Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor

Meng Zhang, Jessie Peh, Paul J. Hergenrother, Brian T. Cunningham

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

High throughput screening of protein-small molecule binding interactions using label-free optical biosensors is challenging, as the detected signals are often similar in magnitude to experimental noise. Here, we describe a novel self-referencing external cavity laser (ECL) biosensor approach that achieves high resolution and high sensitivity, while eliminating thermal noise with sub-picometer wavelength accuracy. Using the self-referencing ECL biosensor, we demonstrate detection of binding between small molecules and a variety of immobilized protein targets with binding affinities or inhibition constants in the sub-nanomolar to low micromolar range. The demonstrated ability to perform detection in the presence of several interfering compounds opens the potential for increasing the throughput of the approach. As an example application, we performed a 'needle-in-the-haystack' screen for inhibitors against carbonic anhydrase isozyme II (CA II), in which known inhibitors are clearly differentiated from inactive molecules within a compound library.

Original languageEnglish (US)
Title of host publication2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages2073-2076
Number of pages4
ISBN (Electronic)9781424479290
DOIs
StatePublished - Nov 2 2014
Event2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014 - Chicago, United States
Duration: Aug 26 2014Aug 30 2014

Publication series

Name2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014

Other

Other2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014
CountryUnited States
CityChicago
Period8/26/148/30/14

Fingerprint

Laser resonators
Biosensing Techniques
Biosensors
Lasers
Proteins
Molecules
Throughput
Carbonic anhydrase
Immobilized Proteins
Carbonic Anhydrase II
Thermal noise
Needles
Isoenzymes
Libraries
Noise
Labels
Screening
Hot Temperature
Wavelength

ASJC Scopus subject areas

  • Health Informatics
  • Computer Science Applications
  • Biomedical Engineering

Cite this

Zhang, M., Peh, J., Hergenrother, P. J., & Cunningham, B. T. (2014). Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor. In 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014 (pp. 2073-2076). [6944024] (2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014). Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/EMBC.2014.6944024

Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor. / Zhang, Meng; Peh, Jessie; Hergenrother, Paul J.; Cunningham, Brian T.

2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014. Institute of Electrical and Electronics Engineers Inc., 2014. p. 2073-2076 6944024 (2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Zhang, M, Peh, J, Hergenrother, PJ & Cunningham, BT 2014, Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor. in 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014., 6944024, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014, Institute of Electrical and Electronics Engineers Inc., pp. 2073-2076, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014, Chicago, United States, 8/26/14. https://doi.org/10.1109/EMBC.2014.6944024
Zhang M, Peh J, Hergenrother PJ, Cunningham BT. Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor. In 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014. Institute of Electrical and Electronics Engineers Inc. 2014. p. 2073-2076. 6944024. (2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014). https://doi.org/10.1109/EMBC.2014.6944024
Zhang, Meng ; Peh, Jessie ; Hergenrother, Paul J. ; Cunningham, Brian T. / Detection of protein-small molecule binding using a self-referencing external cavity laser biosensor. 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014. Institute of Electrical and Electronics Engineers Inc., 2014. pp. 2073-2076 (2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014).
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