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Exploiting Kinetics for Unparalleled Fidelity in Molecular Systems

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Thursday, December 14, 2023, 10 am

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Chemical Engineering Seminar

Dr. Alexander Johnson-Buck

Chief Scientific Officer
aLight Sciences, Inc.


In contrast to the deterministic behavior typical of bulk chemical systems, single molecules exhibit highly stochastic dynamics that are well-defined only in a statistical sense. Despite this randomness, nature has devised systems that perform DNA replication, polypeptide synthesis, and other critical tasks with extremely high fidelity and temporal coordination at the single-molecule level. To date, however, synthetic molecular systems have not attained this degree of fidelity, limiting the performance of engineered nanomaterials in domains such as molecular diagnostics and imaging. In this talk, I will discuss our work to introduce greater determinism into both the sensing and dynamic behaviors of single biomolecules. In one example, we have developed an approach called single-molecule kinetic fingerprinting that achieves amplification-free detection of cancer mutations with a specificity greater than droplet digital PCR. This approach has also been adapted to the ultrasensitive quantification of protein biomarkers in serum and other biofluids. In a second example, we have engineered single-molecule clocks to exhibit well-defined (i.e., narrowly distributed) time delays between signaling events, paving the way for more precise temporal coordination in molecular systems. In closing, I will discuss plans to extend this work to more sophisticated systems such as artificial kinetic proofreaders or molecular sensors with internal memory, with planned applications such as low-cost, high-performance medical diagnostics and massively multiplexed spatial multi-omic imaging.


Alex Johnson-Buck completed his PhD at the University of Michigan in the laboratory of Nils Walter, where he designed and characterized DNA nanostructures and molecular robots. As a postdoctoral fellow at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School, he worked with William Shih to design and build the first quasi-deterministic single-molecule clocks. He subsequently co-invented and spearheaded the development of a digital single-molecule sensing technology based on kinetic fingerprinting, and has pursued its commercialization as Chief Scientific Officer of the startup company aLight Sciences. Alex has received several awards and honors, including Outstanding Male Graduating Senior (Northern Michigan University), the Kasimir Fajans Award for Best Dissertation (University of Michigan), and the Rackham Outstanding Graduate Student Instructor Award (University of Michigan). He envisions a future where the stochastic dynamics of single molecules can be tamed to build useful molecular devices whose performance exceeds that of any natural system. As an avid skier, he actually enjoys frigid winters that bring hundreds of inches of lake effect snow.

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