Biomedical Engineering Reference
In-Depth Information
and become activated, further contributing to the clotting process. This can
result in thrombus formation, which poses a potential risk to the patient of
the clot being shed and blocking other blood vessels.
If the sensor is implanted in subcutaneous tissue, as is the case with many
of the glucose sensors discussed above, an acute infl ammatory reaction
occurs, including protein adsorption and leucocyte recruitment. A chronic
infl ammatory reaction follows, involving the recruitment of macrophages,
monocytes and lymphocytes, and culminating in the formation of a fi brous
capsule around the sensor, consisting of macrophages and collagen. The
presence of these cells changes the composition of the surrounding fl uid,
and alters the concentration of the target analyte. For example glucose is
consumed at a faster rate by infl amed tissues.
Various technologies have been investigated with respect to improving
the biocompatibility of implanted sensors. Biomaterials solutions designed
to improve biocompatibility include coatings (hydrogels, blood-compatible
polymers, naturally derived biomaterials, phospholipid-based biomimetic
materials and immobilised drugs) and surface topological modifi cations. A
more active solution that has been widely studied is the release of nitric
oxide.
In vivo,
nitric oxide is released by vascular endothelial cells and
inhibits platelet adhesion and activation.
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As such, it has the potential to
limit platelet activity in response to the implantation of a sensor, and reduce
the triggering of the coagulation cascade. Materials which can mimic such
in vivo
tissue functions have been investigated, including silicone rubber
coatings incorporating NO-donor diazeniumdiolates and polymers which
contain constituents (immobilised Cu(II) complexes or organoselenium)
capable of converting substances present in the blood (nitrosothiols) to
nitric oxide. Such techniques have been shown to reduce clot formation on
catheters measuring
p
O
2
levels, and hence increase the accuracy of the
measurements.
11.5
In vitro
sensors
Some biosensors use biological cells as the sensing element, rather than
molecules such as enzymes or antibodies. These cell-based biosensors
exploit the physiological response of cellular systems to various substances,
including toxins and drugs. Integration of the cell(s) with a sensor of one
of the types discussed above provides an opportunity to derive information
from the changes in cell metabolism and physiology that may be observed.
Cell metabolism can be measured by the combination of the cells of interest
with sensors including pH, oxygen, CO
2
and lactate. These can be an indica-
tor of receptor activation, which can be of use in high-throughput drug
screening.
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Beating cardiomyocytes have formed the basis for a biosensor
for measuring heavy metal toxicity for the study of its effect in the cardio-
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