Slide scanning microscope for high-throughput tissue imaging

Understanding the structure and organisation of complex organs within the body, for example the brain, requires the ability to see the intricate components that make up that organ and measure where they are located and how they function. To understand the biology of disease we compare healthy people and those with the disease, to determine what has changed in the organs of those who are ill. Many diseases and disorders are highly complex, meaning they can have multiple causes and patients can display a wide variety of symptoms. Understanding this complexity requires the ability to image at scales that allow for meaningful comparisons within and across samples, typically needing many 100s of individual samples to be studied. Funding will allow the acquisition of a new microscope that has the capability to rapidly image from a very large number of samples. This microscope is motorised and fully automated, meaning it can run through the samples at high speed, producing large datasets with relatively few man hours of researcher time spent. The microscope also has the ability to detect the presence of multiple different fluorescent markers, which are used to stain the tissue to highlight key structures or cell types within the sample.

The microscope will be housed within a state-of-the-art bioimaging facility at the University of Bristol, which allows access for over 400 researchers. Researchers will use this new microscope to gain deeper insight into a wide range of diseases, including immune dysfunction, arthritis and cardiovascular disease, as well as mental health disorders spanning depression, schizophrenia, autism and chronic pain.

Advances in our ability to label and manipulate tissues within the body have been hugely transformative in our understanding of biology. Typically, analysis is performed over a small sub-sample of the tissue of interest, with a large amount of tissue going to waste due to the inability to reliably and rapidly image or analyse it. This occurs because, particularly with transgenic tissues expressing various fluorescent proteins, the native fluorescence used to label the samples fades over time. The ability to rapidly image and archive tissue would therefore be hugely advantageous, as it would create a digital repository that would allow researchers to expand the scope of their existing research and develop novel hypotheses. This capability to scan through many sections of tissue is particularly relevant in studies of non-homogenous tissues, such as the brain, where each section of tissue labels distinct structures whose contribution to health and disease may not have been fully elucidated. Understanding the connectivity of the brain also requires whole brain analysis, which is only possible by analysing a large number of tissue sections.

Funding for a slide-scanning microscope will support a wide array or researchers spanning neuroscience, cardiovascular disease, renal medicine and stem cell research. Using this new microscope researchers will be able to utilise the flexibility of the system and its high throughput imaging capability to perform an array of exciting projects, from understanding changes in the structure and circuitry of the brain in neurodevelopmental and neurodegenerative disorders, deciphering disease-related changes in the heart and kidneys and developing novel stem-cell regenerative therapies to potentially treat such disorders. Our multi-disciplinary team are experts in the necessary techniques to complete these studies and so are ideally placed to apply this microscope to a range of exciting projects.