About the sample preparation techniques I described in an earlier post, Paul Rothemund writes to say
Those picture are neat; as far as I know, no one has done freeze fracture / freeze-etch electron microscopy [of DNA nanostructures]. That is a gap, certainly….
A study of the effects of critical point drying or freeze drying/sublimation on DNA nanostructures is high on my list for techniques we need to get worked out for incorporating DNA nanostructures into devices. It is very simple and yet someone in the field has just got to spend 6 months figuring out what the right protocol is…. I think it is just going to work and will give us great preservation of structure without the artifacts of dewetting from fluid.
In short: This is an important problem (helping SDN researchers see what they’re doing), and solving it can help solve an even more important problem (making dry composite nanosystems from wet DNA nanostructures). Paul thinks that someone with the right facilities could adapt known methods to solve this problem rather quickly, and I agree. We’ll see who gets there first.
[Updates]
But what about citations?
I should perhaps mention that, according to a study of “Citation Classics” [pdf],
…methods papers…tend to make strong showings in these lists of highly cited papers. The papers in this group demonstrate the importance of methodology and technology in propelling scientific research….
[Update] Paul suggests that I add a link to the first post in this mini-series, “A DNA-Imaging Bottleneck”, which pointed to the scarcity of facilities for cryo-electron microscopy and (tomography in particular) as a motivation for looking at these other techniques.
[Update x 2] Regarding the technique itself, relatively shallow etching to partially uncover a structure — producing just “bas-relief” images of multiple surfaces — would tell a lot about its geometry (compare images C and E here). This should be straightforward, with no delicate requirements, and I eagerly await some images.
