Environmental Engineering Reference
In-Depth Information
while light absorbance, light scattering, or a combination of the two provide optical
indications of cell mass [31].
Carbon dioxide, a waste product of cell respiration, is an important indicator of bioreactor
status and can be measured on-line by means of sterilizable electrode sensors, optical sensors,
and sensors based on gas permeation through selective polymer membranes [32, 33], serving
as the basis for process control loops [33].
Several spectroscopic techniques are also available to quantify the presence of numerous
organic and inorganic species simultaneously, due to recent advances in optics and
computing. An example is shown in Figure 3, in which a noninvasive sensor has measured
the whole-cell biotransformation of L-serine and indole to tryptophan [34]. This approach is
also applicable to the processing of sugar beet molasses at an industrial scale [35]. Glucose,
fructose, glutamine, ammonia, CO2, and phosphate are among the many compounds that can
be measured by either near or mid-infrared spectroscopy. Recent developments of improved,
low-cost optical sensors are also promising [27, 36, 37]. Further development for
miniaturization, improved robustness, and sensitivity are expected [38, 39].
A separate approach is based on the attachment of the gene for green fluorescent protein
onto a protein of interest present during manufacture [40]. This is particularly attractive if the
tagged molecule is the product of interest, such that product concentration can be measured
directly. A number of other color probes are also currently available, opening a promising
avenue for real-time monitoring of the expression of multiple genes simultaneously [41].
Improved real-time sensing of bioreactor conditions is essential to model validation and
process control during operations, and future bioreactors are expected to be massively
instrumented to provide detailed real-time information of vital interest.
Figure 3. Two-dimensional fluorescence spectra of a fermentation broth [34].