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. 2025;1(1):5.
doi: 10.1038/s44384-025-00008-7. Epub 2025 Apr 24.

Achieving single cell acoustic localisation with deactivation super resolution

Cameron A B Smith  1   2 , Mengtong Duan  2 , Jipeng Yan  1 , Laura Taylor  1 , Mikhail Shapiro  2   3   4 , Meng-Xing Tang  1
Affiliations

Achieving single cell acoustic localisation with deactivation super resolution

Cameron A B Smith et al. NPJ Acoust. 2025.

Abstract

Photo-activated localization microscopy (PALM) has been a game-changer, breaking the diffraction limit in spatial resolution. This study presents the Deactivation Super Resolution (DSR) method, which utilises the deactivation of genetically encodable contrast agents, enabling us to super-resolve and pinpoint individual cells with ultrasound as they navigate through structures which cannot be resolved by conventional B-Mode imaging. DSR takes advantage of Gas Vesicles (GVs), which are air-filled sub-micron particles that have been expressed in genetically engineered bacterial and mammalian cells to produce acoustic contrast. Our experimental results show that DSR can distinguish sub-wavelength microstructures that standard B-mode ultrasound images fail to resolve by super-localising individual mammalian cells. This study provides a proof of concept for the potential of DSR to serve as a super-resolution ultrasound technique for individual cell localisation, opening new horizons in the field.

Keywords: Biological techniques; Engineering; Health care.

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Conflict of interest statement

Competing interestsThe authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic demonstrating the pulse-echo structure and the processing involved in generating deactivation images.
Fig. 2
Fig. 2
Schematic diagram showing the processing pipeline for deactivation super-resolution.
Fig. 3
Fig. 3
schematic diagram (top) showing the genetically engineered MDA cells (adapted from ref. ) flowing through the tube in set positions, and below representative sample deactivation image frames.
Fig. 4
Fig. 4
Representative deactivation super resolution image (top) and two cut through line plots showing the separation of the tubes at two positions, bar charts showing the mean and standard error of FWHM (n = 6) and tube separation distances (n = 3).
Fig. 5
Fig. 5
Concentration sweeps demonstrating the number of cell localisations with deactivation super-resolution imaging compared to the expected number of cells based on the cell concentration flowing at 3 levels of buoyancy purification, along with a summary figure (bottom right) showing the percentage of localised cells across the different concentrations for each purification method.
Fig. 6
Fig. 6
Flow cytometry showing GFP and BFP expression across induced, non-induced, and purified cells.
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