Biomedical Engineering Reference
In-Depth Information
several other chapters of this topic, nanoscale assemblies have resulted in the develop-
ment of a wide variety of biological and biologically modified receptors for sensor recog-
nition, as well as provided unique methods of signal transduction capable of sensitively
detecting analytes in the smallest of environments. Employing these new developments,
the fields of chip-based sensing (i.e., biochips, etc.) and nanosensing have seen a recent
explosion of research.
1-11
The small-size scales of these sensors and their ability to probe
previously inaccessible samples, and locations within those samples with a high degree of
spatial resolution, have opened a great many doors in a variety of different fields. While
such sensors have been applied to samples as widespread as embryos
12
and micropores in
synthetic structures,
13
perhaps one of the most dramatically impacted areas of scientific
research has been the field of cellular analyses. Owing to the small-size scale of these sen-
sors, and the often noninvasive nature of the signal transduction technique employed,
they have been able to probe individual living cells, both extracellularly and intracellu-
larly for various lengths of time, providing the first true measurements of cellular path-
ways and metabolic processes without the potential variability experienced from multicell
averaging. Employing nanosensors and biochips (e.g., gene chips), cellular analyses rang-
ing from medical diagnostics
14-16
to the decoding of the human genome
9,17,18
have been
reported. This chapter will provide a highlight into some of the major achievements in
these fields over the last two decades.
Because of their potential for providing an enhanced understanding of cellular
responses to various stimuli, several reviews have already been devoted to the subject of
optical nanosensors and biochips, despite their short existence.
1-4,19-21
This chapter will
provide a look at the evolution of biochips and nanosensors from the beginning to the
present (biosensors capable of probing subcellular compartments of individual cells) and
discuss their application to biological measurements, as well as future directions in
nanosensing. On account of the vast number of publications in this field over the last few
years, this chapter is not meant to provide a comprehensive review, but a critical review
of optical-based nanosensors and biochips, describing significant achievements and
advancements that have occurred in these fields.
Biosensors, generally defined, are devices that consist of a bioreceptor and a signal trans-
duction mechanism capable of producing a measurable signal in the presence of an analyte
of interest. A bioreceptor is a biochemical species (e.g., an antibody, an oligonucleotide, and
an enzyme) or a living biological system (e.g., cells, tissue, or whole organisms) that utilizes
typical biochemical recognition mechanisms (e.g., lock-and-key fit) for analyte recognition.
Upon interaction of the analyte with the bioreceptor the transducer converts the resulting
change into a measurable signal (e.g., optical emission, and electrical current). Figure 3.1
illustrates the conceptual principle of the overall biosensing process.
Owing to the wide array of biosensors that exist, they are often classified into different
categories based upon either the transduction method that they employ or the type of bio-
logical receptor used to provide specificity. Common classes of signal transduction
techniques include (1) optical measurements (i.e., luminescence, absorption, and surface
plasmon resonance); (2) electrochemical measurements; and (3) mass-sensitive measure-
ments (i.e., surface acoustic wave, and microbalance). Bioreceptor-based classification of
biosensors also involves several different categories, with the most common forms of
biorecognition being (1) antibody or antigen interactions, (2) nucleic acid interactions, (3)
enzymatic interactions, (4) cellular interactions (i.e., microorganisms and proteins), and (5)
interactions using biomimetic materials (i.e., synthetic bioreceptors). These bioreceptors
are generally contained in a biosensitive layer doped with the bioreceptor molecules or
covalently attached to the surface of the sensor. When several transducers or
transducer-bioreceptor combinations are arrayed onto individual integrated circuit
microchips, these biosensors are often referred to as biochips. In general, biochips consist
