Update on Implantable Sensors for Metabolic Monitoring

Progress has been made toward realizing surgically implantable electrochemical-sensor arrays.

Progress has been made in a continuing effort to develop surgically implantable, biocompatible electrochemical- sensor arrays for continuous measurement of concentrations of analytes that play major roles in human and animal metabolism. This development at an earlier stage was described in "Implantable Electrochemical Sensors for Metabolic Monitoring" (ARL-0017), Defense Tech Briefs, Vol. 1, No. 4 (August 2007), page 28. To recapitulate: in the electrochemical-monitoring approach followed in this development effort, cyclic voltammetry, amperometry, squarewave voltammetry, or a combination of these techniques is used to measure the rate of catalytic oxidation of glucose by the enzyme glucose oxidase (GOX) in a reaction mediated by poly[vinyl pyridine Os(bipyridine)2Cl]- co-ethylamine (POs- EA), which is an osmium-based polycationic redox polymer. To ensure biocompatibility, the GOX is entrapped in a poly(ethylene glycol) diacrylate (PEGDA) hydrogel that has previously been demonstrated to be biocompatible.

Concentrations of Glucose in Blood in a rat were measured by use of a commercially available glucose meter and a blood glucose sensor of the type described in this article. The up arrows indicate glucose injections; the down arrows indicate insulin injections.
Fabrication of a sensor array of the present developmental type begins with the formation of microdisk electrodes and associated conductors in gold film on a flexible polyimide sheet by use of established deposition and photolithography techniques. The microdisk electrodes are functionalized with a monolayer of 11-mercaptoundecanoic acid (MUA) then coated with POs-EA, which adheres by strong electrostatic attraction to the MUA. The POS-EA layer is further coated with a mixture comprising PEGDA, a solution containing GOX, and a photopolymerization initiator. Exposure to ultraviolet light causes cross-linking of the PEG-DA to form the PEG-DA hydrogel that encapsulates GOX.

The effort at the time of reporting the information summarized in the cited prior article was oriented particularly toward developing sensors for monitoring one analyte — glucose — to enable improved treatment of diabetic patients. At that time, it was planned to extend the effort to the fabrication and testing of sensors for monitoring lactate and pyruvate and, eventually, to implement the concept of a single array that contains sensors for monitoring glucose, lactate, and pyruvate. The progress reported since then has consisted mainly of the following:

  • In tests in which glucose sensors were implanted in rats, tracking of blood glucose concentrations in a limited physiological concentration range was demonstrated (see figure); and
  • Lactate and pyruvate sensors were fabricated and tested in vitro.

This work was done by Michael V. Pishko of Pennsylvania State University for the U.S. Army Medical Research and Materiel Command.



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Update on Implantable Sensors for Metabolic Monitoring

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Defense Tech Briefs Magazine

This article first appeared in the June, 2008 issue of Defense Tech Briefs Magazine (Vol. 2 No. 3).

Read more articles from the archives here.


Overview

The document is a final report on the project titled "Microfabricated Multianalyte Sensor Arrays for Metabolic Monitoring," conducted by Dr. Michael V. Pishko at Pennsylvania State University, covering the period from August 15, 2004, to August 14, 2007. Funded by the U.S. Army Medical Research and Materiel Command, the project aimed to develop advanced sensor technologies for real-time metabolic monitoring, particularly focusing on glucose and lactate levels.

The report outlines the fabrication of glucose sensor arrays on gold electrodes using flexible polyimide sheets. The sensors were created through a process involving the cross-linking of glucose oxidase and redox polymers via UV-initiated free radical reactions. The methodology included conventional silicon fabrication techniques, such as mid-UV photolithography, to create five-element array microdisks. Active glucose oxidase was immobilized within photochemically polymerized hydrogels, allowing for effective entrapment on the array electrodes.

The performance of the fabricated microarray sensors was evaluated using cyclic voltammetry, demonstrating individual addressability and minimal cross-talk between adjacent elements. The sensors exhibited a linear response within the biological range, making them suitable for practical applications in metabolic monitoring. Additional electrochemical methods, including amperometry and square wave voltammetry, were employed to further assess the sensors' capabilities.

The report also discusses lactate sensors and their design, as well as the results of animal testing conducted to validate the effectiveness of the sensor arrays. Key research accomplishments and reportable outcomes are highlighted, showcasing the potential impact of these technologies on clinical and military applications.

In conclusion, the document emphasizes the significance of developing reliable, real-time monitoring systems for metabolic parameters, which can enhance patient care and operational effectiveness in military settings. The findings contribute to the broader field of biosensors and metabolic monitoring, paving the way for future research and development in this critical area. The report is approved for public release, ensuring that the knowledge gained can be shared with the scientific community and beyond.