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.

Single-molecule fluorescence spectroscopy offers unique capabilities for the low-concentration sensing and probing of molecular dynmics. However, employing such a methodology for versatile sensing and diagnostics under point-of-care demands device miniaturization to lab-on-a-chip size. In this study, we numerically design metalenses with high numerical aperture (NA = 1.1), which are composed of silicon nitride nanostructures deposited on a waveguide and can selectively focus guided light into an aqueous solution at two wavelengths of interest in the spectral range of 500–780 nm. Despite the severe chromatic focal shift in the lateral directions owing to the wavelength-dependent propagation constant in a waveguide, segmented on-chip metalenses provide perfectly overlapping focal volumes that meet the requirements for epi-fluorescence light collection. We demonstrate that the molecule detection efficiencies of metalenses designed for the excitation and emission wavelengths of ATTO 490LS, Alexa 555, and APC-Cy7 tandem fluorophores are sufficient to collect several thousand photons per second per molecule at modest excitation rate constants. Such sensitivity provides reliable diffusion fluorescence correlation spectroscopy analysis of single molecules on a chip to extract their concentration and diffusion properties in the nanomolar range. Achromatic on-chip metalenses open new avenues for developing ultra-compact and sensitive devices for precision medicine and environmental monitoring.

Waveguide-integrated metasurfaces offer a promising platform for ultracompact on-chip optical systems, enabling applications such as fluorescence sensing, holography, and near-eye displays. In particular, integrated achromatic metalenses that couple guided modes to free-space radiation are highly desirable for single-molecule fluorescence sensing, where high numerical aperture (NA), efficient light focusing, and consistent focal volume overlap across excitation and emission wavelengths are critical. However, designing integrated high-NA metalenses with multi-wavelength operation remains fundamentally challenging due to the wavelength-dependent propagation of guided modes. Here, we present an inverse design framework that simultaneously optimizes the geometries and positions of silicon nitride nanofins atop a slab waveguide to achieve diffraction-limited focusing at three wavelengths with unity NA. The resulting metalens outperforms conventional segmented designs in focusing efficiency and sidelobe suppression, particularly at wavelengths corresponding to the excitation and emission bands of the model fluorophore Alexa Fluor 647. Numerical analysis shows that the design yields a high molecule detection efficiency suitable for epi-fluorescence single-molecule sensing. This work highlights the potential of inverse-designed metalenses as a versatile on-chip platform for advanced applications in fluorescence spectroscopy, augmented reality, or optical trapping.

Mie voids have been recently demonstrated as a promising nanophotonic platform for light manipulation and optical sensing. Moreover, the detection volumes of Mie void cavities exceed those of optical nanoantennas, making them appropriate for low-concentration single-molecule fluorescence biosensing. However, the fluorescence enhancement quantification of diffusing molecules in such optical antenna systems has not been addressed. Here, we explore Mie void ability to enhance the single-molecule fluorescence of diffusing fluorophores AF647 with the help of fluorescence correlation spectroscopy. The optimized structure confines 635 nm laser light within a well-defined excitation volume in the Mie void and provides the excitation intensity enhancement. We monitor the reduction in the number of molecules, signifying the detection volume reduction in the Mie void and an increase in single-molecule brightness up to 2.8 times. However, we reveal that the observed fluorescence enhancement appears limited owing to the azimuthally symmetric emission direction away from the optical axis when the molecules diffuse in the vicinity of the Mie void entrance. Altogether, this study demonstrates exploration of Mie void-based nanoantenna potential for single-molecule fluorescence spectroscopy applications.

Single molecule fluorescence spectroscopy offers unique capabilities of low concentration sensing or probing molecular dynamics. However, employment of such methodology for versatile sensing and diagnostics under point-of-care demands device miniaturization down to lab-on-a-chip sizes. Here, we numerically design metalenses with high NA of 1.1 that are composed of silicon nitride nanostructures deposited on a waveguide and may selectively focus guided light into an aqueous solution at two wavelengths of interest in a spectral range between 500 and 780 nm. Despite the chromatic focal shift in lateral directions owing to the wavelength-dependent propagation constant in a waveguide, a segmented metalens provides perfectly overlapped focal volumes which meets the requirements for epi-fluorescence light collection. We demonstrate that the molecule detection efficiencies for metalenses designed for excitation and emission wavelengths of fluorophores ATTO 490LS, Alexa 555, APC-Cy7 tandem are sufficient to collect several thousand of photons per second per molecule at modest excitation rate constants. Such sensitivity provides a reliable diffusion fluorescence correlation spectroscopy analysis of single molecules on chip to ex-tract their concentration and diffusion properties in the nanomolar range. Altogether, an achromatic integrated metalens opens new avenues for development of ultracompact and sensitive devices for precision medicine and environmental monitoring.