Technology Readiness Level: 4
*As assessed with the Human Brain Project's TRL Guide
Technology Description
We have devised a complete pipeline of light-sheet microscopy, encompassing sample clearing and staining, fully automated high-resolution high-speed imaging, and teravoxel image processing. The microscopy pipeline makes it possible to analyse macroscopic tissue samples at sub-cellular resolution. Our system has two fundamental advantages: first, imaging quality is always kept high thanks to automated feedback systems for light-sheet stabilization and autofocusing. Second, a dedicated set of software tools enables management and effective access to teravoxel-sized images, allowing subsequent data analysis.
Competitors do not provide any active stabilization of the light sheet, requiring continuous adjustment of imaging parameters by the user. Neither do they provide links between the imaging system and image analysis tools.
Tight interconnection between the imaging system and image analysis tools ENABLES effective management of teravoxel-sized imaging datasets
Fully automated microscopy enables scalable 3D analysis of biological tissues for research and clinical purposes
Competitive Advantages
High-resolution, fast, fully automated 3D imaging of tissue samples
Few hours needed to process 1cm3 with 1μm3 resolution
Patented feedback solutions
for real-time stabilization of the light sheet and autofocusing
User support
for processing of raw data, not as with current commercial solutions
Scalable volumetric analysis
of multiple tissue samples
Applications and Market Potential
Preclinical research: quantitative and reliable quantification of drug effects at whole-organ scale
Histopathological analysis of human tissue for augmented diagnostic & prognostic power
Personalised medicine: improved assessment of drug efficacy on patient-derived organoids
Worldwide optical microscopy market in 2018 is about $2 billion; histopathology market about $4 bn
WITH THE RAPID TECHNOLOGY...
1. RAPID overcomes limitations of current autofocus systems for microscopy
2. RAPID provides real-time operation without any reference reflection
3. A single solution can be used for all wide-field microscopes
1. We devised a new method for focus stabilization in optical microscopy. Standard methods rely either on contrast optimization (thus working offline) or on triangulation (requiring a reflective surface).
2. RAPID (Rapid Autofocus via Pupil-split Image phase Detection) extends to the entire field of view of the instrument the phase-detection principle, which is limited to selected points of interest in professional photography.
3. This method allows direct evaluation of the defocusing state of the system simply using the detected image. Therefore, RAPID is completely agnostic with respect to sample or microscope, and can be applied to all systems, in all settings.
Interesting Facts
- High-throughput automated light-sheet microscope used within Human Brain Project and the NIH BRAIN Initiative
- Top-tier published papers (Silvestri et al., Nature Methods 2021)
- Collaboration with the University of Florence and the Italian National Research Council
- Registered Patent WO2018122093A1
The LENS facility hub offers access to two microscopy setups capable of high-speed and high-resolution imaging with simultaneous two-colour acquisition.
More info here
