MM breakthroughs needed
From Wise Nano
Claim: Molecular manufacturing is not waiting on any scientific breakthroughs.
There's no doubt that developing molecular manufacturing will require a lot of engineering and scientific research in a lot of fields. The question is whether this will be the kind of research you can schedule and pay for (R&D), or the kind you just have to wait for (scientific breakthrough). Edison's discovery of a practical electric light bulb took immense amounts of R&D work (from the Humphry Davy 1809 carbon filament through the Warren De la Rue platinum filament in vacuum in 1820 to Edison's testing thousands of materials for the filament before ultimately settling on carbonized bamboo in 1888), but was not a scientific breakthrough.
It's often impossible to prove a negative assertion, while a positive assertion can often be proved only by demonstration. In this case, the proof will come only when the first nanofactory builds the second nanofactory. But in each field, proponents claim we know the basic scientific principles, and the rest is just R&D.
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Mechanosynthesis
Lab demos of scanning-probe chemistry are arriving rapidly now, but only at a simple single-molecule level.
A diamond-depositing reaction has been Freitas, Merkle, and co-workers.
Deterministic reactions still have to be invented, and large machines and nanomachines have to be developed that can do the required manipulations.
There are quite a few low-temperature stochastic ways of making diamond and buckytubes, but no deterministic ways.
Nanomachines
A few components have been designed and simulated. It looks like kinematic ("robotic") machines will need some design tweaks vs. large-scale machines, but can be approached with mechanical engineering discipline--just different parameters. A few techniques like "frictionless" surfaces (using superlubricity) still have to be worked out.
Once mechanics work, nanoscale power, control, sensing, and computation will be straightforward. It all boils down to mechanics and a little bit of electricity.
Integration
Today's engineering appears sufficient to design and control simple arrays containing huge numbers of similar systems. See for example Chris Phoenix's Nanofactory paper. Even fault tolerance--admittedly necessary--can be implemented with simple redundancy.
Product design
A few nanoscale machines will be reusable to build many nanosystems, and already we're above the level of molecular design. A few systems can be recombined to build many kinds of programmable material. And so on. This is called "levels of abstraction" and lets computers do molar quantities of digital operations without error and within human design ability.
Products of molecular manufacturing will be extremely high performance, due to scaling laws and precision. This means that performance can be traded for simplicity.
Sensing, selection, and failure analysis
A difficulty in developing molecular manufacturing is separating successful trials from failures, and elucidating the failure mechanisms of the failures. Unlike biological evolution, which proceeds by random variations in ensembles of organisms combined with deterministic reproduction/extinction as a selection process to achieve great complexity after billions of years (a set of mechanisms which Richard Dawkins has referred to as a "blind watchmaker"), deliberate design and building of nanoscale mechanisms requires a means other than reproduction/extinction to winnow successes from failures in proceeding from simplicity to complexity. Such means are difficult to provide (and presently non-existent) for anything other than small assemblages of atoms viewable by an AFM or STM.
Extensive modeling before attempting to build is one route toward attacking this problem. But if a complex molecular system becomes an inert lump at some point in its fabrication process, none of the existing destructive analysis techniques (e.g, X-ray diffraction, TEM, STM, gel electrophoresis, mass spectrometry, and the like) offers much power in determining the cause of failure.
It may be argued that this is not a scientific problem, merely a practical one. But a counter to that argument is to assert that the imaginary Maxwell's Demon could not function to select fast molecules from slow if it were deaf, blind, and wearing thick gloves. In the absence of new analytical techniques to pace new design and assembly techniques, the molecular manufacturing effort may stall.

