A sensor system was proposed that would monitor spaceflight bioreactor parameters. Not only will this technology be invaluable in the space program for which it was developed, it will find applications in medical science and industrial laboratories as well.
Using frequency-domain-based fluorescence lifetime technology, the sensor system will be able to detect changes in fluorescence lifetime quenching that results from displacement of fluorophore- labeled receptors bound to target ligands. This device will be used to monitor and regulate bioreactor parameters including glucose, pH, oxygen pressure (pO2), and carbon dioxide pressure (pCO2). Moreover, these biosensor fluorophore receptor-quenching complexes can be designed to further detect and monitor for potential biohazards, bioproducts, or bioimpurities.
Biosensors used to detect biological fluid constituents have already been developed that employ a number of strategies, including invasive microelectrodes (e.g., dark electrodes), optical techniques including fluorescence, and membrane permeable systems based on osmotic pressure. Yet the longevity of any of these sensors does not meet the demands of extended use in spacecraft habitat or bioreactor monitoring. It was therefore necessary to develop a sensor platform that could determine not only fluid variables such as glucose concentration, pO2, pCO2, and pH but can also regulate these fluid variables with controlled feedback loop.
To accommodate the inevitable failure of sensing elements, a biosensor array must be noninvasive and interchangeable — something missing in the current state of the art. Robust, compact, in-situ biosensor arrays that are easy to use and self-contained are needed for the onboard testing and monitoring of bioreactor parameters. In a miniaturized frequency- domain lifetime fluorescence (fLF) system, sensor arrays can be inte-grated into a “dead leg” where the desired assays of bioreactor constituents can be analyzed and results can be sent to a feedback control of regulatory valves that will release nutrients and maintain a constant bioenvironment for cell or tissue culture growth.
The sensor array and dead-leg test solution must be designed so that they are interchangeable for the inevitable requirement of sensor replacement. This design will take into account sterilization considerations as well as the ease with which a part can be replaced in order to minimize the use of astronaut time. The dead leg will allow a small volume of sample to be directed over the fLF sensor surface in order to collect multicomponent emissions and analyze them for different constituents. The biosensor system will also contain feedback controls to the feed lines of the bioreactor, thus providing autonomous operation.
The final fLF sensor system will contain a fully optimized sensor array that can be interfaced with the dead leg of a bioreactor or bioenvironment where current fLF analysis can be performed repeatedly and then replaced when sensor failure occurs. The fLF has a proven track record and the small dimensions needed to accommodate removable and interchangeable interfacings with the bioreactor/bioenvironment. Scientists believe that an even smaller dimension system can be developed for interfacing directly with the bioreactor. This sensor platform, which will be built around this dead-leg sample analysis segment, will be used for preflight testing/evaluation as a solution to bioreactor environment control and will also be marketed in a development program for use in bioreactor control in the biopharmaceutical and medical industries.
The development of this multi-analyte biosensor system has broad commercial applications in the biopharmaceutical industry where genetically engineered drugs are produced by bioreactors. In addition to its use for bioreactor monitoring, this fLF biosensor technology will be useful for biosensor applications including detection of toxins, dangerous chemicals, and hazardous environmental agents. In addition to monitoring bioreactor parameters during long spaceflights of the future, this system can be used to monitor for biohazards to ensure astronaut safety.
This work was done by Mike Mayo, Steve Savoy, and John Bruno of Systems & Processes Engineering Corporation for Johnson Space Center. For further information, contact the Johnson Technology Transfer Office at (281) 483-3809. MSC-23032.