Killing cancer cells
Given such molecular tools, we could design a small device able to identify and kill cancer cells. The device would have a small computer, several binding sites to determine the concentration of specific molecules, and a supply of some poison which could be selectively released and was able to kill a cell identified as cancerous.
The device would circulate freely throughout the body, and would periodically sample its environment by determining whether the binding sites were or were not occupied. Occupancy statistics would allow determination of concentration. Today's monoclonal antibodies are able to bind to only a single type of protein or other antigen, and have not proven effective against most cancers. The cancer killing device suggested here could incorporate a dozen different binding sites and so could monitor the concentrations of a dozen different types of molecules. The computer could determine if the profile of concentrations fit a pre-programmed "cancerous" profile and would, when a cancerous profile was encountered, release the poison.
Beyond being able to determine the concentrations of different compounds, the cancer killer could also determine local pressure. A pressure sensor little more than 10 nanometers on a side would be sufficient to detect pressure changes of less than 0.1 atmospheres (a little over a pound per square inch. See, for example, the discussion on page 472 et sequitur of Nanosystems[REF06] for the kind of analysis involved. One atmosphere is ~10^5 Pascals, so PV in this case would be (0.1 x 10^5 ) x (10^-8)^3 or 10^4 x 10^ -24 or 10^-20 joules. Multiple samples would be required to achieve reliable operation, as kT is ~4 x 10^-21 joules at body temperature. Linear increases in sensor volume would produce exponential increases in immunity to thermal noise and linear improvements in pressure sensitivity if that were to prove useful. Doubling the linear dimensions of the sensor would produce an eight-fold increase in both volume and pressure sensitivity).
As acoustic signals in the megahertz range are commonly employed in diagnostics (ultrasound imaging of pregnant women, for example), the ability to detect such signals would permit the cancer killer to safely receive broadcast instructions. By using several macroscopic acoustic signal sources, the cancer killer could determine its location within the body much as a radio receiver on earth can use the transmissions from several satellites to determine its position (as in the widely used GPS system). Megahertz transmission frequencies would also permit multiple samples of the pressure to be taken from the pressure sensor, as the CPU would be operating at gigahertz frequencies.
The cancer killer could thus determine that it was located in (say) the big toe. If the objective was to kill a colon cancer, the cancer killer in the big toe would not release its poison. Very precise control over location of the cancer killer's activities could thus be achieved.
The cancer killer could readily be reprogrammed to attack different targets (and could, in fact, be reprogrammed via acoustic signals transmitted while it was in the body). This general architecture could provide a flexible method of destroying unwanted structures (bacterial infestations, etc).
Providing oxygen
Providing oxygen
A second application would be to provide metabolic support in the event of impaired circulation. Poor blood flow, caused by a variety of conditions, can result in serious tissue damage. A major cause of tissue damage is inadequate oxygen. A simple method of improving the levels of available oxygen despite reduced blood flow would be to provide an "artificial red blood cell." We will consider a simple design here: a sphere with an internal diameter of 0.1 microns (100 nanometers) filled with high pressure oxygen at ~1,000 atmospheres (about 10^8 pascals). The oxygen would be allowed to trickle out from the sphere at a constant rate (without feedback). Diamond has a Youngs modulus of about 10^12 pascals. An atomically precise diamondoid structure should be able to tolerate a stress of greater than 5 x 10^10 pascals (5% of the modulus). Thus, a 0.1 micron sphere of oxygen at a pressure of 10^8 pascals could be contained by a hollow diamondoid sphere with an internal diameter of 0.1 microns and a thickness of less than one nanometer.
This thickness, thin as it is, results in an applied stress on the diamond of well under 1% of its modulus -- from a purely structural point of view we should be able to use a very large "bucky ball," i.e., a sphere whose surface is a single layer of graphite. Perhaps the most complex issue involved in the selection of the material is the reaction of the body's immune system. While some suitable surface structure should exist which does not trigger a response by the immune system -- after all, there are many surfaces in the body that are not attacked -- the selection of a specific surface structure will require further research. To give a feeling for the range of possible surface structures, the hydrogenated diamond (111) surface could have a variety of "camouflauge" molecules covalently bound to its surface. A broad range of biological molecules could be anchored to the surface, either directly or via polymer tethers.
The Van der Waals' equation of state is (p+a/v^2) (v-b) = RT, where p is the pressure, v is the volume per mole, R is the universal gas constant, T is the temperature in Kelvins, and a and b are constants specific to the particular gas involved. For oxygen, a = 1.36 atm liter^2/mole^2 and b = 0.03186 liter/mole and R = 0.0820568 liter-atmospheres/mole-kelvin. A mole of oxygen at 1,000 atmospheres and at body temperature (310 Kelvins) occupies 0.048 liters, or about 21 moles/liter. A mole of oxygen at 1 atmosphere and 310 Kelvins occupies 25.4 liters, or about 0.04 moles/liter. This implies a compression of ~530 to 1. A resting human uses ~240 cc/minute[REF32] of oxygen, so a liter of oxygen compressed to 1,000 atmospheres should be sufficient to maintain metabolism for about 36 hours (a day and a half). It might be desirable to replace less than a liter of blood with our microspheres of compressed oxygen, but it should still be quite feasible to provide oxygen to tissue even when circulation is severely compromised for periods of at least many hours from a single infusion.
