chips during packaging steps. From a pure MEMS functionality perspective, this makes the chips unnecessarily large and expensive.An example of MEMS devices that suffer from these shortcomings are silicon spray nozzles for portable inhalers. Portable inhalers are the primary treatment option for common lung diseases such as chronic obstructive pulmonary disease (COPD), [2] cystic fibrosis, [3] and asthma. [4] Currently the market for portable inhalers is dominated by two types of portable inhalers: dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs). [5] DPIs aerosolize a dry powder formulation using the inspiratory effort of the user to disperse the powder in the airstream. This passive aerosolization, however, limits their applicability to elderly patients and children. [2] Further, not all pharmaceutics can be formulated for DPIs due to the required drying step of the pharmaceutics. [6] pMDIs feature active aerosol generation, enabled by the use of propellants: liquids with a high vapor pressure that pressurize the drug formulation inside of the cartridge. [7] Increasingly this class of inhalation devices faces regulatory restrictions due to the global warming potential of the used propellants. [2,8] Currently, pMDIs account for roughly 54% of all portable inhalers sold worldwide [2] and continue to be the most affordable treatment option for many aerosolized pharmaceutics. [2] A typical Salbutamol pMDI inhaler can be available from as low as US $0.83 in India to 2€ in most of Europe and up to US $48 in the US. [2] Soft mist inhalers (SMIs) are a third, developing category of portable inhalers. They have been conceived to allow the aerosolization of a soft aqueous mist that improves both drug delivery characteristics and environmental impact compared to current propellant-based devices. [9,10] SMIs can aerosolize an aqueous drug solution for example using a spring system. [10] They thereby avoid the use of propellants while still allowing for an active aerosol generation, making SMIs suitable for a wide range of patients. Further, aqueous solutions are used in non-portable, desktop-size inhalers such as jet nebulizers, where for example new treatment options for cystic fibrosis (CF) by gene-editing are explored. [6] A transfer of such pharmaceuticals to a portable device could be straightforward for SMIs. The Boehringer Ingelheim system is the only SMI device listed in ref. [5] for comparison, and is sold between US $ 332The functional area of silicon-based microelectromechanical systems (MEMS) devices often occupies only a fraction of the actual silicon area of the chip. As the chip cost directly scales with the total chip area, there is an incentive to reduce the chip to the smallest possible size. However, handling such diminutive devices poses challenges that industry-standard packaging cannot solve. Here, the world's smallest spray nozzle chip for drug delivery to the lung is manufactured and packaged and how magnetic assembly combined with microfluidic glue fixation can overcome this ...
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