Meta-optical Miniscope for Multifunctional Imaging

TL;DR

This work introduces a metascope by replacing the miniscope's conventional refractive objective with a single-layer metalens, achieving a dramatically smaller optical path and enabling multifunctional imaging. The authors design and fabricate hyperbolic, square, EDOF, and double-helix metalenses and integrate them with a standard miniscope, demonstrating extended depth of focus, wide-field imaging, and depth sensing within a compact form factor. They provide thorough characterization of PSFs, DOF, FOV, and depth encoding using resolution targets, fluorescent beads, and biological samples, and discuss practical considerations including calibration, aberrations, and system-level optimization. The platform shows promise for versatile, head-mounted imaging with easy plug-and-play customization by swapping the objective lens, with envisioned extensions to edge detection, polarimetry, and hyperspectral capabilities.

Abstract

Miniaturized microscopes (miniscopes) have opened a new frontier in animal behavior studies, enabling real-time imaging of neuron activity while leaving animals largely unconstrained. Canonical designs typically use Gradient-Index (GRIN) lenses or refractive lenses as the objective module for excitation and fluorescence collection, but GRIN lenses suffer from aberrations and refractive lenses are bulky and complex. Meta-optics, composed of subwavelength diffractive elements, offer a promising alternative by combining multiple functionalities with significantly reduced footprint and weight. Here, we present meta-optical miniscopes that integrate functionalities including large field of view (FOV), extended depth of focus (EDOF), and depth sensitivity. These meta-optics replace the traditional refractive lens assembly, reducing the total track length of the objective module from 6.7 mm to 2.5 mm while enhancing imaging performance. Our results demonstrate that meta-optical miniscopes can expand the miniscope toolbox and facilitate the development of more compact and multifunctional imaging systems.

Figures (5)

• Figure 1: Expansion of the miniscope tool-box with smaller optics and multiple functionalities. (a) Schematic illustration of a miniscope, as currently deployed. (b) Comparison of a refractive assembly and a metalens as integrated with the miniscope, showing the difference in total track length (TTL) and working distance (WD) of the objective lens in a traditional miniscope with those of a metalens, highlighting the reduction in system footprint. Inset scale bar corresponds to 1µm. (c) Each metalens serves as the objective lens and is engineered to provide distinct imaging functionalities: the extended depth of focus (EDOF) metalens extends the depth of focus (DOF), the square metalens enables a large field of view (FOV), and the double-helix (DH) metalens supports depth sensing. The animal illustration in (a) is included only to depict the typical placement of a miniscope and does not indicate in-vivo imaging performed in this study.
• Figure 2: Phase profiles and point spread function (PSF) of the refractive lens and meta-optics. (a) The wrapped phase profiles of the central regions of the hyperbolic, square, EDOF, and DH designs. (b) Cross-sectional intensity distributions ($x$–$z$ and $x$–$y$ planes) and relative normalized intensity curves for the refractive, hyperbolic, square, and EDOF designs at different axial depths. (c) PSFs under varying angle of incidence (AOI, 0° to 20°) for the refractive, hyperbolic, square, and EDOF designs. (d) PSF of the DH meta-optic at different depths and the relationship between the rotation angle and depth. Scale bars: (a): 50 µm; (b): 5 µm; (c), (d): 10 µm.
• Figure 3: Performance Characterization of the Metascope (a) Schematic of the resolution imaging setup, consisting of an LED, collimation lens, diffuser, resolution target, and either a miniscope or metascope. For subsequent biological-sample imaging, the internal LED of the miniscope was used instead. (b) Resolution target images acquired with the miniscope and the hyperbolic, square, and EDOF metascopes (left to right) at axial positions of –200 µm, 0 µm, and 200 µm. Insets show intensity profiles across the smallest resolvable features. Blue dashed boxes mark the selected regions when visible. (c) Mouse kidney images acquired at axial positions of -100 µm, 0 µm, and 100 µm. (d) Multilayer fibrous sample images acquired at axial positions of –250 µm, 0 µm, and 250 µm. Scale bars: (b) 50 µm; (c, d) 200 µm.
• Figure 4: Comparison of the imaging performance of different systems for resolving resolution targets and micron-scale fluorescent beads. (a) Measured images of resolution targets acquired using three imaging systems: the miniscope (left), the hyperbolic metascope (center), and the square metascope (right). Representative regions near the periphery are highlighted by red rectangles to compare the aberrations. Scale bars: 50 µm (full-field images); 10 µm (insets). (b) Measured images of 1.9 µm fluorescent beads acquired using the same imaging systems. The overlaid green circles indicate identical FOV across all images for direct comparison. Scale bars, 100 µm. (c) PSF cross-sections corresponding to the circled structures in (b). Each subpanel shows the raw PSF image and its fitted Gaussian intensity profiles along the horizontal and vertical directions. FWHM values are annotated in each subpanel. Scale bars, 5 µm.
• Figure 5: Depth sensing using the DH metascope (a) Schematic diagram illustrating the working principle of depth sensing. Depth information is extracted from the angular differences observed in the measured PSFs. For clarity, the light emitted by the LED is not depicted. (b) Captured images of 1.9 µm fluorescent beads acquired using the miniscope and the DH metascope. The left panel shows the image captured by the miniscope, while the right panels present images acquired by the DH metascope and the corresponding calibration PSFs with similar rotation angles. The red circles highlight representative PSFs used for depth estimation. Scale bars: 50 µm for wide-field images; 20 µm for PSF images.