Microbivores - Extended Applications

Extended Applications

Microbicores as a general class of medical nanorobots, have much broader applicability which goes beyond the idea of phagocytosis of isolated bloodborne bacterial pathogens. Microbivores could be useful in the treatment of infections of the meninges and the cerebrospinal fluid (CSF) by quickening the kill rate as opposed to typical antibotic treatments.

Microbivores could also be used used in systemic inflammatory cytokine management. With minor additions, microbivores could be used to combat toxemia, the distribution throughout the body of poisonous products of bacteria growing in a focal or local site, and other biochemical sequelae of sepsis. Often times even when killing a certain bacteria byproducts are produced that can significantly harm the body. Since in the microbivores all the bacteria components are internalized and fully digested into harmless nonantigenic molecules prior to discharge from the device, the nanorobots represent a complete antimicrobial therapy without increasing the risk of sepsis or septic shock.

In addition microbivores, slightly altered, could also be used to digest bacterial biofilms. Biofilms may vary widely in thickness, which is limited more by nutrient transport than by surface roughness. Microbivores can digest biomaterial at a rate of ~4 micron3/min, hence an array of closely packed microbivores (~6.8 micron2/device) attached to a biofilm can consume the biofilm at a rate of ~10 nm/sec, requiring ~105 sec (~3 hr) to consume an entire 100-micron thick biofilm. Again, some means must be found to ensure a watertight seal between partially fragmented organisms and the microbivore ingestion port.

Microbivores could also aid in treatment of bacterial infections of other fluids and tissues. Bacteria present in sputum or in the mucous layers of the throat may be pursued by somewhat larger ambulatory microbivores having an additional array of longer grapples that could serve as locomotive mechanisms (legs), thus permitting the nanorobots to engage in microbial search-and-destroy missions along the luminal surfaces of the human trachea, bronchi, and bronchioles. With additional modifications, other variants of microbivores could patrol tissues, organs, and nonsanguinous fluid spaces such as pleural , synovial , or urinary fluids, pursuing bacteria as they disseminate beyond the bloodstream. Vasculomobile microbivores could follow cytokine gradients and collect at sites of infection, thus increasing their microbicidal efficiency.

Microbivores could also be used to rid the blood of viral pathogens, which are typically present during viremia at concentrations similar to those found in bacteremia. Viruses tend to be much smaller than most bacteria, so processing time per virion may be considerably reduced, perhaps 5-10 seconds or less. Apparently the human body is already fairly efficient at removing virus particles from the bloodstream. The difficulty for the natural defensive systems is that replacement viruses are rapidly replicated and discharged into the blood by infected cells, thus perpetuating the infection. These high production rates are nevertheless easily controlled by a terabot population of microbivores which has a collective digestive capacity of >1015 virions/day. One additional complication, well within the competence of the the current microbivore design, is that some viruses like HIV are mutating constantly, so that one patient may have as many as 8-10 different strains concurrently, all of which must be successfully recognized and eliminated.

Fungemias involving particle loads of 1-1000 CFU/ml are rapidly cleared by microbivores. Fungal particles may be up to ~400 micron3 in volume, requiring ~100 min for complete digestion using a microbivorous protocol that employs careful piecewise digestion involving ~800 "bites". Blood parasites of comparable size may be present at concentrations similar to those found in bacteremia but may be controlled with terabot doses of microbivores. Microbivorous also could be helpful in aiding in biofilm digestion, aiding in bacterial Infections in other fluids and tissues, aiding in viral, fungal, and parasitic infections and other useful treatments.

Other Applications

Microbivores could be designed to trap and retain (without digesting) samples of unknown microbes found floating in the bloodstream, when those microbes fall within a certain physician-specified size range and are confirmed not to be platelets or chylomicrons. These samples could then be returned to the attending physician for further investigation, following nanapheresis. Ranging still further afield, microbivore-derived devices could be employed in veterinary and military applications; to disinfect surfaces, objects, and volumes (e.g., 102-105 CFU/ml bacteria found in the sink fluid of washbasin drains in a pediatric ward or to sterilize organic samples or edible foodstuffs; to clean up biohazards, biopolluted drinking water, toxic biochemicals, or other environmental organic materials spills, as in bioremediation; and in many other useful applications.

The Future?

This website presents a theoretical nanorobot scaling study for artificial mechanical phagocytes of microscopic size, called "microbivores," whose primary function is to destroy microbiological pathogens found in the human bloodstream using a digest and discharge protocol.

The microbivore is an oblate spheroidal nanomedical device measuring 3.4 microns in diameter along its major axis and 2.00 microns in diameter along its minor axis, consisting of 610 billion precisely arranged structural atoms in a gross geometric volume of 12.1 micron3. During each cycle of operation, the target bacterium is bound to the surface of the microbivore via species-specific reversible binding sites. Telescoping robotic grapples emerge from silos in the device surface, establish secure anchorage to the microbe's plasma membrane, then transport the pathogen to the ingestion port at the front of the device where the cell is internalized into a morcellation chamber. After sufficient mechanical mincing, the morcellated remains are pistoned into a digestion chamber where a preprogrammed sequence of engineered enzymes are successively injected and extracted, reducing the morcellate primarily to monoresidue amino acids, mononucleotides, glycerol, free fatty acids and simple sugars, which are then harmlessly discharged into the environment, completing the cycle.

The device may consume up to 200 pW of continuous power while completely digesting trapped microbes at a maximum throughput of 2 micron3 of organic material per 30-second cycle. Microbivores are up to ~1000 times faster-acting than either natural or antibiotic-assisted biological phagocytic defenses, and are ~80 times more efficient as phagocytic agents than macrophages, in terms of volume/sec digested per unit volume of phagocytic agent. Besides intravenous bacterial scavenging, microbivores or related devices may also be used to help clear respiratory, urinary, or cerebrospinal bacterial infections; eliminate bacterial toxemias and biofilms; eradicate viral, fungal, and parasitic infections; disinfect surfaces, foodstuffs, or organic samples; and help clean up biohazards and toxic chemicals.

Sources

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

Institute for Molecular Manufacturing. Report No. 25. Nanomedicine: Microbivores, Artificial Mechanical Phagocytes by Robert A. Freitas Jr. Published April 1, 2001.

http://www.nlm.nih.gov/medlineplus/ency/article/000666.htm

Pictures and Tables

1 http://www.foresight.org/Nanomedicine/Gallery/Captions/Image197.html

2 http://www.agen.ufl.edu/~chyn/age2062/lect/lect_06/lect_06.htm

3 http://www.foresight.org/Nanomedicine/Gallery/Captions/Image197.html

4 http://www.medizin.fu-berlin.de/trauma/ertel/site.php?object=6&resid=58&restype=2&print=1

5 http://www.theepochtimes.com/news/5-5-31/29150.html

6 http://www.sci.utah.edu/~erikj/Port/futsci/futsci.html

7 http://www.foresight.org/Nanomedicine/Gallery/Images/microbivore_lge.jpg

8 http://www.nanomedicine.com/NMI/Figures/4.2.jpg

9 http://www.nanomedicine.com/NMI/Figures/5.14.jpg

10 K. Eric Drexler, Nanosystems: Molecular Machinery, Manufacturing, and Computation, John Wiley & Sons, NY, 1992.

11 http://www.rfreitas.com/Nano/Microbivores.htm

12 http://www.nanotech-now.com/Art_Gallery/tim-fonseca.htm