HE ERC Proof of Concept Grant 2026-2028

BrightMind: An Integrated Hardware-Software Platform for Smart Photon Resolved Microscopy

Abstract: Fluorescence laser-scanning microscopy (LSM) is the workhorse of life-science research, enabling low-invasive methods to probe live-cells with molecular sensitivity and high spatiotemporal resolution. Its impact has recently been expanded by photon-resolved microscopy, which uses single-photon array detectors to record photons one-by-one with precise spatial, temporal and spectral signatures. Analysis of this dataset yields unprecedented information, such as sub-diffraction images (down to the molecular scale), functional images, insights into molecular dynamics, and estimates of the microscope optical aberrations. These advances promise new biological discoveries and a new era of smart microscopy, where photon-level information drives experiments in real-time – e.g., correcting aberrations with adaptive optics. Despite this potential, photon-resolved microscopy remains confined to expert labs. Data complexity, fragmented hardware and offline software hinder accessibility, while evolving detectors and (AI-based) analysis quickly outpace existing solutions. BrightMind is the first customisable, upgradable, and integrated hardware-software platform for photon-resolved LSM. Built on system-on-chip FPGA technology, it unifies photon time-tagging with on-board processing, instantly transforming photon streams into interpretable results. This integration makes possible what was once impractical: real-time feedback LSM, plug-and-play use with any LSM system, and flexibility to evolve with new detectors and algorithms. BrightMind provides standardised outputs – from photon streams to pre-processed histograms, from application-ready results to RGB video frames – supporting researchers, fostering innovation by developers, and easing integration for microscopy and photonic devices manufacturers. By lowering barriers and streamlining workflows, BrightMind positions photon-resolved microscopy as the next generation of LSM, paving the way to smart and information-rich microscopy.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Consolidator Grant 2019-2025

Multi-Parameter Live-Cell Observation of Biomolecular Processes with Single-Photon Detector Array

Abstract: Fluorescence single-molecule (SM) detection techniques have the potential to provide insights into the complex functions, structures and interactions of individual, specifically labelled biomolecules. However, current SM techniques work properly only when the biomolecule is observed in controlled environments, e.g., immobilized on a glass surface. Observation of biomolecular processes in living (multi)cellular environments – which is fundamental for sound biological conclusion – always comes with a price, such as invasiveness, limitations in the accessible information and constraints in the spatial and temporal scales. The overall objective of the BrightEyes project is to break the above limitations by creating a novel SM approach compatible with the state-of-the-art biomolecule-labelling protocols, able to track a biomolecule deep inside (multi)cellular environments – with temporal resolution in the microsecond scale, and with hundreds of micrometres tracking range – and simultaneously observe its structural changes, its nano- and micro-environments. Specifically, by exploring a novel single-photon detectors array, the BrightEyes project will implement an optical system, able to continuously (i) track in real-time the biomolecule of interest from which to decode its dynamics and interactions; (ii) measure the nano-environment fluorescence spectroscopy properties, such as lifetime, photon-pair correlation and intensity, from which to extract the biochemical properties of the nano-environment, the structural properties of the biomolecule – via SM-FRET and anti-bunching – and the interactions of the biomolecule with other biomolecular species – via STED-FCS; (iii) visualize the sub-cellular structures within the micro-environment with sub-diffraction spatial resolution – via STED and image scanning microscopy. This unique paradigm will enable unprecedented studies of biomolecular behaviours, interactions and self-organization at near-physiological conditions.

Total budget: 1.861.250,00€

Total contribution: 1.861.250,00€