The Stevens Group
The Stevens group is focusing on the development of techniques and technologies to monitor the functionality of the organoids on the chip and measure their changes upon drug treatment.
The group has extensive expertise in Raman spectroscopy based techniques. Raman spectroscopy is a non-destructive analysis technique that provides chemical and structural information. It can be applied to live cells and tissues. Stevens and co-workers previously developed a computational framework for 3D Raman imaging and analysis. They are now using it to assess healthy and steatotic (fatty liver disease) liver organoids. The accumulation of retinol, glycogen and lipids within liver organoids can be detected and quantified. In addition, the distribution of cytochrome C is visualized. The technology is being progressed for incorporation within the organ on a chip platform. Upon exposure to therapeutic compounds, 3D Raman analysis will be used to measure drug metabolism and assess the condition of liver organoids, thereby advancing the technology towards a drug-screening platform.
Furthermore, Stevens has recently published in Advanced Materials a technique for nanoscale volumetric bio-molecular mapping. This technique, called immuno-gold FIB-SEM, combines labelling of antigens with gold-conjugated antibodies with a slice-and-view electron microscopy technique. It provides simultaneous structural and bio-molecular information with high spatial resolution. This technique, correlated with 3D Raman imaging, has the potential to broaden the insight into cellular processes when organoids are interrogated with therapeutic tools.
Raman spectroscopy can also be used to develop label-free sensing systems. The Stevens group has recently published in Nature Communications an “artificial nose” that can distinguish the fingerprints of different cell lysates using label-free surface-enhanced Raman spectroscopy. It is based on plasmonic surfaces functionalized with mildly selective self-assembled monolayers. The interaction of biomolecules with each sensor generates a signature that allows the analysis and identification of complex biological matrices. The experience of the group with plasmonic sensors is currently being leveraged to design advanced biosensors for real-time monitoring on organ-on-a-chip platforms. Sensors that can detect and quantify in real-time specific biomarkers as they are produced by the cells are being developed.
In addition, the Stevens group is exploiting its expertise in printing techniques to pattern surfaces with a number of different activators/inhibitors of the WNT pathway via inkjet printing. Stevens is studying how these patterned substrates stimulate the cells and could guide the differentiation of induced pluripotent cells into functional organoids. Through the UK Regenerative Medicine Platform “Smart Acellular Materials Hub”, a 10 institutions research consortium directed by Stevens, the group has access to materials for further exploring 3D culture of organoids.
Finally, Stevens has been working with the Rayner group on setting up a Minio - node at Imperial College London. The Minio Platform will serve as a data warehouse with improved data access and management. In order to distribute the workload of the warehouse, a working node had to be set up at each university involved in the project. A new research data store of 20 TB has been allocated and a virtual machine has been set up by Imperial College ICT. This will facilitate collaborative efforts across the Centre.
- T. von Erlach, S. Bertazzo, M. A. Wozniak, C.-M. Horejs, S. A. Maynard, S. Attwood, B. K. Robinson, H. Autefage, C. Kallepitis, A. De Rio Hernandez, C. S. Chen, S. Goldoni, M. M. Stevens.“Cell geometry dependent changes in plasma membrane order direct stem cell signalling and fate.” Nature Materials. 2017. DOI: 10.1038/s41563-017-0014-0
- C. Kallepitis, M S. Bergholt, M. M. Mazo, V. Leonardo, S. C. Skaalure, S. A. Maynard, M. M. Stevens. Nature Communications. 2017. 8: 14843.“Quantitative volumetric Raman imaging of three dimensional cell cultures.”
- C. Chiappini, E. De Rosa, J. O. Martinez, X. W. Liu, J. Steele, M. M. Stevens, E. Tasciotti. “Biodegradable silicon nanoneedles for the intracellular delivery of nucleic acids induce localized in vivo neovascularization.” Nature Materials. 2015. 14: 532-539. [FRONT COVER] (Highlights in Nature Materials News and Views and IO9)
- P. D. Howes, R. Chandrawati, M. M. Stevens. “Colloidal nanoparticles as advanced biological sensors.” Science. 2014. 346: 53-63.
- S. Bertazzo, E. Gentleman, K. L. Cloyd, A. H. Chester, M. H. Yacoub and M. M. Stevens. “Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification.”Nature Materials. 2013. 12: 576-583. [Front Cover] (Highlights in C&EN and Materials 360)