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Lensless label-free nanoscopy

Project description

Big news for viewing tiny cells

Viewing cells at the nanoscale has traditionally required tiny fields of view and fluorescent labels, restricting insights into complex biological processes. Capturing large-scale, high-resolution images of live cells remains a major challenge. The ERC-funded NaNoLens project aims to develop a compact, label-free approach that reconstructs full-field holograms. Specifically, it will pioneer deep-UV lensless holotomographic nanoscopy. With an optics-free design, advanced algorithms, and full-angle tomography, NaNoLens can capture ten-gigapixel images, resolving individual extracellular vesicles across large cell cultures. These tiny spheres, key to disease diagnostics and drug delivery, can now be tracked in real time. The project is opening a new era of large-scale, high-resolution cellular imaging.

Objective

Optical nanoscopy has changed the “seeing is believing” paradigm. This was achieved within a limited field of view (FOV~100µm2) and required fluorescent markers. Large-FOV high-throughput live unimpaired cell imaging is crucial for biology and biomedicine. Hence, improving the space bandwidth product (SBP) using time-consuming scanning stitching is not a good solution. Lensless holographic microscopy (LHM) inherently bypasses FOV limitations by using full sensor-size hologram reconstruction for label-free object information retrieval. Its major limitation, not yet addressed, is its low lateral (~1µm) and axial (~3µm) resolution. I will overcome this fundamental problem by pioneering deep UV (DUV) lensless holotomographic nanoscopy (LHN) as a simple and compact device easily operated inside the cell chamber or outside the laboratory (in contrast to lens-based systems). Owing to DNA damage, DUV is used to sterilize and never image bio-samples. This paradigm will be shifted to provide a breakthrough 10 giga pixel SBP via a low-dose DUV optical-elements-free (no cost, no radiation loss) lensless setup with a worlds-first full-angle tomographic scenario, numerical aperture > 1, and a new class of reconstruction algorithms to decrease the effective pixel (to 100 nm) and remove background noise. I will use LHN to enable the discovery of a new mechanistic understanding of extracellular vesicles expression and intake within large live cell cultures with single-vesicle resolution. EVs, nanosized lipid spheres released by virtually every cell type, are currently emerging as novel disease biomarkers and drug nanovehicles. LHN is a new research field that inherently makes this a high-risk project, but the potential gains are also high as a new era of simple ultrahigh SBP nanoimaging might be opened. The proposed multidisciplinary project calls for near-unique expertise in computational microscopy and digital holography, which I acquired in cooperation with international leaders.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2023-STG

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Host institution

POLITECHNIKA WARSZAWSKA
Net EU contribution
€ 1 500 000,00
Address
PLAC POLITECHNIKI 1
00-661 Warszawa
Poland
Region
Makroregion województwo mazowieckie Warszawski stołeczny Miasto Warszawa
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)