Development of a mesh nebulizer for high-yield generation of 1–5  <i>μ</i> m aerosols

Liquid atomization is a key factor in inhalation therapy because it determines where inhaled aerosols deposit within the respiratory tract. Delivery to the deep lung generally requires aerosol generation in the range of 1–5 μm. However, current medical nebulizers often struggle to produce aerosols in this size range at high yield and tend to generate an undesirable coarse aerosol fraction. In mesh nebulizers, which are compact, quiet, and increasingly used in clinical settings, the nozzle-aperture diameter governs the resulting aerosol size. In this study, we fabricated nozzle-array filters with submicrometer-to-few-micrometer apertures—which are difficult to realize via conventional methods—using multistep exposure x-ray lithography, and demonstrated high-yield generation of 1–5 μm aerosols with a mesh nebulizer. We fabricated filters with mean aperture diameters of 7.5, 2.3, and 1.6 μm at NewSUBARU BL11 and evaluated them using a commercial piezoelectric oscillator unit. Laser diffraction measurements showed that the median aerosol diameter decreased systematically with aperture diameter, from 12.5 to 4.8 and 3.2 μm, with the smallest-aperture filter producing aerosols predominantly within the target 1–5 μm range for inhalation therapy. We also examined the dependence of nebulization performance on liquid properties and confirmed stable aerosol generation within the 1–5 μm range for a clinically relevant aqueous formulation. These results establish a practical route to 1–5 μm aerosol generation through aperture-controlled nozzle-array design and x-ray lithography-based fabrication.