Controlled release of oxygen from the diamondoid sphere could be done using the selective transport method proposed by Drexler[REF06] and illustrated in figure 3. Figure 3 shows transport in the "wrong" direction (for this application), but simply reversing the direction of rotor motion would result in transport from inside the reservoir to the external fluid. By driving a rotor at the right speed, oxygen could be released from the internal reservoir into the external environment at the desired rate.
Figure 3.
More sophisticated systems would release oxygen only when the measured external partial pressure of oxygen fell below a threshold level, and so could be used as an emergency reserve that would come into play only when normal circulation was (for some reason) interupted.
Full replacement of red blood cells would involve the design of devices able to absorb and compress oxygen when the partial pressure was above a high threshold (as in the lungs) while releasing it when the partial pressure was below a lower threshold (as in tissues using oxygen). In this case, selective transport of oxygen into an internal reservoir (by, for example, the method shown in Figure 3) would be required. If a single stage did not provide a sufficiently selective transport system, a multi-staged or cascaded system could be used. Compression of oxygen would presumably require a power system, perhaps taking energy from the combustion of glucose and oxygen (thus permitting free operation in tissue). Release of the compressed oxygen should allow recovery of a significant fraction of the energy used to compress it, so the total power consumed by such a device need not be great.
If the device were to simultaneously absorb carbon dioxide when it was present at high concentrations (in the tissue) and release it when it was at low concentrations (in the lungs), then it would also provide a method of removing one of the major products of metabolic activity. Calculations similar to those given above imply a human's oxygen intake and carbon dioxide output could both be handled for a period of about a day by about a liter of small spheres.
As oxygen is being absorbed by our artificial red blood cells in the lungs at the same time that carbon dioxide is being released, and oxygen is being released in the tissues when carbon dioxide is being absorbed, the energy needed to compress one gas can be provided by decompressing the other. The power system need only make up for losses caused by inefficiencies in this process. These losses could presumably be made small, thus allowing our artificial red blood cells to operate with little energy consumption.
By comparison, a liter of blood normally contains ~0.2 liters of oxygen[REF32, page 1722], while one liter of our spheres contained ~530 liters of oxygen (where "liter of oxygen" means, as is common in the literature on human oxygen consumption, one liter of the gas under standard conditions of temperature and pressure). Thus, our spheres are over 2,000 times more efficient per unit volume than blood; taking into account that blood is only about half occupied by red blood cells, our spheres are over 1,000 times more efficient than red blood cells.
Failure of a 0.1 micron sphere would result in creation of a bubble of oxygen less than 1 micron in diameter. Occasional failures could be tolerated. Given the extremely low defect rates projected for nanotechnology, such failures should be very infrequent.
Artificial mitochondria
While providing oxygen to healthy tissue should maintain metabolism, tissues already suffering from ischemic injury (tissue injury caused by loss of blood flow) might no longer be able to properly metabolize oxygen. In particular, the mitochondria will, at some point, fail. Increased oxygen levels in the presence of nonfunctional or partially functional mitochondria will be ineffective in restoring the tissue. However, more direct metabolic support could be provided. The direct release of ATP, coupled with selective release or absorption of critical metabolites (using the kind of selective transport system mentioned earlier), should be effective in restoring cellular function even when mitochondrial function had been compromised. The devices restoring metabolite levels, injected into the body, should be able to operate autonomously for many hours (depending on power requirements, the storage capacity of the device and the release and uptake rates required to maintain metabolite levels).
Further possibilities
It is clear that this approach should be able to reverse substantially greater damage than can be dealt with today. A primary reason for this is that autonomous molecular machines using externally provided power would be able to continue operating even when the tissue itself was no longer functional. We would finally have an ability to heal injured cells, instead of simply helping injured cells to heal themselves.
Advances in medical technology necessarily depend on our understanding of living systems. With the kind of devices discussed earlier, we should be able to explore and analyze living systems in greater detail than ever before considered possible.
Autonomous molecular machines, operating in the human body, could monitor levels of different compounds and store that information in internal memory. They could determine both their location and the time. Thus, information could be gathered about changing conditions inside the body, and that information could be tied to both the location and the time of collection. Physical samples of small volumes (nano tissue samples) could likewise be taken.
These molecular machines could then be filtered out of the blood supply and the stored information (and samples) could be analyzed. This would provide a picture of activities within healthy or injured tissue. This new knowledge would give us new insights and new approaches to curing the sick and healing the injured.
