Prior to joining the University of California at Santa Barbara in 1998 Dr. Plaxco received his Ph.D. from Caltech and performed postdoctoral studies at Oxford and the University of Washington. Dr. Plaxco has co-authored more than 180 papers on protein folding, protein dynamics, folding-based biosensors and folding-based smart materials. He has also co-authored a popular science book on Astrobiology and more than a dozen patents. He is actively involved in the commercialization of the novel technologies emerging from his laboratory and serves on the scientific advisory boards of a half dozen companies.
Research Group Website: https://plaxco.chem.ucsb.edu/
Biomolecular recognition is versatile, specific and high affinity, observations that have motivated decades of research aimed at adapting biomolecules into a general platform for molecular sensing. Despite significant effort, however, these so-called “biosensors” have almost entirely failed to achieve their potential as reagentless, real-time analytical devices; the only quantitative, reagentless biosensor to achieve commercial success to date is the glucose sensor employed by millions of diabetics. The fundamental stumbling block that has precluded more widespread success in the biosensor field is the failure of most biomolecules to produce any easily measured signal upon target binding –that is, biomolecules typically do not change their shape or dynamics, or emit light or electrons when they bind their recognition partners. Because of this, it has proven difficult to transduce biomolecular binding events into a measurable output signal that is not readily spoofed by the binding of any of the many interferrents present in realistically complex samples. In recent years, however, we have developed a potential solution to this problem based on the binding-induced “folding” of protein and nucleic acid-based receptors. These folding-based sensors are rapid (responding in seconds to minutes), sensitive (detecting sub-picomolar to micromolar), reagentless, and have already been generalized to a wide range of specific protein, nucleic acid and small molecule targets. Moreover, because their signaling is linked to a binding-specific change in the physics of the probe biomolecule –and not simply to adsorption of the target onto the sensor head- this platform is selective enough to be employed directly in blood, soil, cell lysates and other grossly contaminated clinical and environmental samples. Indeed, we have recently demonstrated their ability to quantitatively monitor a specific small molecule in real-time directly in the blood of living, anesthetized animals. Because of their sensitivity, substantial background suppression and operational convenience, these folding-based biosensors appear potentially well suited for electronic, on-chip applications in pathogen detection, proteomics, metabolomics and drug discovery.
Recent Research Publications
- Vinh, N.Q., Sherwin, M.S., Allen, S.J., George, D.K., Rahmani, A.J. and Plaxco, K.W. (2015) “Insights into the femtosecond-to-picosecond dynamics of liquid water from ultra-high-precision gigahertz-to-terahertz spectroscopy of aqueous salt solutions.” J. Chem. Phys., 142, 164502
- Hsieh, K., Ferguson, B., Eisenstein, M., Plaxco, K.W. and Soh, H. (2015) “Integrated electrochemical microsystems for genetic detection of pathogens at the point of care.” Acc. Chem. Res., 48, 911-920
- Adornetto, G., Porchetta, A., Palleschi, G., Plaxco, K.W. and Ricci, F. (2015) “A general approach to the design of allosteric, transcription-factor-regulated DNAzymes.” Chem. Sci., 6, 3692-3696
- Watkins, H. Simon, A.J., Sosnick, T.R., Lipman, E.A., Hjelm, and Plaxco, K.W. (2015) “A random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions.” Proc. Natl. Acad. Sci. USA, 112, 6631-6636
- Ranallo, S., Vallée-Bélisle, A., Plaxco, K.W. and Ricci, F. (2015) “A modular, DNA-based ‘beacon’ for the single-step fluorescence measurement of antibodies and other proteins.” Angewandte, 54, 13214–13218
- Mao, X., Simon, A.J., Shi, J., Li, J., Huang, Q., Plaxco, K.W. and Fan, C. (2016) “Activity modulation and allosteric control of a scaffolded DNAzyme using a dynamic DNA nanostructure.” Chem. Sci., 7, 1200-1204
- Ricci, F., Vallée-Bélisle, A., Simon, A.J., Porchetta, A. and Plaxco, K.W. (2016) “Using Nature’s ‘tricks’ to rationally tune the binding properties of biomolecular receptors.” Acc. Chem. Res., 49, 1884-1892
- Kang, D., Ricci, F., White, R.J. and Plaxco, K.W. (2016) “A survey of redox-active moieties for application in multiplexed electrochemical biosensors.” Anal. Chem., 88, 10452-10458
- Daupin-Ducharme, P. and Plaxco, K. W. (2016) “Maximizing the signal gain of electrochemical-DNA sensors.” Anal. Chem., 88, 11654-11662
- Li, H., Arroyo-Currás, N., Kang, D., Ricci, F. and Plaxco, K.W. (2016) “Dual-reporter drift correction to enhance the performance of electrochemical aptamer-based sensors in whole blood.” J. Am. Chem. Soc., 138, 15809-1581
- Arroyo-Currás, N., Somerson, J., Vieira, P., Ploense, K., Kippin, T. and Plaxco, K.W. (2017) “Real-time measurement of small molecules in awake, ambulatory animals.” Proc. Natl. Acad. Sci. USA, 114, 645–650
- Simon, A.J., Walls-Smith, L.T., Freddi, M., Fong, F.Y., Gubala, V. and Plaxco, K.W. (2017) “Quantitative measurement of the molecular- and micron-scale dissolution kinetics of responsive DNA hydrogels.” ACS Nano, 1, 461–468
- Hauke, A., Selva Kumar, L.S., Kim, M.Y., Pegan, J., Khine, M., Li, H., Plaxco, K.W. and Heikenfeld, J. (2016) “Superwetting and aptamer functionalized shrink-induced high surface area electrochemical sensors.” Biosens. Bioelec., 94, 438-442
- Li, H., Dauphin-Ducharme, P., Arroyo-Currás, N., Tran, C., Vieira, P.A., Li, S., Shin, C., Somerson, J., Kippin, T.E. and Plaxco, K.W. (2017) “A biomimetic, phosphatidylcholine-terminated monolayer greatly improves the in-vivo performance of electrochemical aptamer-based sensors.” Angewandte, In press.
- Mariottini, D., Idili, A., Vallee-Belisle, A., Plaxco, K.W. and Ricci, F. (2017) “A DNA nanodevice that loads and releases a cargo with hemoglobin-like allosteric control and cooperativity.” Nano. Lett., In press.
- Dauphin-Ducharme, P., Arroyo-Currás, N., Kurnik, M., Ortega, G., Li, H., and Plaxco, K.W. (2017) “A simulation-based approach to determining electron transfer rates using square-wave voltammetry.” Langmuir, In press.