Biomedical Engineering Reference
In-Depth Information
monitoring and control of homogeneity and crystallinity/polymorphism. In
addition, Raman spectroscopy is a powerful means to verify the chemical con-
tent downstream during the tablet compression process step. Finally, in the
area of bioprocessing the role of Raman spectroscopy for monitoring and con-
trol is still in an exploratory stage. The few applications demonstrated so far
are mainly related to bioreactor and separation process steps as is discussed
in Section 10.3.
10.3 In-Process Measurement Equipment
In the manufacturing process environment there are a wealth of process con-
ditions and materials' physical states and chemistry that drive the type of
measurement and equipment needed. Typical process monitoring and control
applications using Raman spectroscopy will probe specific characteristics and
can be used for evaluating key attributes of a material or process, be they
static or dynamic. Optimisation of the instrument design and measurement
configuration is critical to the success of a process application. Generally, the
conventional approach for an in-process Raman measurement is based around
a probe that provides both light delivery and Raman scatter collection; this is
clearly a backscatter collection geometry. The probe is optically connected to a
spectrometer via fibre optics. One of the key advantages of this design is sam-
pling flexibility and relative ease of integration into a manufacturing process.
The design of the process measurement then drives the design of the probe
based on process requirements such as immersion vs remote or non-contacting
probe, working distance, dimensions of sampling, speed of sampling.
There are many types of probes that are designed for specific types of
measurement. The important criteria are ecient delivery of the excitation
light to the sample, ecient collection of the Raman scattered radiation and
removal of background responses. Cooney et al. [6, 7] have compared probe
designs for throughput and collection eciency and have modelled sensitiv-
ity and sampling volume. These models are based on transparent samples. In
general, pharmaceutical materials and processes are opaque and highly scat-
tering and therefore, the solution is partly driven by an empirical approach
and is sample dependent.
A simple probe design for backreflection measurements might be a single
light delivery fibre surrounded by an array of collection fibres, so delivery and
collection are effectively on the same optical axis. The probe may have a win-
dow or lens at the end to improve light delivery and collection and to protect
the integrity of the probe. A problem with the use of a fibre-optic-based design
is that a Raman signal can be generated in the delivery fibre by interaction
with the fused silica matrix [8]. This signal can be intense and degrade the
Raman response of the sample. In addition, Fresnel reflected and elastically
scattered light from the sample can be captured by the collection fibre, gener-
ate a Raman response in the fibre and further degrade the signal. Elimination
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