Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
3.4.2 Sorting Rotors
Drexler's molecular sorting rotor10 is a related class of nanomechanical device capable of selectively binding molecules from solution and then transporting these bound molecules against concentration gradients (Fig. 3.7). The archetypal sorting rotor is a disk with 12 binding site "pockets" along the rim exposed alternately to the external solution and interior chamber by axial rotation of the disk. (Other designs may have more, or fewer, pockets.) Each pocket selectively binds a specific molecule when exposed to the solution. Once the binding site (Section 3.5) rotates to expose it to the interior chamber, the bound molecules are forcibly ejected by rods thrust outward by the cam surface (or using some other means by which receptor affinity can be adjusted during the inbound transport process). In the case of protein molecules, the debinding geometry must be carefully designed to avoid denaturation during ejection. Also, the rotor in Figure 3.7 implicitly assumes that target molecules remain in the liquid or gaseous state after importation. M. Krummenacker observes that most bloodborne molecular species will precipitate as solids unless they are well-solvated; thus nanomedical sorting systems may require internal solvent or in some cases should be made completely eutactic (Section 3.4.3). The discovery of positionally disordered water molecules resident inside protein hydrophobic cavities1047 suggests that good rotor designs may also need to include solvent drainage channels.
Molecular sorting rotors can be designed from about 105 atoms (including housing and pro rata share of the drive system), measuring roughly 7 nm x 14 nm x 14 nm in size with a mass of 2 x 10-21 kg. Rotors turn at ~86,000 rev/sec with a conservative rim speed of 2.7 mm/sec and an almost negligible drag power of ~10-16 watts against the fluid, sorting small molecules at a rate of 106 molecules/sec with laminar flow. From Eqn. 3.18, the energy cost of small-molecule sortation at 310 K ranges from ~10 zJ/molecule at low pressures (c2/c1 = 10) up to ~40 zJ/molecule when pumping against the highest head pressures (c2/c1 = 104, ~30,000 atm for natural bloodstream concentrations of salt with osmotic pp ~ 3 atm), consuming 0.01-0.04 pW per device in continuous operation. Rotors are fully reversible, so they can be used to load or unload target molecules depending on the direction of rotor rotation. Cylindrical rotors with many receptor rows are somewhat more energy-efficient, and rotor lifetimes10 should be >106 sec (Chapter 13).
Typical molecular concentrations in the blood for target molecules of nanomedical interest are ~10-11 10-3 molecules/nm3, which should be sufficient to ensure ~99% occupancy of rotor binding sites (Section 3.5.2). Rotors targeting serum hormones and other low-concentration species at the parts-per-billion level must slow to <1 rev/sec to ensure complete receptor occupancy and to avoid exceeding diffusion limits.
Sorting of ionically charged species can use binding sites that display opposite charge, effectively increasing the affinity of the binding site for the charged species. Many ionic species dissolved in water are actually more complex than their symbolic representation would suggest. As an example, a naked proton (H+) in water is always highly hydrated, usually as H5O2+ or H7O3+,996 or even as H9O4+ in strong acid solutions.2337 Small ions from Li+ to I are also found in solvent cages, bound with energies >330 zJ relative to vacuum;2338 for instance, Li+ and I- are coordinated to 46 water molecules.1149,3235 As a result, the design of an appropriate binding site or filtration process for such ions can likewise become more complex. The existence of biological channels that show remarkable selectivity for specific ions (e.g., Na+ channels that largely exclude K+ ions, and vice versa; Section 3.4.1) provides one design approach for dealing with such species.
Drexler10 has also proposed cascades of sorting rotors (Fig. 3.8) to achieve high fidelity purification and a contaminant fraction of <10-15. However, since only ~1010 small molecules can be stored in 1 micron3 volume (typical for nanomedical devices), 100% process purity requires a contaminant fraction of only <10-10 which can be ensured in micron-scale nanosystems using at most 5 stages, starting from a dilute input substrate containing only 1 part per billion of the target molecule with each stage providing a concentration factor of ~104. For statistically pure extractions of more common molecules in blood and cytoplasm, a 3- or 4-stage cascade will usually suffice. Note that the optimal receptor structure may differ at different stages in a cascade,10 and that each 12-arm outbound rotor can contain binding sites for 12 different impurity molecules. The first-stage receptor will likely pass only a relatively small number of different contaminant species, so the number of outbound rotors in the entire system can probably be reduced to a small fraction of the number of inbound rotors.
Last updated on 7 February 2003