Exploring Key Design Parameters Exploited by Naturally Occurring Chemoperception Systems

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We have recently demonstrated the ability to measure specific small molecules (here the cancer chemotherapeutic doxorubicin) continuously and in real time in a flowing stream of whole blood. Achieving this requires not only the ability to detect specific molecules without the use of added reagents or washing steps, but also a sensor that is rapidly reversible and is selective enough to work even in highly complex sample matrices. The availability of such a technology could vastly improve our ability to monitor soldier health/physiological status, to perform environmental monitoring, and to monitor industrial processes.

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Our goal is to mimic biology’s ability to continuously and quantitatively monitor specific molecules directly in complex, flowing samples, such as the continuous monitoring of hormones, metabolites, etc in flowing blood or environmental contaminates in an effluent stream. To achieve this we are developing several integrated and complementary technologies based on naturally occurring counterparts. These are: 1) conformation-linked signaling, which provides a means of transducing binding events into specific, not-easily-fooled output signals, 2) the adaptation of naturally-occurring regulatory mechanisms to improve the sensitivity of our sensors to small changes in the concentration of their target molecules, and 3) differential measurements for background correction and gain control. Our ultimate goal is to develop biosensors capable of real-time measurements of multiple biomolecules directly in living animals.



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