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An implantable biochip to influence patient outcomes following trauma-induced hemorrhage

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Abstract

Following hemorrhage-causing injury, lactate levels rise and correlate with the severity of injury and are a surrogate of oxygen debt. Posttraumatic injury also includes hyperglycemia, with continuously elevated glucose levels leading to extensive tissue damage, septicemia, and multiple organ dysfunction syndrome. A temporary, implantable, integrated glucose and lactate biosensor and communications biochip for physiological status monitoring during hemorrhage and for intensive care unit stays has been developed. The dual responsive, amperometric biotransducer uses the microdisc electrode array format upon which were separately immobilized glucose oxidase and lactate oxidase within biorecognition layers, 1.0–5.0 μm thick, of 3 mol% tetraethyleneglycol diacrylate cross-linked p(HEMA-co-PEGMA-co-HMMA-co-SPA)-p(Py-co-PyBA) electroconductive hydrogels. The device was then coated with a bioactive hydrogel layer containing phosphoryl choline and polyethylene glycol pendant moieties [p(HEMA-co-PEGMA-co-HMMA-co-MPC)] for indwelling biocompatibility. In vitro cell proliferation and viability studies confirmed both polymers to be non-cytotoxic; however, PPy-based electroconductive hydrogels showed greater RMS 13 and PC12 proliferation compared to controls. The glucose and lactate biotransducers exhibited linear dynamic ranges of 0.10–13.0 mM glucose and 1.0–7.0 mM and response times (t 95) of 50 and 35–40 s, respectively. Operational stability gave 80% of the initial biosensor response after 5 days of continuous operation at 37 °C. Preliminary in vivo studies in a Sprague–Dawley hemorrhage model showed tissue lactate levels to rise more rapidly than systematic lactate. The potential for an implantable biochip that supports telemetric reporting of intramuscular lactate and glucose levels allows the refinement of resuscitation approaches for civilian and combat trauma victims.

Schematic of an electrode-supported, two-layer hydrogel membrane for bioreceptor hosting and tissue biocompatibility

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Acknowledgments

This work was supported by the US Department of Defense (DoDPRMRP) grant PR023081/DAMD17-03-1-0172, by the Consortium of the Clemson University Center for Bioelectronics, Biosensors and Biochips (C3B), and by ABTECH Scientific, Inc.

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  1. Center for Bioelectronics, Biosensors and Biochips (C3B), Clemson University Advanced Materials Center, 100 Technology Drive, Anderson, SC, 29625, USA

    Anthony Guiseppi-Elie

  2. Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, 29634, USA

    Anthony Guiseppi-Elie

  3. Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA

    Anthony Guiseppi-Elie

  4. Department of Electrical and Computer Engineering, Clemson University, Clemson, SC, 29634, USA

    Anthony Guiseppi-Elie

  5. ABTECH Scientific, Inc., Biotechnology Research Park, 800 East Leigh Street, Richmond, VA, 23219, USA

    Anthony Guiseppi-Elie

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Guiseppi-Elie, A. An implantable biochip to influence patient outcomes following trauma-induced hemorrhage. Anal Bioanal Chem 399, 403–419 (2011). https://doi.org/10.1007/s00216-010-4271-x

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