Jeremy J. Ramsden

What is Nanotechnology

This introductory chapter defines nanotechnology and introduces the rudiments of a concept system (ontology) for it. The history of nanotechnology is outlined, and the way in which the discoveries of molecular biology have made biology into a paradigm for nanotechnology is explained. The convergence of nanotechnology, biotechnology, information technology and the cognitive sciences is discussed. Finally, the principal motivations for nanotechnology are outlined.

The Transmission of Information

The content of this chapter comprises the basics of information transmission, which include some or all of: the information source, encoding the information, transmitting it through a channel, the addition of noise and, finally, receiving and decoding the information. Biological coding is introduced through the examples of DNA, RNA and proteins. Further topics dealt with include the compression of information (and its use to measure distance), ergodicity, and error correction. Noise is given particular attention and the concept of equivocation to quantify the amount of information lost in transmission due to noise is introduced.

Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243u2005μm−2 (corresponding to a 3D dissociation constant of ~30u2005μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels.

Immobilization of proteins to lipid bilayers

Phospholipid bilayers deposited on sensor surfaces are excellent substrates for immobilizing proteins via a molecular anchor. An integrated optics sensing device was used to accurately measure the binding kinetics of proteins thus anchored. By comparing the results with measurements using proteins from which the anchor had been enzymatically removed, it was shown that the anchor accounts for essentially all the irreversible binding. The insertion of the anchor into the lipid bilayer is a spontaneous process. This method of immobilization should be widely applicable to many soluble protein molecules, to which an anchor can be attached by routine methods of molecular engineering.

BIOMIMETIC PROTEIN IMMOBILIZATION USING LIPID BILAYERS

Abstract Biosensors typically consist of a transducer (sensing pad) coated with biomolecules capable of acting as receptors for an analyte in solution to which the device is then exposed. The overall response of the biosensor is determined not only by the characteristics of the sensing pad, but also by the characteristics of the biomolecular receptor (capture) layer. This paper describes how lipid bilayers can be used advantageously to create stable protein monolayers on a transducer surface.

Sample handling in surface sensitive chemical and biological sensing: a practical review of basic fluidics and analyte transport.

This paper gives an overview of the advantages and associated caveats of the most common sample handling methods in surface-sensitive chemical and biological sensing. We summarize the basic theoretical and practical considerations one faces when designing and assembling the fluidic part of the sensor devices. The influence of analyte size, the use of closed and flow-through cuvettes, the importance of flow rate, tubing length and diameter, bubble traps, pressure-driven pumping, cuvette dead volumes, and sample injection systems are all discussed. Typical application areas of particular arrangements are also highlighted, such as the monitoring of cellular adhesion, biomolecule adsorption-desorption and ligand-receptor affinity binding. Our work is a practical review in the sense that for every sample handling arrangement considered we present our own experimental data and critically review our experience with the given arrangement. In the experimental part we focus on sample handling in optical waveguide lightmode spectroscopy (OWLS) measurements, but the present study is equally applicable for other biosensing technologies in which an analyte in solution is captured at a surface and its presence is monitored. Explicit attention is given to features that are expected to play an increasingly decisive role in determining the reliability of (bio)chemical sensing measurements, such as analyte transport to the sensor surface; the distorting influence of dead volumes in the fluidic system; and the appropriate sample handling of cell suspensions (e.g. their quasi-simultaneous deposition). At the appropriate places, biological aspects closely related to fluidics (e.g. cellular mechanotransduction, competitive adsorption, blood flow in veins) are also discussed, particularly with regard to their models used in biosensing.

Porosity of pyrolysed sol–gel waveguides

The pyrolysis of a sol–gel film dip-coated on a substrate is a convenient and inexpensive way of preparing optical waveguides with a wide range of refractive indices. Such waveguides are, however, microporous. For many uses, in particular sensing applications such as the chemical analysis of solutions, the porosity is one of the key parameters determining the response of the waveguide to its environment. In this paper, the porosity of a planar waveguide is accurately determined by measuring the mode indices for two modes with the pores filled alternately with liquid H2O and D2O.

Enhanced protein adsorption and cellular adhesion using transparent titanate nanotube thin films made by a simple and inexpensive room temperature process: Application to optical biochips

A new type of titanate nanotube (TNT) coating is investigated for exploitation in biosensor applications. The TNT layers were prepared from stable but additive-free sols without applying any binding compounds. The simple, fast spin-coating process was carried out at room temperature, and resulted in well-formed films around 10nm thick. The films are highly transparent as expected from their nanostructure and may, therefore, be useful as coatings for surface-sensitive optical biosensors to enhance the specific surface area. In addition, these novel coatings could be applied to medical implant surfaces to control cellular adhesion. Their morphology and structure was characterized by spectroscopic ellipsometry (SE) and atomic force microscopy (AFM), and their chemical state by X-ray photoelectron spectroscopy (XPS). For quantitative surface adhesion studies, the films were prepared on optical waveguides. The coated waveguides were shown to still guide light; thus, their sensing capability remains. Protein adsorption and cell adhesion studies on the titanate nanotube films and on smooth control surfaces revealed that the nanostructured titanate enhanced the adsorption of albumin; furthermore, the coatings considerably enhanced the adhesion of living mammalian cells (human embryonic kidney and preosteoblast).

The music of the nanospheres

The generally promulgated vision of nanotechnology in the future is all-encompassing. Both its proponents and opponents are united in declaring that significant developments will take place. Assessing what has already been done, one can assert the following: nanodevices are ubiquitous in electronic equipment, especially microprocessor circuits and peripheral equipment, such as random access (RAM) and read only memory (ROM) chips, and other data storage media and their associated writers and readers. That alone is enough to make nanotechnology revolutionary—but only indirectly. Elsewhere, nanomaterials, presently dominated by nanoparticles incorporated into nanocomposites, are already used in a wide range of products, which are either superior to previous versions for the same cost, or offer the same performance for lower cost. Since these products are typically mass consumer items with a global market, such as razor blades or soft drink canisters, their economic impact may be considerable, but they can scarcely be said to be revolutionary. We should spend more time considering those nanotechnologies still being developed, but which will more clearly offer novel possibilities, such as wearable electronics, and miniature, inexpensive and highly efficient fuel cells. The latter will certainly be a great convenience, reducing emissions from vehicles (in comparison to the internal combustion engine) and allowing laptop computers and mobile telephones to be used for days or even weeks before needing to be recharged, but again, as with electronics, the impact of the nanotechnology is indirect. In the first part of this essay the typical assertions of the proponents will be briefly examined. In the second part, some key aspects of nanotechnology’s far reaching possible consequences, which have so far either escaped or received little scrutiny, will be examined.

The Nano/Bio Interface

This chapter is mainly about nanobiotechnology, which is defined as the application of nanotechnology to biology. By far the most important aspect of nanobiotechnology is nanomedicine – the use of nanotechnology to enhance diagnostics and therapy. The final topic of the chapter is nanotoxicology, which is defined as the toxicology of nano-objects. As the volume of production of nano-objects increases with its move from the laboratory into the industrial factory, this topic becomes increasingly important, not only from the point of view of occupational health but also from consideration of the possible exposure of the consumer to nano-objects and the impact of their almost inevitable release into the environment.