Expansion Pathology

Ed Boyden: So for hundreds of years, the way you imaged biological things is you would take a piece of glass called a lens, and it would magnify the rays of light from a specimen. And that way you could see bacteria or brain cells or cancer cells or so fourth. But there’s a problem. Light has sort of a finite size of wavelength and there are certain things you just can’t see. Typically you can only see them with the electron microscopy but that’s expensive and painstaking and slow. So in our group we’ve been pioneering a strategy which does the opposite. Rather than zoom in, we blow things up. We’ll take a specimen, like a piece of brain tissue or some cells, infuse them with a chemical and then when you add water, the polymer swells and blows the specimen up. And that way you can physically magnify objects and see things with incredibly fine scale. So if you look at modern medicine, problems of the brain or the immune system or of a cancer, these are problems of large scale body systems and so you have to map out what’s happening in order to understand them and develop better treatments. Yongxin Zhao: So today we will demonstrate technology called expansion pathology. It’s a procedure that enables us to enlarge various kinds of clinical samples for optical imaging. So the first step we will pre-treat the various kinds of clinical specimens so they are ready for expansion. In the second step, we color some protein of interest in the tissues. Then we apply small chemicals to further modify the tissue so that the molecules in the tissues will be attached to the gel network that we synthesize in the later step/ And finally, we apply the treated tissue gel hybrid in pure water, and eventually this hybrid will expand several times in all 3 dimensions. Then we will take the expanded samples under the microscope for imaging. Octavian Bucur: By using physical tissue expansion, and looking at the samples with a conventional optical microscope, we can increase the resolution of the images so we can see fine features at the nano scale level that were not available before. Such examples are in kidney diseases. On the right side the image has much better resolution compared with the left side. In order to diagnos kidney disease we need to identify and investigate certain fine structures. These fine structures look like finger like projections. So compared with normal kidney tissue these spaces, Minimal Change Disease has these processes modified and the spaces, they almost completely disappear or are very irregular. So first time when I heard about this idea it was hard to believe. By physically expanding the tissue, we can diagnose these diseases. Ed Boyden: If you look at all sorts of diseases of the brain, of you know, cancers, of the immune system, they start out with very subtle changes. They develop sometimes over many years and in order to understand really what is the nature of a disease you have to be able to image the building blocks of those cells and tissues with nanoscale precision. So our hope is that expansion pathology will someday have impact on all sorts of different disease analysis, both for diagnosis – can we help a specific person, as well as developing new treatments. Can we come up with new ideas that can help all sorts of patients?

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