Nanoscale Digital Microscope

Project Information

NanoXim

Grant agreement ID: 946105

DOI

10.3030/946105

Project closed

EC signature date 26 May 2020

Start date 1 November 2020

End date 30 April 2022

Funded under

• EXCELLENT SCIENCE - Future and Emerging Technologies (FET)

Total cost

€ 100 000,00

EU contribution

€ 100 000,00

Coordinated by

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
France

Periodic Reporting for period 1 - NanoXim (Nanoscale Digital Microscope)

Reporting period: 2020-11-01 to 2022-04-30

Summary of the context and overall objectives of the project

The NanoXim project proposes a disruptive nanoscale holographic microscope with a sensing architecture that can compensate for the lack of complexity of usual optical components (confocal) or markers (fluorescent) by using novel theories and numerical algorithms. The technique based on digital holography allows realizing 3D movies with μm-scale resolution. The instrument developed at CEA builds phase contrast maps of a specimen by using 3D propagation and numerical reconstruction algorithms already implemented in a user-friendly interface. We propose to realize a study of a large panel of end-users and to validate immediate needs and requirements in health problems and bio-technology. The first objective consists in supporting CEA to bridge the gap from research prototypes to the pre-commercial products, thus increasing the technology readiness of the instrument. TEMATYS SME will support this by bringing a market analysis and set a full business model. We will seek for valorization through patenting and licensing to put the instrument close to the market. All this will allow us to evaluate the opportunities and feasibility of the creation of a startup to bring our new microscope to the market.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The NanoXim microscope is an in-line digital holographic microscope, which leads to a very compact, simple and easy to use device. Using an iterative algorithm and numerical back propagation to retrieve the sample image at any plan from a single hologram, it reaches 1.38 μm lateral spatial resolution with a depth resolution of the order of 5 µm. The typical acquisition time, depending on the sample, ranges between 30 and 100 ms, enabling very fast real time acquisitions. Moreover, it does not require the use of biomarkers to enhance the features under study. Several high end users were contacted and had the opportunity to trial the NanoXim in a real laboratory environment on their own samples. Their feedbacks point out the same advantages of the NanoXim microscope with respect to the other imaging tools they usually use (fluorescence microscopy, light sheet microscopy). The large field of view (approx. 4mm² for the current prototype) associated with a good spatial resolution and short integration times allows gaining in the speed of the experiment, screening many samples simultaneously. Another asset is the NanoXim 3D imaging capability that requires only a single acquisition. Again, this allows fast 4D acquisition. Finally, the ease of use is clearly another advantage of the prototype. While using iterative algorithms to reconstruct the sample image, it does not require any specific computer.
In the meantime, a global market analysis put in evidence two segments to target, i.e. 3D cell cultures and small animal model imaging. The digital holograms produced by the technology lead to a very large possibility of post-treatment without any loss of data. One key axis of development will be in the software development of bioinformatics modules, such as retrieval of 3D features, live tracking of whole cell/features, automation protocols… Three kinds of hardware products have been identified: simple microscope, with most revenues generated by licensing of analysis software, 4D large sample analysis and 4D biological monitoring, which would however require an increase of the spatial resolution to compete with other technologies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the recent years, biotechnology and biology have experienced an increase in the number of instruments and equipment needed to explore living mechanisms at the gene, protein and even nanoscale levels. However, the microscopy market in life sciences - around 4,8 B€ worldwide – has to propose new solutions and adequate tools for systems biology. New modalities are developed in 2 directions, high-resolution devices and large field of view devices. The global market for the latter, of interest to study the metabolism of organisms in 4D, is estimated at around 290 000 units p.y. gathering a strong diversity from incumbent products to emerging ones. While lensless microscopes represent still less than 1% of total market value, their low-price and ease of use could allow them a strong diffusion in the market. Indeed, the CAGR in the large-field-of-view segment is very low for low-end and mature products (binocular, macroscopes), it is up to 25% for emerging modalities.

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