A novel lab-on-a-chip platform for studying tissue metabolism in situ
Tissues encompass a range of different cell types in a highly organised structure to attain function. Understanding the processes that govern the interaction of cells at the tissue level cannot be achieved by studying individual cells in vitro. At the same time, the three principles of replacement, reduction, and refinement with respect to animal testing demand an alternative framework for conducting research.
Combining organ-on-chip and NMR technologies
The EU-funded TISuMR project generated a new technological platform that allows for the direct biochemical characterisation of tissues cultured in microfluidic devices in vitro. These offer a powerful way to model entire organs with applications in diagnostics and biomedical research. The multidisciplinary background of the TISuMR team was instrumental in successfully combining nuclear magnetic resonance (NMR) spectroscopy with the culture of tissue slices in a miniaturised lab-on-a-chip. NMR spectroscopy is a non-invasive, high resolution spectroscopic technique that allows the characterisation of a sample at the molecular level. It is ideal for observing metabolic, biological, and chemical processes of living systems due to its non-invasive nature. “Our goal was to overcome the limited sensitivity of NMR spectroscopy and combine it with our microfluidic culture system for observing tissue metabolism,” explains Marcel Utz, project coordinator and professor at the University of Southampton.
Challenges and applications
NMR spectroscopy requires the sample to be placed into a very large magnetic field, which must have the same strength over the entire sample. Combining this with the strict conditions needed to keep tissues healthy over an extended period outside of the body posed great technical challenges. Researchers overcame these with an original design that leverages existing high-performance magnetic resonance spectrometers, available in many laboratories both in academia and in industry. “Our platform goes far beyond what was previously possible, offering unprecedented detail and accuracy on tissue metabolism,” emphasises Utz. The TISuMR platform was successfully employed to explore cholestasis – a phenomenon associated with the obstruction of bile flow, often caused as a side effect of many important drugs, which prevents their effective use. The TISuMR system provided crucial information on the changes in liver metabolism caused by cholestasis, offering important insight towards the design of new drug candidates that avoid this side effect.
TISuMR technology prospects
The most significant impact of the TISuMR new experimental approach is the generation of rich data on the biochemistry of the tissue, without interference. This can be applied in other tissues such as the lung, heart and kidneys. Through hyperpolarisation techniques, it may be possible to further enhance NMR signals and obtain even more detailed information. “We anticipate that the technology developed through TISuMR will find many applications such as drug development and cancer research,” concludes Utz. Partners continue to work towards making the technology available to others through spin-off companies, such as Voxalytic GmbH, Germany and microVita in the United Kingdom. Further optimisation of the technology will tailor it to user needs. In parallel to these commercialisation efforts, partners aim to further enhance the capabilities of the TISuMR technology, for example by incorporating information on the physiology of the tissue, or by extending applications to cancer biology.
Keywords
TISuMR, NMR spectroscopy, microfluidic, tissue metabolism, tissue slice, drug, lab on-a-chip, cholestasis, hyperpolarisation, nuclear magnetic resonance
