| Background:
Following injury that results is tissue hypoxia, interstitial lactate
levels increase and are the main source of metabolically-produced acid
responsible for tissue acidosis. Lactate levels have also been found to
correlate with the severity of injury, including hemorrhage. Small
molecules such as lactate and glucose exists in equilibrium between the
interstitial and vascular compartments when systemic levels are
elevated. Interstitial levels of lactate should thus be reflective of
systemic levels when whole body tissue hypoxia occurs such as in
hemorrhage. The ability to monitor in vivo lactate in the interstitium
is possible but current methods are either not clinically feasible for
prolonged measurement or are unreliable because they suffer from
deleterious effects of endogenous interferences and fouling. |
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Objective:
Our goal is to develop an implantable lactate-sensing biochip for
temporary implantation and capable of telemetered reporting of local
lactate levels as well as local glucose levels. These biochips will be
temporarily injected/implanted into a skeletal muscle bed such as the
deltoid muscle of rats. Lactate levels will be continuously monitored
for implantation periods varying from several hours to 3 months. This
will include testing of the sensor in a model of severe hemorrhagic
shock with comparison of sensor-recorded levels of lactate to systemic
levels of lactate and whole body oxygen debt. A suitable MEMS antenna
will be developed and demonstrated in parallel. Study Design:
Microlithographically fabricated biochip substrates adopting a dual
"microbore" working electrode design will be constructed. We
hypothesize that the biosensor membrane, fabricated from our previously
demonstrated bioactive hydrogel composite polymer will confer enhanced
interferent rejection properties and impart bioactive biocompatibility
to these biochips. |
| The
lactate-sensing membrane and the biochip substrate will be integrated
into sustainable in vivo packaging for subcutaneous implantation in rat
models including one of severe hemorrhagic shock. A BioMEMS telemeter
device will be developed that will be integrated with the biosensor for
telemetric reporting of lactate levels. |
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Relevance:
The design, fabrication and deployment of implantable biosensors for
the continuous in vivo monitoring of physiological analytes present
many challenges. Among these are interference shielding,
biocompatibility, and stability of the biorecognition layer. A sensor
that can continuously monitor lactate concentrations, unchallenged by
these hindrances, will be extremely useful for injured war-fighters on
the battlefield. Systemic lactate levels and base-deficit levels have
been demonstrated to serve as predictors of survival during severe
trauma. The ability to continuously monitor lactate levels and thus
cumulative oxygen debt in austere battlefield environments and its many
echelons of care may improve the ability to triage casualties and to
allocate valuable resources. |
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