how then-Thiel/Musk-funded company Halcyon Molecular was stretching out DNA molecules using a mechanical probe and arraying them precisely on surfaces. Discussing with @geochurch, however, he pointed out that, apart from my lack of talent in building AFMs,
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this was super un-scalable in principle, and that instead, to make chip-scale nano-assemblies, one should obviously use *optical* patterning of DNA to uniquely define mesoscale locations on a surface, and then make the nano-precise DNA nanostructures *big* enough that they could
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bridge between the optically-defined spots. So I spent a year or so trying to make DNA nanostructures big enough to achieve that size-match with the big (>micron) patches of DNA that could be defined optically according to this so-called "nanometer to centimeter" or nm2cm scheme.
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This was very interesting, and taught me a lot, but ultimately I failed to make good enough giant nanostructures to support the "nanometer to centimeter" scheme that Church and I had envisioned. Some years later, however, I was in the business of thinking up schemes for scalable
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brain circuit mapping with the amazing
@eboyden3 and his brilliant and adventurous graduate students like@SGRodriques, as well as a few of the graduate-student-like entities floating around the Media Lab, notably the young artist Dan Oran who was an expert on the chemistry1 reply 0 retweets 1 likeShow this thread -
behind classical non-digital photography as well as holograms and things like that. In that context, it turned out that being able to *change the sizes* of supra-molecular assemblies was becoming quite important, as in Expansion Microscopy one chemically links the molecules
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of interest in a brain sample into a hydrogel, and then swells the hydrogel to move those molecules apart from each other, to make them easier to see optically and more chemically accessible to biochemically interrogate/sequence/decode. What this unexpectedly opened up, though,
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was the possibility of running expansion microscopy in reverse! If one could do that, one could create optically-defined spots (in 3D) for attaching materials, and then shrink these spots down to a level where they become usefully nanoscale (e.g., for optical meta-materials
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applications where you want structures smaller than the wavelength of light). Thus, connecting back to the lineage of thinking around the nm2cm project, rather than than trying to make *bigger* building blocks to cover or bridge between optically defined spots, one could instead
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make the spots themselves *smaller*. So that is, in essence, what this paper does -- it optically patterns a hydrogel, then shrinks the resulting pattern. Now, nanotechnology still has a very very long way to go, particularly I think in accessing the length-scales of covalent
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chemistry, which are even smaller than the few nanometer minimum feature size on a DNA origami... an orthogonal but perhaps even more important problem compared to the mesoscale assembly problem that we tackle here. Moreover, extending ImpFab to create economically useful
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devices at scale, and perhaps, if it proves useful, to the kinds of integrated nm2cm DNA templated assemblies
@geochurch and I envisioned, requires several further major steps. But I'm happy to look back on how a number of serendipitous intersections of people and technologies,1 reply 0 retweets 1 likeShow this thread -
and amazing work in the lab and on the whiteboard by Dan and Sam and the other co-authors, has led to an early milestone with this publication. Thanks to all the supporters of convergent technology involved this this work! /end
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