Nanomedicine, Volume IIA: Biocompatibility
© 2003 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003
18.104.22.168 Biofouling of Medical Nanorobots
Another biocompatibility issue in nanorobotic medicine is biofouling [4749-4755] – the possible incapacitation of nanorobotic systems which may become jammed with biological macromolecules, structures, microorganisms, or debris. The biocompatibility of medical nanorobots made of diamond has already been reviewed (Section 15.3.1), but such nanorobots likely will not present smooth unbroken surfaces to the in vivo environment. Rather, nanorobot surfaces will frequently be interrupted by various transtegumental structures such as sorting rotor binding sites (Section 3.4.2), chemical sensors (Section 4.2), pressure sensors (Section 4.5), energy transducers (Section 6.3), communications transducers (Section 7.2), manipulatory appendages (Section 9.3), and so forth. The biocompatibility of each of these structures (or their fragments; Section 15.4.4) must be separately assessed, and assessed in various plausible combinations. A comprehensive evaluation is beyond the scope of this introductory text.
The biocompatibility of exposed chemical binding sites found on binding pads, sensors, or sorting rotors used for molecular transport, and ligand presentation surface moieties (Section 22.214.171.124) may be the easiest to analyze. Small-molecule receptors probably will avoid antibody recognition due to steric constraints. Macrophages and other phagocytic cells should not be able to recognize rapidly spinning synthetic sorting rotor binding sites, which are deeply embedded in an otherwise passive diamondoid structure. Nor should these cells be able to recognize display ligands (Section 5.3.6), which are presented and then retracted a short time later. Artificial monoclonal antibodies are easily raised against natural biological receptor sites , but natural antibodies to such receptors normally have been removed by clonal deletion and thus should not be available to participate in an interaction with medical nanorobot receptors whose structure is homologous to the natural receptors. Natural antagonists to receptors for highly regulated cytokines [2156-2160] and similar biomolecules may exist in the body, and might therefore also be available to interact with artificial nanorobot binding sites. However, such interactions may be minimized (1) by careful design of sorting rotor competitive binding site specificities, (2) by employing recessed active structures and self-cleaning grilles, and (3) by executing preprogrammed prophylactic nanorobot behaviors such as periodic counterrotational backflushing of all binding sites. Designers also must avoid creating binding sites which might inadvertently trigger cytotoxic reactions. For instance, silicic acid and silica particles are hemolytic, inducing permeability changes in biological membrane systems . The biocompatibility of enzymes immobilized on surfaces in experimental therapies has also been studied .
Possible biofouling or clogging of nanosieve pores (Section 3.3.1), nanoscale pipes (Section 9.2.5), spinning molecular sorting rotors (Section 126.96.36.199), protruding telescoping manipulators (Section 188.8.131.52), nonadhesive (Section 184.108.40.206) and adhesioregulatory (Section 220.127.116.11) nanorobot surfaces, and implant surfaces with bacterial overgrowths or biofilms (Section 18.104.22.168) have already been discussed, at least briefly, elsewhere in this book series. Biofouling by microorganisms is of particular interest because early nanodevices may be involved in bulk production processes for pharmaceutical agents such as antibiotics and drugs, for food products such as cheese, and for many other industrial materials, long before the introduction of suspensions of sophisticated nanorobots into the human body is permitted. It has long been known  that bacteria adhere to Teflon in continuous culture of the sort commonly employed in biotechnology production methods , and may form biofilms on Teflon [1225-1227, 1358-1361] (Section 22.214.171.124(12)). Bacteria may also grow well on graphite surfaces (Section 126.96.36.199), though rigorous studies of biofilms on diamond have not been published in the literature.
Finally, nanoscale pores, pipes, rotors, manipulators, and active surfaces are subject to possible damage by free radicals or other highly reactive moieties that may be present in the natural biological environment in which nanorobots must operate for extended periods of time. While graphene sheets are largely impervious to carbon radicals (Section 188.8.131.52), intact diamond surfaces are susceptible to chemical attack by atomic oxygen (Section 184.108.40.206.6 (I)) and non-intact diamond (Section 220.127.116.11.6 (I)) and sapphire (Section 18.104.22.168.6 (I)) surfaces are even more susceptible. J. Soreff (Section 22.214.171.124.6 (IV)) has suggested that microbes could be designed that are capable of applying excited oxidants such as singlet oxygen to breach a diamond surface. No in vivo studies have yet been reported, though H-passivated diamond cannot resist free radical attack by photodissociated products of fluoroalkyl iodides  and at least one other instance of diamond/free-radical activity is known . As a useful benchmark, Drexler  notes that “proteins in living systems provide a model for molecular machines in a relatively complex, chemically aggressive environment. Metabolic enzymes can have lifetimes of several days , despite the relative fragility of protein structures.” The lifetime of a single unprotected diamondoid sorting rotor of greater chemical stability may be even longer, perhaps on the order of ~106 sec.
Several methods may be used to extend this operational lifetime. For example, medical nanorobot designs commonly include tenfold redundancy in sorting rotors [2762, 3573], manipulator arms , and other mechanisms  exposed to natural biological fluids. Since rotors can be safely banked until needed, the simple expedient of sequentially engaging spares when active units are damaged may extend mission lifetime by up to a factor of ten, given tenfold redundancy of the affected mechanisms; thousandfold or higher redundancies may be practical for the most critical fluid-exposed medical nanorobot components. Another alternative, suggested by Drexler  in a different context, involves the use of sacrificial getters positioned anterior in the fluid flow to susceptible components: “Damage resulting from trace quantities of highly reactive contaminants can be minimized by flowing feedstock solutions past surfaces bearing bound moieties resembling those used on critical rotor surfaces, but selected for higher reactivity. Sacrificial moieties of this sort can combine with and neutralize many reactive species, including free radicals.” Such getters could be positioned along the walls of access channels leading to enclosed sorting rotors, with getter moieties mounted on detachable tool tips in the manner of presentation semaphores (Section 5.3.6) and either recycled, refurbished or replaced from internal inventory as needed. A related biocompatibility concern is whether diamondoid surfaces, once attacked or covalently bonded by active moieties, become more visible to the immune, complement, inflammatory, or thrombogenic systems of the human body. These subjects deserve further research.
Last updated on 30 April 2004