Medical Device Link.

DESIGN

Composition

Image: iStockphoto

Biosensors are detection devices that comprise a biological component of some type combined with a nonbiological element that converts the detection by the biological component into a measurable signal. They usually comprise the following components.

• A biological element. This can be a tissue, cell(s), subcellular components such as organelles or receptors; a microorganism; biomolecules such as nucleic acids, antibodies, proteins or enzymes; biologically derived materials such as recombinant antibodies; engineered proteins and aptamers; or biomimetic materials such as synthetic catalysts, combinatorial ligands and imprinted polymers
• A transducer. This can be electrochemical, piezoelectric, magnetic, optical, thermal, acoustic or some other system capable of transforming the signal that results from the interaction between the biological component and the sample under study into another signal, for example, electrical, optical or mechanical that can be more easily measured by conventional means.
• Associated systems. These include electronic systems, IT and software that can process and display the resulting signals.

Increasingly, biosensors are exploiting the nanoscale interactions between the biological detector and the test sample, and between the biological and nonbiological components of the system to produce novel systems that are capable of extreme miniaturisation and of providing highly specific results.

The concept of biosensors is not new, and began in the early days of mining with caged birds such as canaries being used to give advance warning of toxic gases. A widely known, and by far the most studied, class of biosensor that has been developed over recent decades is the portable glucose monitor for use by diabetics. Most forms of this employ the enzyme glucose oxidase as their biological component and an electrode as their transducer. Because of the increasing incidence of diabetes throughout the developed world and the ever increasing need for devices that are patient friendly and capable of being adapted to individual needs, this remains one of the most intensive application areas for biosensor development.

Applying nanotechnology to improve biosensors

The application of knowledge at the nanoscale can bring a new degree of functionality to biosensors because many of the entities being detected themselves possess nanoscale features. There follows just a few of a rapidly growing number of examples of biosensors that incorporate nanoscale engineering.

Magnetic immunosensor

In an affinity biosensor, the affinity reaction between the receptor such as antibodies or cell receptors, and a target molecule such as antigens or ligands is detected. Accumulation of target molecules leads to a measurable change at transducer level in real time. One recent label for these affinity assays are paramagnetic nanoparticles and, in addition to the ability to monitor binding reactions, these offer the possibility to store data magnetically and provide a permanent record rather like recording tape; one example of this technology is the magnetic immunosensor.

Resonating beam sensors

These sensors work on the principle of tiny vibrating beams whereby any object adding mass to the beam will alter the frequency of oscillation. Microfabrication techniques, as used in the computer chip industry, allow the construction of minute cantilever structures whose oscillation can be detected using lasers or a piezoelectric element. The frequency of oscillation is affected by any mass on it. Researchers at Cornell University (Ithaca, New York, USA) have managed to detect biological materials down to a few attograms (10–18 g) using an optical waveguide displacement sensor developed from this principle, and the detection of single molecules or bacteria is possible.¹

Plasmon surface resonance sensor

In this type of biosensor, the sensing system is based round the principle of surface plasmon resonance in which incident light is directed, for example, by a prism onto a nanometallic gold or silver film where it creates an evanescence field that emits surface plasmons that can be detected. By grafting different molecularly imprinted polymer coatings onto the surface of the gold or silver, the surface plasmon resonance is altered so that the biosensor can become specific for different biomolecules. One biosensor of this type has been recently developed by researchers at the University of Washington (Seattle, Washingon, USA) for the detection of the neurotoxin domoic acid associated with amnesic shellfish poisoning.²

Nanowire arrays

Nanowires formed from silicon, carbon nanotubes or polymers are being increasingly used in biosensors, for example,

• silicon based nanowire arrays can be used to test nanolitre quantities of blood for a range of biomarkers
• single nanowires can probe individual cells
• nanowires can also be used as a basis for electrical communication with single enzyme molecules
• polymer nanowire arrays are showing promise as the basis for minimally invasive sampling.

Ion channel biosensors

The transport of different molecules through pores in biological membranes such as the ion channels in cell membranes is of major biological importance. These channels have important properties, including gating and selective permeability. A number of biosensors are being developed that incorporate this principle, for example,

• an analyte may be captured by tethered antibodies that are bound to gramicidin molecules that form part of an ion channel; when this channel opens, cations flow through it and can be detected by an underlying gold electrode; this system is capable of detecting lower than picolitre concentrations of analyte³
• carbon nanotubes (CNTs) in which the ends of the CNTs have functional groups attached at each end such as CH₂-COO and CH₂-NH₃; these have been used to simulate a real ion channel and have potential biosensing applications.⁴

Functionalised materials and biomimetic approaches

Multiwalled carbon nanotubes (MWCNTs) possess a range of useful electrically conductive and other important physical properties and are showing promise as novel high surface area electrodes capable of sensing biological redox reactions. For example, MWCNTs may be functionalised by adding a hyperbranched polymer coating, which incorporates ferrocene groups as the detection system.

Surface features that mimic natural biological recognition sites may be created by a variety of nanoscale approaches. Proteins may be nanopatterned onto a gold surface by direct surface imprinting and then the surface polymerised following which the proteins are removed leaving imprinted patterns that can be used to detect similar proteins. Alternatively, a protein nanopatterned surface may be used as a template to print patterns that are capable of recognising that protein onto another polymerised surface in a process known as microcontact surface imprinting.

Another process uses an atomic force microscope tip to scrape away desired recognition patterns on a protein resistant self-assembled monolayer (SAM) on a gold surface. New protein binding SAM molecules are then immobilised onto the treated surface in a process known as nanografting, and target proteins such as haemoglobin can then bond to the new grafted biosensing surface.⁴

A wide range of artificial recognition surfaces can be obtained using molecularly imprinted polymers in which crosslinked polymers self-assemble around a molecule that acts as a template. This molecule is subsequently removed leaving an imprint containing functional groups complementary to those of template in the polymer.

Future trends for nanobiosensors

The ability to engineer features at the nanoscale provides huge scope to integrate biological or biologically derived molecules into sensing systems or to design features that can recognise target molecules in a biomimetic manner. These systems are capable of high specificity using low concentrations of analyte. This opens up the possibility of “smart” diagnostic and monitoring systems that can be implanted and, for example, coupled to drug delivery systems that respond to minute changes in physiology or metabolism for future noninvasive diabetes monitors; or that respond to the presence of low levels of pathogens or other clinically important markers, which facilitates the possibility of highly personalised medical treatments. Biosensors of this type also have a promising future in a wide range of environmental, food and security testing and monitoring applications.

Richard Moore is Manager, Nanomedicine and Life Sciences, at The Institute of Nanotechnology, Suite 5/9 Scion House, Stirling University Innovation Park, Stirling FK9 4NF, UK, tel. +44 1786 458 020, e-mail: richard.moore@nano.org.uk www.nano.org.uk, www.nanomednet.org