I-Corps: Cell-free Biosensors

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The broader impact/commercial potential of this I-Corps project is the development of a platform to isolate and measure activity of transmembrane proteins (TMPs). Transmembrane proteins are one of biology’s most powerful sensing elements as they can detect nearly any chemical or biological compound. For this reason, they are highly sought after for both detection and development of new therapeutics. Roughly 60% of all drug candidates are targeted against transmembrane proteins, including targets such as viral, pain, and immune receptor proteins. Unfortunately, TMPs are challenging to study and use. Currently, scientists and engineers working with transmembrane proteins rely on labor-intensive procedures that require highly specialized equipment and reagents. These requirement result in costly and lengthy research and development that limits the full-scale application of these important biomolecules. The proposed technology may provide a way to expedite this research and allow scientists to bring therapies to market more rapidly.This I-Corps project is based on the development of a rapidly assembled, biosensing platform that uses cell-free technologies to integrate transmembrane proteins into a biomimetic sensing device. Transmembrane proteins are a notoriously difficult class of proteins to study but are catalysts of many biological functions in cells and, therefore, also pharmaceutical targets for disease mitigation. The proposed platform takes a specific gene sequence and directly synthesizes transmembrane proteins into a lipid membrane. This proposed process both provides a native-like environment to mimic the cell and circumvents traditionally difficult synthesis. This proposed cell-free synthesis method allows for an open-box reaction that may be engineered and controlled to produce customized proteins rapidly in a wide range of environments. In addition, this makes it ideal to develop sensing platforms that are highly scalable and tunable, such as integration with microfluidic technologies. Currently, this technology has been demonstrated by synthesizing an ion channel into a biomembrane sensor and using this sensor to detect a small-molecule chemical based on electronic changes. The proposed technology uses advancements in biotechnology and bioelectronics and has the potential to provide the next step in membrane protein biosensing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.