Recording membrane potential changes through photoacoustic voltage sensitive dye

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

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

2 Scopus citations


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
Title of host publicationPhotons Plus Ultrasound
Subtitle of host publicationImaging and Sensing 2017
EditorsAlexander A. Oraevsky, Lihong V. Wang
ISBN (Electronic)9781510605695
StatePublished - 2017
EventPhotons Plus Ultrasound: Imaging and Sensing 2017 - San Francisco, United States
Duration: Jan 29 2017Feb 1 2017

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
ISSN (Print)1605-7422


ConferencePhotons Plus Ultrasound: Imaging and Sensing 2017
Country/TerritoryUnited States
CitySan Francisco


  • Fluorescence
  • Membrane potential
  • Photoacoustics
  • Voltage sensitive dye


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