Indwelling biosensor for real-time chemotherapeutic blood level monitoring

DESCRIPTION provided by applicant The Specific Aim of this proposal is to test the feasibility of developing a catheter based indwelling biosensor for the real time continuous monitoring of chemotherapeutic blood levels of lung cancer patients A tool that continuously monitors blood drug levels in real time will enable an unprecedented understanding of an individual patientandapos s distinctive metabolism and clearance of drugs This information is critically needed for three reasons to reduce drug dosing related toxicities such as heart tissue damage to potentially improve efficacy of chemotherapeutics by ensuring patients maintain therapeutic drug blood levels and to facilitate development and approval of new drugs with narrow therapeutic ranges and high interindividual variability The proposed tool will measure blood levels of chemotherapeutic drug doxorubicin every seconds in flowing venous whole blood for real time determination of blood levels and accurate calculation of cumulative drug exposure Current methods require multiple timely blood draws that are error prone and require manual labor for both sample collection and laboratory analysis No point of care method is available to detect doxorubicin The proposed work is based upon an existing doxorubicin microfluidic biosensor that works in whole blood for over hours Ferguson et al see Plaxco letter of support We propose to design and fabricate a biosensor that utilizes the advantageous fluidic dynamics of the existing system but that is small enough to fit in an I V catheter in a patientandapos s arm Diagnostic Biochips has already developed a proprietary MEMS process for fabricating implantable multi electrode arrays We will accomplish our Specific Aim by using finite element analysis to model fluid flow in venous flowing whole blood to demonstrate a laminar boundary buffer layer at the sensor interface to prevent biofouling fabricate the optimized catheter design and functionalize the biosensor and develop electronics for point of care use The test of feasibility will be the successful detection of doxorubicin in flowing whole blood for at least hours at physiologically relevant concentrations nM uM Eksborg et al in a device that with clinically implementable design defined by similarity in size and geometry to existing I V catheters and acceptable levels of I V fluid delivered In Phase II we will test our sensors in live animals and using principles of robust design turn our prototype into a commercial product PUBLIC HEALTH RELEVANCE The proposed work will result in a tool that can be used to monitor patient blood levels of chemotherapeutic drugs Through continuous real time data collection the proposed device will reduce toxicity from overdoses and inefficacy from under dosing Diagnostic Biochips already makes implantable biosensors for electrical detection and has the expertise required producing robust commercially viable implantable biosensors for neuroscience and clinical applications End of Abstract