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HEIndividual fellowship2023–2024

EXO-CHIP · Nanofluidics for label-free detection of exosomes and protein aggregates in neurodegenerative disease research

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-01-01 → 2024-12-31
EU contribution
€210,911
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

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Results in brief

Nanofluidics for label-free detection of exosomes and protein aggregates in neurodegenerative disease research

The capability to observe single molecules is key for finding new tools in the complex space of biology and physics as our society strives for next-generation health diagnostics, intends to combat neurodegenerative diseases in an ageing population and wishes to improve medical treatment for cancer patients in hospitals. EXO-CHIP's aim was to develop nanofluidic mass producible chips for the analysis of biomarkers - e.g. Extracellular vesicles (small round particles circulating in human blood) or neurodegenerative protein aggregates e.g. Alpha-synuclein ( a protein affiliated with the development of Parkinson's and Alzheimer's disease).As these specimen are rather small (EVs = 40-120nm, A-syn=3-10nm) they are hard to detect with current assays without the use of chemistry to fluorescently label them. This chemical labelling can induce changes in the specimen and alter its biophysical behaviour - ultimately biasing any assay conducted on these so far. Therefore we have tremendeous need and motivation to develop label-free methods (preferentially optical methods) to observe their assembly and size without altering their physiological behaviour. Awareness of this bias is crucial for interpretation and criticism towards developments made in the field and policies in place for treatment of these disease but also legislation of drugs to treat those. EXO-CHIP's objectives are (i) to train the grant recipient in the scientific disciplines needed, for (ii) the development of nanofluidic chips and the combination with two label-free microscopy techniques (iii) Quantitative phase microscopy (QPM) and (iv) deep-ultra-violet microscopy (DUVM). Expected impact of successful developments during the action are: (i) a new method and scalable device for improved healthcare, (ii) reduction of precious biomaterial for development of next generation treatment of neurodegenerative diseases at (iii) reduced economic costs due to savings in material and time for hit-generation in the development of medicines.

Data: CORDIS, © European Union

Project objective

Microfluidics have become a powerful tool in biotechnology and life sciences, whereas the nanofluidic regime remains widely unused in industry and the clinical environment. Especially protein misfolding diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease, recently experience a growing demand for single-molecule detection capabilities, as the assembly process of a single corrupted protein is correlated with its aggregation propensity and spread of the disease. Conventional microfluidic methods to study relevant biomarkers and aggregates involve fluorescent labelling, which alters the samples' properties and puts additional constraints on experimental design. We therefore seek for methods to study macromolecules (in particular: exosomes, oligomers) in a label-free manner in solution without chemically altering their properties.To overcome this limitation, the project combines innovative nanofluidic technology with cutting-edge label-free microscopy techniques. First, hybrid 2-photon lithography is used for the scalable cost-effective nanofabrication of nanofluidic polymer chips. Secondly, these chips are then employed for the detection and sizing of exosomes (<100 nm) and alpha-synuclein protein aggregates (<12 nm) in solution using label-free imaging methods (e.g. QPM and DUVM).The approach presented here, allows protein misfolding researchers to study oligomerization more efficiently by running orders of magnitude more experiments with same already limited material, and greatly increases availability of nanofluidic chips for protein metrology in existing biological laboratories. New expertise, excellence, management skills and scientific training acquired during the action, prepare the researcher for a role as independent dementia research group leader in Europe, using state-of-the-art nanotechnology to establish nanofluidic single-molecule detection of protein aggregates and macromolecules as new golden golden standard in life sciences research.

Original text from CORDIS.

Participants

  • UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET · TromsoCoordinatorNorway

Links

Data: CORDIS, © European Union