Biomedical Engineering Reference
In-Depth Information
future, the ability to predict the intelligent properties of biomolecules would greatly facili-
tate the design and integration of these biological elements into functioning smart biosen-
sors, without the necessity for performing exhaustive characterization experiments prior
to their use.
1.1.1
Components of Biosensors
In terms of the simplest definition of its components, biosensors are typically thought to
be comprised of a biological element(s) that is usually attached permanently to an under-
lying substrate. These are integrated with an appropriate signal transduction platform that
provides a mechanism whereby the presence and usually the concentration of analyte
being sensed by the biological element is converted into some type of quantitative elec-
tronic signal or output.
1.1.1.1 Biological Elements
The biological elements that have been used in the creation of biosensors vary widely in
type and include proteins (enzymes), nucleic acids—primarily DNA, lipids and mem-
branes, carbohydrates, complexes between these individual components, and living cells.
One may ask what the advantage is of integrating biological elements as opposed to
purely chemical recognition elements into the design of a sensor? A compelling answer is
that in most instances biological macromolecules, the current endpoints of evolution,
provide overall superior properties compared with chemical systems developed to carry
out equivalent functions. In general, nature has designed far better systems for tasks such
as recognition specificity, catalytic efficiency, electron transfer, and other complex inte-
grated functions, than the talented bench scientist is capable of creating with current
design and synthesis approaches. This is the case even where biomimetic studies form a
part of the design process. As we describe in more detail in a later section, biological
macromolecules and their complexes, as well as living cells, possess subsets of or all of the
intelligent properties that we wish to exploit in the design of smart biosensors. However,
there are recognized drawbacks to the use of biological macromolecules in smart biosen-
sors. For one, they tend to be functionally less robust than chemical systems to specific
factors in their environment. These include extremes of pH, temperature, the presence of
oxidizing agents, as well as enzymatic degradation, to name just a few. Another drawback
is that one has been limited traditionally by the function(s) nature evolved into the avail-
able biological systems. However, these stability and functional limitations are currently
being overcome through modern approaches that seek to modify biological macromole-
cules through a targeted design approach. Methods such as Directed Evolution (1,2),
which involve the repeated sequence evolution of existing native proteins coupled to a
criterion-based selection protocol, have provided new approaches for overcoming
nature's design limitations. In fact, not only can stability be enhanced greatly, but also new
function can be evolved through the use of these techniques. This is not a topic we deal
with explicitly in any more detail in this review. But it does represent a type of technical
approach that will result in novel and improved biosensor components in the future.
1.1.1.2 Immobilization Methods
Once the appropriate biological element has been identified and the platform chosen, a
suitable surface attachment strategy must be devised. An effective attachment strategy
should preserve the function and create a stable environment for the biological element,
as well as facilitate and enhance coupling of the signal from the biological element to the
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