercialization avenue, including where the test will launch and how much it would cost, is yet to be decided, and any decisions will be made later on in the project. For its part, Q-Plan will liaise with all the partners to determine how they would like to exploit the project's results. Evnia, a Danish firm that assists medical and in vitro diagnostics manufacturers with gaining regulatory compliance, is also taking part in 2D-BioPAD. Tsolakis said Evnia would assist the consortium in determining the best regulatory path forward.
"Of course, the European market is quite important and relevant for our project," he added.
By September 2027, he noted, 2D-BioPAD would like to have at least one prototype ready that has been vetted and validated by clinicians and healthcare professionals and to see that the clinicians have found the use of the consortium's devices to be valuable in real-life clinical practice.