Date of Award

8-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Guiseppi-Elie, Anthony

Committee Member

Latour , Robert

Committee Member

Parrish , John

Committee Member

Vyavahare , Naren

Committee Member

Gao , Bruce Z.

Committee Member

Jauch , Edward C

Abstract

Trauma diagnostics and management are major aims of research for implantable amperometric enzyme biosensor technology. Biosensors are capable of monitoring metabolic variables in a minimally invasive manner and have great potential to augment current wireless vital sign monitoring technologies in order to make a more robust physiologic status monitoring platform. The dual responsive Electrochemical Cell-on-a-Chip Microdisc Electrode Array (ECC MDEA 5037) is a recently developed electrochemical transducer for use in a wireless, implantable biosensor system for the continuous measurement of interstitial glucose and lactate. Hyperglycemia arising from insulin resistance and hyperlactatemia arising from anaerobic metabolism both occur following trauma and hemorrhage. The extent of trauma can be correlated to the magnitude of the hyperglycemic response. Rate of production and final concentration of lactate in both interstitial and blood compartments have also been observed to correlate to various stages and endpoints of trauma. Applying the integrated metabolic response of these analytes to direct lifesaving interventions may decrease mortality and other complications of hemorrhage and shock.
The Pinnacle dual potentiostat (A) and MDEA 5037 biotransducer (B) form a system (C) intended to demonstrate the value of advanced point-of-care diagnostic technology. When configured as an ASIC, this minimally invasive implantable device may be used by first responders to initiate early and continuous monitoring of patient physiologic status. Development of the bioactive membrane and both in vitro and in vivo characterization of the MDEA 5037 have been performed. Using the mediator ferrocene monocarboxylic acid (FcCOOH) as a redox probe, the steady state dose response of the MDEA 5037 was 1.9 times greater than the theoretical response as determined by the Cottrell relationship for multi-disc array electrodes. Electrochemical impedance spectroscopic analysis of the MDEA 5037 fits a standard Randle's equivalent circuit model with error 2, a KMapp of 7.20 (±2.59) mM, an Imax of 76.75 (25.50) μA/cm2, a response time of 16.5 (±5) s, and a detection limit of 0.05 (±0.03) mM. The foregoing use of the p(Py-co-PyBA) co-polymer yielded a fivefold increase in sensitivity (p < 0.001) and a threefold increase in maximum current (p < 0.01) compared to biotransducers fabricated with polypyrrole (PPy) only. A Sprague-Dawley hemorrhage model was instrumented with indwelling biotransducers and externalized wireless potentiostat. Resection after 4 h and subsequent in vitro testing showed a decreased sensitivity from 0.68 (±0.40) to 0.22 (±0.17) μA/mM/cm2 with an average change of 56 (±48) %, and a change in the in limit of detection from 0.05 (±0.03) to 0.27 (±0.27) mM with an average change of 298 (±298) %. Response time of resected biotransducers was 244 (±193) s, 6 times greater than pre-implanted biotransducers with a response time of 41 (±18). This is likely due to biofouling and/or protease related enzyme denaturation. For long duration implantable devices an electroconductive hydrogel has been developed to confer its antifouling properties. In addition to mitigating inflammation and fibrous encapsulation, these hydrogels maintain the stability of the enzymes far more effectively when compared to system fabricated with just polypyrrole and show increasing sensitivity during storage for up to 21 days.

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