Now the group has deployed ExM to help another field plagued by a reliance on complex machines to see tiny things: pathology, or the diagnosis of clinical disease using human tissue and blood samples.
Boyden and his team reported recently in Nature Biotechnology that they are using ExM to enlarge samples that aid disease diagnosis, a new technique they call “Expansion pathology”.
The technology expands samples by first infusing them with a soup of molecules, then chemically triggering the molecules to glom together in a polymer gel that clings to biomolecules within the samples.
Not only are expanded samples easier to see because they are larger and more transparent, fluorescent tags and other labels can also be added to track individual molecules of interest, including specific genes in the nuclei of cells-a feature electron microscopy lacks.
In order to prove their expansion technique works on human pathology samples, the research team’s biggest hurdle was working with the weird ways that researchers prepare tissues for diagnosis.
When seven observers were asked to analyze images of expanded, fluorescently labeled kidney podocytes, they correctly classified the samples as healthy or indicative of minimal change disease with 90 percent accuracy, compared with only 66 percent accuracy with unexpanded images.
“Super-resolution microscopy in general is expensive and time-consuming, and we don’t use it much for treating patients. Minimal change disease represents 1 percent of anatomic pathology diagnoses done today. So while ExPath is great for that condition, it’s not really clinically relevant yet. However, I look forward to reading many papers in the future that use this technology because I think it’s a better research tool than electron microscopy.”