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Cutting-edge High Throughput Nanoscopy: the future of imaging is here

Periodic Reporting for period 1 - HT-SAFe (Cutting-edge High Throughput Nanoscopy: the future of imaging is here)

Reporting period: 2020-05-01 to 2021-04-30

Nanoscopy (or single-molecule-localization-microscopy) has developed rapidly in the past 10 years, revolutionising optical imaging (microscopy), bringing new knowledge and facilitating new discoveries in cell biology. Nanoscopy breaks the diffraction limit, the previously impenetrable physical barrier that restricts the optical resolution of a microscope to 250 nanometers (nm) and achieves unprecedented resolutions of 5-10 nm. Thus, thanks to nanoscopy, for the first time today it is possible to see how sub-cellular molecular machineries form and behave inside single cells2 and to characterise and quantify single biological molecules such as proteins, nucleic acids, lipids, at ultra-low concentrations inside the cell.

For the first time since Nobel price 2014 was awarding nanoscopy invention, Abbelight has provided to researchers the most complete and reliable nanoscopy solution on the market with the best imaging resolution; nonetheless, a majority of users also need higher throughput to unravel and understand rare biological events, such as those behind the varying responses to treatment of cancer cells, the challenge of personalized medicine.

However, a Hight-Throughput imaging system with nano-resolution does not exist yet.

That is why Abbelight is moving much further into the highly challenging development of the new HT-SAFeTM platform: the first connected and automated high-throughput / high-content (HT/HC) nanoscope platform. It will fill the gap between existing nanoscopes and existing HT/HC classical microscopes and truly transform the market, improving dramatically research in (cell) biology and enabling discoveries at unprecedented speed and resolution.
During the first period, the main goal was to increase the throughput of our nanoscopes. In that perspective we have first increased drastically the throughput by a factor ~200 thanks to new optical excitation and detection strategies.

On the excitation side, we have developed ASTER (A. Mau et al., In press, Nat. Comm. 2021) that is an hybrid widefield and scanning illumination method. Thanks to that innovation, we are able to cover in one shot a sample area ~64 times larger than the standard of the market (200 x 200 um² compared to 25 x 25 um²). A faster implementation is on going to cover up to 325 x 325 um² (170 times larger throughput). Another important aspect of this new method is it abality to offer reliable data, a key important value for high-throughput imaging and its relative market, the pharmacology. ASTER has been integrated in all abbelight imaging product and it is therefore distributed all around the world via abbelight sales teams and distributors. This method is also under publication at a prestigious journal, Nature Communication (should be released in June 2021).

On the detection side, we have developed a new strategy that offers reliable multi-species imaging (generally named multi-color imaging) without any optical drawbacks. Thanks to this strategy, called spectral demixing, we are now able to image simultaneously up to 3-colors (3 biological species of the same cell) whereas it was generally main limited to 1 color. Therefore, this strategy also improves the throughput by a factor 3 and combined with ASTER excitation method, we have now improved the throughput of our nanoscopy by a factor ~200 times. As ASTER, spectral demixing detection is already implementing on our SAFe 360 instrument and a new dedicated product was developed : the SAFe redSTORM.
Our developments during 2020 lead to a first generation of high throughput nanoscopy instruments. This huge improvement in throughput will greatly help the uptake of the pharmacology and clinical diagnosis market with nanoscopy instruments and opens the way to new application, with a very important societal impact (Billons of dollars market).
New nanoscopy product with 200 times larger throughput