Friday, January 16, 2026

Breaking the resolution limit of light microscopy

image credit: HHMI
Here's a photo of the original PALM microscope in the living room where it was developed, and a story about this and related technologies. The Wikipedia page on super-resolution microscopy discusses PALM and several other tricks for breaking the limit of resolution for light microscopy, and this article is a nice description of the challenges and multiple clever solutions to improving resolution beyond the usual limit.

source

"...that’s where we learned about photoactivatable fluorescent proteins.... it became obvious to Harald and me that this was the missing link for the idea that I had pitched after I left Bell: we could isolate a few molecules at a time by activating limited subsets of photoactivatable proteins. It seemed so easy."

"...We were both unemployed, but Harald had some of his equipment from Bell [Labs]..."

-from Betzig's Nobel speech

Xiaowei Zhuang's lab developed a similar method, called STORM, around the same time as PALM was developed. See "STORM image gallery" at her lab web site for some super-resolution images.