(part of Steps Toward Molecular Manufacturing)

- positional control:

In order to stack differently functionalized MBBs into a lattice in a specified and complex pattern, it is necessary to introduce positional control. As a crystalline object under construction will provide many potential reaction sites, one has to be able to select the specific site where the next MBB is to be attached. Without such a controlled assembly technique, the type of molecular aggregates one will be able to make will be restricted to regular crystals, not containing the complicated patterns that are needed for certain lucrative applications. It seems as if regular symmetry were the antagonist to complexity. As a matter of fact, all traditional macroscopic machinery is chiral, and hence completely asymmetric. Indeed, given the macroscopically observable wealth of complicated biological structures, it is not surprising to find that the underlying enzymatic machinery of biochemistry must be chiral too, in order to generate this kind of complexity.

Because of the fundamental character of asymmetry, it is necessary to be able to also stack artificial MBBs in arbitrary ways that lead to chiral and asymmetric structures. Starting from MBBs which are chiral themselves, it is clear that this can be achieved, but it can also be accomplished by using achiral MBBs and introducing the asymmetry through the construction process by using a device that provides positional control (which in itself will always be a chiral entity!).

Macroscopic devices that provide positional control with atomic precision have been constructed now for many years, but they have been mainly used in an analytical mode to obtain high resolution images of all kinds of surfaces. An approach to using an atomic force microscope (AFM) in a constructional mode has been proposed in chapt.15.4 of [Dre92]. The strategy is to develop a rigid attachment procedure for antibody Fv-fragments, the smallest antibody fragments that still contain the full binding specificity, and on the AFM, both the flat surface which is traditionally the imaged part, as well as beads mounted on the cantilever tip are to be coated with these antibodies. This leads to a situation where there are antibodies on both sides of the AFM mechanism and can act as specific receptors. For this device, antibodies could be generated which bind small organic molecules having reactive functional groups, namely the MBBs, which will enable the mutual positioning of the reactive groups above each other to atomic precision, and to thus forge a chemical reaction at the desired location, but nowhere else. The local effective concentration that can be achieved upon positioning the tip could be made to exceed 100M, and a background concentration of MBBs in the surrounding solution in the µM range is compatible with the affinities of antibodies. The difference in reaction rates between the selected reaction site and everywhere else should thus be of the order of 100,000,000. Such a large signal-to-noise ratio should allow the execution of at least 10'000 consecutive reaction steps on one substrate, which is unprecedented in organic chemistry.

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last updated Oct. 5 1996
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