Page 39 - Nanotechnology an introduction

then direct the repair work, much in the way that certain operations are already carried out today by remotely controlling tools fitted to the end of an
endoscope, for example. In this case, the requisite nano/bio interface will be the same as the man–machine interface made familiar through digital
information processing technology: the man–machine interface has been a preoccupation of computer scientists ever since the inception of
information technology (IT). At present, the issue scarcely arises for nanotechnology, since we do not yet have sophisticated nanosystems that
need to be interfaced. The closest current realizations of assemblers operating with atomic precision are tip-based scanning probe devices that
are digitally controlled; their nano/bio interface is indeed a standard IT man–machine interface. This kind of control will, however, be far too
cumbersome for assemblers that are themselves nanosized—the lags in regulation would tend to generate chaos—hence the assemblers will need
to operate with a great deal of autonomy. Although the current generation of screen-based graphical user interfaces (GUI) might be slightly more
convenient than punched tape or cards, the laborious letter by letter entry of instructions or data via a keyboard remains slow, frustrating and error-
prone. While hardware continues to advance exponentially (Moore's law), software and the man–machine interface continue to lag behind and limit
human exploitation of IT.

Also encompassed within this meaning of the nano/bio interface is how a nanomachine can produce at the human scale. For example, a single
nanostructured microsystem may synthesize only attograms of a valuable medicinal drug, too little even for a single dose administered to a patient.
The solution envisaged is scaleout, i.e., massive parallelization—the chemical reactor equivalent of parallel computing. This has already been
realized, albeit on a modest scale involving less than a dozen microreactors.
4.1. The “Physical” Nano/Bio Interface

From the biological viewpoint, the nano/bio interface can be considered at three scales at least (examples given in parentheses):
1. the organismal scale (e.g., wearing clothing made from a nanomaterial)
2. the cellular scale (e.g., cell adhesion to a nanomaterial)
3. the molecular scale (e.g., protein adsorption to a nanomaterial).
There is an additional interface above the organismal scale, namely between society and nanotechnology, which comprises several unique
features and will be dealt with separately (Chapter 12). The nano/bio interface can be considered a special case of the living–nonliving (or bio–
nonbio) interface, in which the nonliving side has nanoscale features. If it is a nanomaterial (a nanostructured material or a nano-object), then many
of the issues have been dealt with in a general way under the rubric of biocompatibility. If it is a nanodevice, then the issues are likely to belong to
metrology (Chapter 5) or to bionanotechnology (Chapter 11). If it is a nanosystem, then effectively it will be interacting with a system on the living
side, and we are again in the realm of the interface between society and nanotechnology (Chapter 12). The focus in the following sections is how
the presence of nanoscale features introduces unique behavior not present otherwise.

4.1.1. Organisms

It is a moot point whether nanostructure is perceptible by organisms. Certainly it is not directly visible, given that the organs of sight use visible light.
We have rather to ask whether we could otherwise become aware of (e.g., feel) a difference between a textile woven from a nanostructured fiber
and one that was not, for example. Indirectly there might be no difficulty; a cravat whose fibers are nanostructured to make them water-repellent
would be immediately distinguishable using the naked eye from an ordinary one. Natural fibers of course have structure at the nanoscale, but they
are not nanostructured in the sense of being deliberately engineered at that scale. Similar considerations apply to foodstuffs: two aliments of the
same overall composition may well feel different when first placed in the mouth if they have different structure at the nanoscale, but if this structure
has not been deliberately engineered then we are not talking about nanotechnology according to the definitions (Section 1.1). Experiments to
determine whether deliberately differently engineered structures are differently perceived do not yet appear to have been carried out in a sufficiently
systematic fashion to be useful; indeed this aspect of the nano/bio interface is, as yet, practically unexplored.
The study of the deleterious biological consequences of nano-objects, especially nanoparticles, penetrating into the body constitutes the field of
nanotoxicology (see Section 4.3). Particles may gain access to the body by inhalation, ingestion, through the skin, or following the introduction of
material in some medical procedure such as implantation. If they are introduced into the blood they are likely to be taken up by the macrophage
system (see also Section 4.1.3). Toxic, or at any rate inflammatory, effects may arise indirectly through the adsorption of blood proteins on the
surface of a particle and their subsequent denaturation (see Section 4.1.4). In other words, the effects on the overall organism depend on
processes involving suborganismal scales down to that of molecules.

4.1.2. Tissues

The tissue–substratum interface has been intensively investigated for many decades, starting long before the era of nanotechnology, in the search
to develop more biocompatible orthopedic and dental implant materials. It has long been realized that a rough prosthesis will integrate better into
existing bone than a smooth one. Contrariwise, an ultrasmooth stent is known to be less prone to adsorb proteins from the bloodstream than a
rough one. This knowledge has not yet, however, been systematically refined by correlating nanoscale morphological features with the rate and
quality of assimilation. Although surfaces have been treated so as to incorporate certain molecules into them, this has been done in a (bio)chemical
fashion rather than in the spirit of atomically precise engineering, and there has been no comprehensive systematic study of nanoscale features
evoking a response not seen otherwise, and disappearing if the features are enlarged up to the microscale.
The tissular nano/bio interface is of acute interest to the designers of nanoparticles for drug delivery. The main general challenge is achieving long
circulation times of the nanoparticles in the bloodstream, which is in turn achieved by evading opsonization. This is thus a problem of protein
adsorption, dealt with in detail in Section 4.1.4. There is also the question of how the nanoparticles are eliminated after they have done their work.
Since solubility increases with increasing curvature according to the Gibbs–Thomson law (equation 2.4), the smaller the particle radius, the faster it
will dissolve. Designers of surgical instruments are often concerned with tribology aspects. Although naively it might seem that a perfectly smooth
surface would have the lowest coefficient of friction, asperity serves to diminish contact area and, hence, may even be advantageous. Nano-
engineered asperity has, as yet, been incompletely explored as a route to controlling the friction experienced by objects in contact with tissue. An
interesting research direction seeks to harness biological lubricants, notably the ubiquitous glycoprotein mucin, in order to control friction [170]. A
further aspect of the tissue–nanomaterial interface is biomineralization. The tough, hard shells of marine organisms such as the abalone have a