Monitoring Biomarkers for Muscular Atrophy Using Nanoelectronic Chip for Astronaut Health

POSTDOCTORAL FELLOWSHIP

Skeletal muscle atrophy is a serious health problem for astronauts in long-duration spaceflight under microgravity conditions. Current preventative measures and treatments against muscle atrophy require intense exercise and dietary regimens. Preemptive measurements during the onset of muscle atrophy have the potential to streamline these regimens, decreasing their daily footprint and increasing the quality of life for astronauts. The objective of our proposed project is to (1) develop a fully integrated disposable nanoelectrode array chip (with the size of a stamp) that can be interfaced with a handheld electronic system for simultaneous detection of the a panel of biomarkers to monitor the progression of skeletal muscle atrophy due to disuse under microgravity in long-duration spaceflights; and (2) use such quantitative information to guide the combined countermeasures of physical exercise and pharmaceuticals (i.e., specific protease inhibitors) so that the intensity, duration, and frequency of exercise can be reduced.

The target biomarkers for this research is enzymatic proteases. These proteases have shown to be overexpressed for many illnesses including cancer, human immunodeficiency virus (HIV) and muscular atrophy, and operate by cleaving peptide sequences, effectively destroying critical biological proteins, such as muscle tissues. Monitoring protease biomarkers can serve as a critical early diagnostic tool for conditions specific to long term travel in microgravity. Several key factors currently limit similar healthcare diagnostics during long duration spaceflights. Instrumentation must have a small footprint, minimal power consumption and must be simple enough for untrained users to operate without accurately. Electrochemical sensors, such as the blood glucose monitor, have shown to be robust with a small instrumental footprint. To further decrease this footprint, we will use nanopatterned chips integrated to a microfluidic system to decrease the required amount of sample, minimizing the impact on the user.

We will use this nanopatterned sensor to profile protease biomarkers known to be relevant to muscular atrophy and test the technique in analogs for human urine. To facilitate these measurements, we will use electrodes decorated with carbon nanofiber arrays, which have been previously shown to function in complex biological media. This approach to sample collection and measurement will allow for non-invasive sample collection and will remove the need for additional chemical reagents, further decreasing the footprint of the technique. Additionally, we will use this method to demonstrate the effectiveness of protease inhibitors, which may potentially serve as pharmaceutical treatments, further decreasing the need for extensive exercise regimes and dietary restrictions.

Skeletal muscle atrophy is among the most serious physiological concerns for long-term space travel and habitation. Countermeasures for muscle atrophy in microgravity conditions include exercise regimens, which can last up several hours per day. Daily monitoring of muscle atrophy progression has the potential to guide exercise regimens and pharmaceutical interventions to reduce the impact on daily life, potentially improving efficiency as well as crew morale.

The atrophy process involves a decrease in the rate of muscle cell protein synthesis accompanied by an increase in the rate of protein degradation and apoptosis of various muscle components. Protease enzymes are key to the degradation of existing muscle tissue. Consequently, an early indicator of the onset of physiological muscle atrophy processes is increased activity of protease enzymes. A protease sensor will drastically improve capabilities for crew health monitoring by allowing real-time assessment of muscle atrophy progression and providing a framework for personalized countermeasures.

Current techniques for monitoring proteases can only measure one protease at a time and require extensive sample processing in a laboratory environment. Most of these techniques detect the combined concentration of active and inactive proteases, which may not accurately represent physiological performance of the protease. This limitation can be addressed by measuring the activities of the protease enzymes, which accounts for reactivity and concentration of a specific protease.

Keeping this goal in mind, we have developed a multiplexed gold microelectrode array sensor for quantifying protease activity. We have subsequently demonstrated this sensor’s applicability for multiplex detection of protease activity. We have developed hardware, fitting algorithms, and data processing scripts to demonstrate the multiplexing capabilities of this sensor array and the accompanying assay. Results and data processing can be obtained in less than one hour with minimal sample processing.

This sensor can be used to establish a baseline for protease activity for an individual. Once the baseline has been established, continuous monitoring will be able to detect increases in protease activity prior to the molecular breakdown of muscle tissue. Furthermore, the resulting data can be used to guide preventative measures and treatments; thereby, reducing the risks to long term space habitation. We anticipate that the application of this technology will improve astronaut health, quality of life and, importantly, crew morale.

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