Axially multifocal metalens for 3D volumetric photoacoustic imaging of neuromelanin in live brain organoid

Optical resolution photoacoustic imaging of uneven samples without z-scanning is transformative for the fast analysis and diagnosis of diseases. However, current approaches to elongate the depth of field (DOF) typically imply cumbersome postprocessing procedures, bulky optical element ensembles, or substantial excitation beam side lobes. Metasurface technology allows for the phase modulation of light and the miniaturization of imaging systems to wavelength-size thickness. Here, we propose a metalens composed of submicrometer-thick titanium oxide nanopillars, which generates an elongated beam of diffraction-limited diameter with an aspect ratio of 286 and a uniform intensity throughout the DOF. The metalens enhances visualization of phantom samples with tilted surfaces compared to conventional lenses. Moreover, the volumetric imaging of neuromelanin is facilitated for depths of up to 500 micrometers within the human midbrain and forebrain organoids that are 3D biological models of human brain regions. This approach provides a miniaturized platform for neurodegenerative disease diagnosis and drug discovery.