Development of SPIM technology

The invention of single plane illumination microscopy (SPIM) technology started in Ernst Stelzer’s lab at EMBL in the early 2000s.

SPIM allows minimally invasive 3D imaging of multicellular specimens at high resolution and has many applications, such as modelling tissue development and disease progression. Almost two decades on, the Stelzer lab at EMBL developed a fluorescence SPIM microscope that allowed scientists for the first time to watch a living embryo develop at the cellular level. The SPIM technology was further developed by Lars Hufnagel, a former group leader in the Cell Biology and Biophysics Unit at EMBL, so that larger samples could be studied at high resolution. Hufnagel described the key advance in a Nature Methods paper, which was later recognised by Nature as Method of the Year 2014. The development of this new technology sparked a lot of interest from the research community:
"We were contacted by a number of labs that wanted to get access to this disruptive technology," said Jürgen Bauer, EMBLEM's deputy managing director.

The demand for SPIM technology inspired EMBLEM to create the company Luxendo to make the technology widely available to the scientific community.

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Keller’s digital zebrafish – the first complete developmental blueprint of a vertebrate. Credit: Keller et al./EMBL

Scaling up SPIM for the scientific community

Luxendo was founded in 2015 to commercialise the novel microscopy technique. The start-up, which is based at EMBL Heidelberg, benefited from both external investment and internal scientific expertise and access to EMBL users, who provided feedback on prototypes and early versions of commercial products. In October 2015, Luxendo raised €8 million in venture capital funding from EMBL Ventures and Life Science Partners to further scale and commercialise SPIM microscopes. The rapid success of the company increased the need to find an external partner to help with the distribution channel and increase Luxendo's international presence. In 2017, Bruker (a USA-headquartered public limited company manufacturing a wide range of scientific instruments for health and life sciences applications) acquired Luxendo with a valuation of €17 million.

Hufnagel joined Bruker as Vice President and General Manager of Luxendo to take the "brainpower from EMBL to Bruker" and continue innovating the technology. He has since developed several new SPIM products and has kept the EMBL tradition of fostering an open science:

We play an active role in supporting the open-source community by integrating and maintaining data processing tools.

This declaration reflects the willingness of the private instrumentation sector to support a hybrid distribution model, where private companies sell their products at commercial rates while making software and tools openly available.

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In a symphony of colours, this light-sheet microscopy image shows how zebrafish embryos start developing. The pale rings circling the embryos serve as contractile belts, allowing the spherical embryos to change shape and take the next developmental step. Credit: Krisztina Arató, Gopi Shah/EMBL

What the future holds

As a result, EMBL's SPIM technology has come into widespread scientific use, and EMBL has been able to invest the proceeds from the trade sale into the launch and early-stage funding of several other EMBL spin-offs. This strategy has resulted in several other successful spin-offs. Through Bruker, SPIM microscopes are now available in more than 100 laboratories worldwide (including across the USA, Europe, and Asia). Most customers (90%) are based at research universities or institutions and work in one of several application areas (such as biology, stem cells, brain neuroscience, and clear tissue).

Over the past two years, however, this technology has been also requested more frequently by contract research organisations and pharmaceutical companies. Most recently, Memorial Sloan Kettering Cancer Center (MSKCC) in New York City has purchased SPIM microscopes from Bruker to visualise how cancer cells develop, with the aim of discovering new cancer treatments. "Instruments such as these [SPIM microscopes] are useful for imaging cancer cells and processes that enable [them to spread]," explained Anna-Katerina Hadjantonakis, Chair of the Developmental Biology Program, at MSKCC.

EMBL’s experimental services deliver substantial value to Europe by delivering scientific services and thereby enabling researchers to conduct novel and demanding experiments that could not be easily achieved at a purely national level, an independent review found.

The global consultancy Technopolis Group, specialising in research and innovation policy, conducted a survey and analysis of external (non-EMBL) users of EMBL’s experimental services. The survey aimed to identify whether users perceived scientific, technological, societal and economic benefits as a result of utilising the experimental services at EMBL Barcelona, Grenoble, Hamburg, Heidelberg, and Rome.