Biomedical Engineering Reference
In-Depth Information
that are under development. They are used for the functional characterization and
high-throughput drug discovery or detection of pathogens, toxics, and odorants
and clinical diagnostics. Unlike other biosensors such as nucleic acid or antibody-
based sensors, cell-based biosensors are not specific for certain compounds but
are capable of responding to a wide range of biologically active compounds and
offer the potential to gather greater information content than biomolecular-based
sensors.
To be used as a biosensor, the cellular signal generated in the transducer needs
to be determined in a noninvasive manner. Electrically excitable cells such as neu-
rons and cardiomyocytes are particularly useful in this sense, since the activity of
cells can be monitored by the extracellular recordings using microelectrodes. For
electroanalytical measurements and biosensing, electrode and biosensor devices
can be miniaturized down to a cell-size scale using microfabrication technology
and can be positioned directly at the vicinity of the cell surface, where cellular sig-
naling substances are captured before they diffuse. In the case of biosensors, highly
sensitive in situ monitoring can be performed. Although quantitatively the signal
is very small, it is enhanced through either circuit amplifiers or catalytic reactions
on the biosensor. Cell-based biosensors may have a longer response time and less
specificity to a single analyte of interest due to the presence of other enzymes in
the cells.
Many nonexcitable cell types are used for the detection of various classes of
materials that do not react with the excitable cells. Transducers could be optical
instead of electrical. Immune cells and hepatocytes are good examples of nonexcit-
able cells used for cell-based biosensors. For example, hepatocytes have been used
to assess and predict the effects of toxicants. Many compounds do not result in
immediate response or toxicity. In this case, cell motility and adhesion can be also
used as a cellular signal. Genetically engineered cells that recognize and report the
presence of a specific analyte have also been developed. Cells are produced with a
nucleic acid sequence in which genes that code for luciferase or galactosidase en-
zymes are placed under the control of a promoter that recognizes the analyte of in-
terest. Because the organism's biological recognition system is linked to the report-
ing system, the presence of the analyte results in the synthesis of inducible enzymes
which then catalyze reactions resulting in the production of detectable products.
Many micro-organism-based biosensors are used for assessing toxins, as they
are less expensive to construct relative to other cell types. Furthermore, micro-
organisms are more tolerant of some assay conditions that would be detrimental to
an isolated protein as micro-organisms have mechanisms to regulate their internal
environment based on external conditions. Micro-organism-based biosensors are
based on using the analyte either as a respiratory substrate or as an inhibitor to
the respiration. Biosensors that detect biodegradable organic compounds measured
as biological oxygen demand (BOD) are the most widely reported micro-organ-
ism-based biosensors using this mechanism. The general limitations of cell-based
biosensors are the long assay times, including the initial response and return to
baseline.
