Biomedical Engineering Reference
In-Depth Information
2 Techniques for Bioprocessing Monitoring
2.1 Heat-Flow Biocalorimetry
Bioprocesses are complex systems involving multiple ongoing biochemical reac-
tions at both intra- and extra-cellular levels. According to classical biothermody-
namics ''All living cells involve heat exchange with their surroundings in order to
sustain their cell metabolism''. The heat generated during cell metabolism is due to
dissipation of excessive internal (Gibb's) energy stored inside the living cell. The
amount of heat generated by a living cell is determined by the metabolic activity of
the cell itself. Each living cell sustains the balance between the anabolic and cata-
bolic processes by regulating the amount of heat dissipation and, hence, persists as
metabolically active under different process conditions [
5
]. As a result, the mea-
surement of metabolic heat production should provide valuable information on the
physiological activity of the organism and may be regarded as a 'metabolic variable'
of any bioprocess system. The measurement of metabolic heat has been gaining
attention in both industry and academia due to its non-specific, non-invasive and
insensitive properties in relation to the process systems to which it is applied [
6
-
8
].
2.1.1 Working Principle and Operation
Reaction calorimeters have been especially designed for bioprocess monitoring.
This section deals only with advances concerning bench-scale heat-flow biocalo-
rimeters; related fields such as micro-calorimetry are not discussed here. Several
reports are available which describe the principle of heat-flow biocalorimetry
[
9
,
10
], which is similar to a bench-scale fermenter but with additional calorimetric
sensors for metabolic heat flow rate measurement.
2.1.2 Development of Biocalorimetry
'Biocalorimetry' is an old branch of science that dates back to the eighteenth
century. It facilitates a quantitative interpretation of metabolic heat generated from
living systems as a useful 'process signal' for monitoring purposes [
11
]. Since the
start of the nineteenth century, temperature sensors with improved sensitivity and
sophisticated measurement techniques have become available, and these have been
deployed by several research groups for metabolic heat measurements, rendering
'biocalorimetry' popular among scientists and academics. Micro-calorimeters
were primitive models of biocalorimeters used in the mid-nineteenth century to
effectively monitor fermentation processes [
12
,
13
]. Micro-calorimeters accom-
plished high-sensitivity measurements of heat flow signals; however the technical
difficulties associated with the design, viz. pH control, mixing and oxygen supply,
remained a hurdle for technical applications [
7
]. These technical challenges led to
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