22. Biological Molecules in Therapeutic Nanodevices

In this chapter, we discuss the incorporation of molecules into nanodevices as functional device components. Our primary focus is on biological molecules, although we also discuss the use of organic molecules as functional components of supramolecular nanodevices. Our primary device interest is in devices used in human therapy and diagnosis, though when it is informative, we discuss other nontherapeutic nanodevices containing biomolecular components. We discuss design challenges associated with devices built from prefabricated components (biological macromolecules) but that are not as frequently associated with fully synthetic nanodevices. Some design challenges (abstraction of device object properties, inputs, and outputs) can be addressed using existing systems engineering approaches and tools (including unified modeling language), whereas others (selection of optimal biological macromolecules from the billions available) have not been fully addressed. We discuss various assembly strategies applicable to biological macromolecules and organic molecules (self-assembly, chemoselective conjugation) and their advantages and disadvantages. We provide an example of a functional mesoscale device, a planar field-effect transistor (FET) protein sensor, that depends on nanoscale components for its function. We also use the sensor platform to illustrate how protein and other molecular engineering approaches can address nanoscale technological problems, and argue that protein engineering is a legitimate nanotechnology in this application. In developing the functional FET sensor, both direct adsorption of protein analyte receptors as well as linkage of receptors to the sensing surface through a polymer layer were tested. However, in the realized FET sensor, interfaces consist of a polymer layer linked to the semiconductor surface and to an analyte receptor (a protein). Nanotribology and other surface-science investigations of the interfaces revealed phenomena not previously documented for nanoscale protein interfaces (lubrication by directly adsorbed proteins, increases in friction force associated with polymer-mediated increases in sample compliance). Furthermore, the studies revealed wear of polymer and receptor proteins from semiconductor surfaces by an atomic force microscopy (AFM) tip which was not a concerted process, but rather depth of wear increased with increasing load on the cantilever. These studies also revealed that the polymer–protein interfaces were disturbed by nanonewton forces, suggesting that interfaces of immunoFET protein sensors translated to in vivo use must likely be protected from, or hardened to endure, abrasion from tissue. The results demonstrate that nanoscience (in this case, nanotribology) is needed to design and characterize functional planar immunoFET sensors, even though the sensors themselves are mesoscale devices. The results further suggest that modifications made to the sensor interfaces to address these nanoscale challenges may be best accomplished by protein and interfacial engineering approaches.