Biomedical Engineering Reference
In-Depth Information
design consisting of a central fiber carrying the excitation beam surrounded
by a circle of collection fibers; these collection fibers could then be realigned
along the slit of the spectrometer to maximize light input while still retain-
ing optical resolution [25]. By being able to physically connect these fibers
to the spectrometer, most of the beam pointing inconsistencies of the open-
path systems have been eliminated. Numerous probes are commercially avail-
able for in situ monitoring based on this or similar designs, which essentially
replicate the original open-beam collection strategy of a tightly focused ex-
citation spot with only minimal depth of field and working distance from
the tip of the probe. Optics is also now typically integrated into the fiber
probe to filter out the laser line and any Raman signal arising from the sil-
ica in the fiber. Although glass is not a very strong Raman scatterer, be-
cause the path length through the fiber is long compared to the measure-
ment volume, and much of the signal generated in the fiber will be internally
reflected along with the laser, the resulting laser output at the sensor end
of the fiber can be significantly contaminated with contributions from sil-
ica Raman bands. These are easily removed using a notch filter; however,
this means that most integrated fiber probes are dedicated to a single laser
wavelength.
The short working distance, high NA sampling configuration is ideal for
measuring liquids or powders, where the presentation of the sample to the
probe is fixed and consistent. However, it fails for solid samples that can-
not be brought close to the probe, have uneven surfaces, or whose posi-
tion cannot be controlled accurately. It should be noted that many of the
biomedical and pharmaceutical applications in this topic would fall into this
category.
Subsequent increases in the size of the collection bundle have improved col-
lection eciency, allowing increased laser spot size, longer working distance,
and increased depth of field [26]; this increased depth of field allowed con-
tributions from subsurface scattering to be collected, which previously would
have been spatially rejected. Although it was known that scattering occurred
within the sample, no concerted attempt to capture this light was made,
since the emphasis had always been on collecting signal very eciently from a
very tightly focused beam. These probes have been instrumental in enabling
online solids measurement in pharmaceutical applications such as content uni-
formity of tablets [27], polymorph quantitation [28], and mixing homogeneity
[29]. The natural development of this large-bundle collection strategy was to
then parse the contribution of the signal at the edge of the bundle from that
at the center; this led to the determination that sample depth-profiling in
a scattering sample could be performed with a single bundle measurement,
a technique now known as SORS (spatially offset Raman spectroscopy; see
Chapter 3) [30]. All of these fiber techniques have been instrumental in en-
abling many of the in vivo and in situ studies described elsewhere in this
text.
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