Biomedical Engineering Reference
In-Depth Information
into the pouches that are subsequently separated by a mechanical sealer
resulting in sealed, sterile samples.
The proprietary Millipore system comprises a port insert that can be fitted
to several bioreactor sideports and a number of flexible conduits that can be
opened and closed individually for sampling and are connected to flexible,
disposable sampling containers. Sampling is limited to the number of avail-
able conduits in each module.
These sampling systems allow aseptic sampling but are limited by the
number of samples taken per module and the lack of automation. And while
these methods come with good validation data, the risk of contamination
cannot be removed since the bioreactor is indeed breached every time a sam-
ple is withdrawn. There is a need to develop other methods that will not
require contact with media.
Optical Sensors
Optical sensors work on the principle of the effect of electromagnetic waves
on molecules. It is an entirely noninvasive method and can provide continu-
ous results of many parameters at the same time. It is relatively easy to use
them through a transparent window in the bioreactors. The detector part
of the system can be physically separated, allowing utilization of expensive
analytical devices allowing optical sensors to be used in situ or online.
Fluorescence sensors can be optimized for measurements of nicotinamide
adenine dinucleotide phosphate (NADPH) and are used for both biomass
estimation and differentiating between aerobic and anaerobic metabolism.
The two-dimensional process fluorometry enables simultaneous measure-
ment of several analytes by scanning through a range of excitation and emis-
sion wavelengths including proteins, vitamins, coenzymes, biomass, glucose,
and metabolites such as ethanol, adenosine-5'-triphosphate (ATP), and pyru-
vate. Thus, it is possible to use fluorometry to characterize the fermentation
process. Generally, a fiber-optic light attached to the bioprocessor and shin-
ing the light through a glass window in the bioprocessor works very well.
An example of this is the fluorometers from BioView system ( www.delta.
dk ) . The BioView sensor is a multichannel fluorescence detection system for
application in the biotechnology, pharmaceutical and chemical industries,
food production, and environmental monitoring. It detects specific com-
pounds and the state of microorganisms as well as their chemical environ-
ment without interfering with the sample. The BioView system measures
fluorescence online directly in the process. An interference with the sam-
ple is eliminated. There is no need to take samples for off-line analysis that
saves manpower and reduces the risk of contamination. However, in view
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