Recording membrane potential changes through photoacoustic voltage sensitive dye

Haichong K. Zhang, Jeeun Kang, Ping Yan, Diane Abou, Hanh N.D. Le, Daniel L.J. Thorek, Jin U. Kang, Albert Gjedde, Arman Rahmim, Dean Foster Wong, Leslie M. Loew, Emad Boctor

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


Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

Original languageEnglish (US)
Title of host publicationPhotons Plus Ultrasound: Imaging and Sensing 2017
ISBN (Electronic)9781510605695
Publication statusPublished - 2017
EventPhotons Plus Ultrasound: Imaging and Sensing 2017 - San Francisco, United States
Duration: Jan 29 2017Feb 1 2017


OtherPhotons Plus Ultrasound: Imaging and Sensing 2017
CountryUnited States
CitySan Francisco



  • Fluorescence
  • Membrane potential
  • Photoacoustics
  • Voltage sensitive dye

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

Cite this

Zhang, H. K., Kang, J., Yan, P., Abou, D., Le, H. N. D., Thorek, D. L. J., ... Boctor, E. (2017). Recording membrane potential changes through photoacoustic voltage sensitive dye. In Photons Plus Ultrasound: Imaging and Sensing 2017 (Vol. 10064). [1006407] SPIE.