Lung disease profoundly impacts human health: many lung diseases are currently without cure and require continued treatment. Due to their ease of use and integration into the daily routine, portable inhalers are the preferred treatment option for patients. Efforts to replace greenhouse-gas active portable inhalers have led to portable aqueous systems, so-called Soft mist inhalers (SMIs). However, compared to propellant-driven systems on the market, SMI aerosolization units still face drawbacks in their pathogenic safety, have a big silicon footprint, and must be manufactured in cleanroom environments. Three different types of spray nozzle were developed in this thesis, that improve upon the state of the art in pathogenic safety, fabrication cost, and aerosolization performance. For the first time, a novel 3D-printed, monolithic Swirl nozzle allows the fabrication of such an aerosolization unit outside a cleanroom environment. This device further enables the soft aerosolization of fragile and shear-sensitive large molecule pharmaceutics. A new approach to handling and packaging silicon MEMS allowed the demonstration of the world’s smallest aqueous spray nozzle for portable inhalers with a silicon footprint of just 1/6 of a square millimeter. Improving upon the lacking pathogenic safety of SMI devices, a valved spray nozzle was developed that effectively seals the inhalation unit at nozzle level against pathogenic ingrowth of motile enteric bacteria.

These developments may enable environmentally friendly SMIs to improve the treatment of a broad range of lung diseases.

Lungsjukdom har en enorm påverkan på människors hälsa: många lungsjukdomar saknar för närvarande botemedel och kräver kontinuerlig behandling. På grund av att de är enkla att använda och integrera i den dagliga rutinen är bärbara inhalatorer det föredragna behandlingsalternativet för patienter. Försök att ersätta bärbara inhalatorer som släpper ut växthusgaser har lett till bärbara vattenbaserade system, så kallade soft mist-inhalatorer (SMI). Jämfört med drivmedelsdrivna system på marknaden har enhe- ter för SMI-aerosolisering dock fortfarande nackdelar i sin patogena säkerhet, har ett stort kiselfotavtryck och måste tillverkas i renrumsmiljöer. Tre olika typer av sprutmunstycken utvecklades i denna avhandling, som förbättrar den senaste tekniken vad gäller patogen säkerhet, tillverkningskostnad och aerosoliseringsprestanda. För första gången möjliggör ett nytt 3D-printat, monolitiskt virvelmunstycke tillverkning av en sådan aerosoliseringsenhet utanför en renrumsmiljö. Denna anordning möjliggör mjuk aerosolisering av ömtåliga och skjuvkänsliga läkemedel med stora molekyler. Ett nytt tillvägagångssätt för hantering och för- packning av kisel MEMS möjliggjorde demonstrationen av världens minsta vattenbaserade spraymunstycke för bärbara inhalatorer med ett kiselfotavtryck på bara 1/6 av en kvadratmillimeter. För att förbättra den bristande patogena säkerheten hos SMI-enheter, utvecklades ett ventilförsett spraymunstycke som effektivt tätar inhalationsenheten på munstycksnivå mot patogen inväxt av rörliga enteriska bakterier.

Denna utveckling kan göra det möjligt för miljövänliga SMI:er att förbättra behandlingen av ett brett spektrum av lungsjukdomar.

The geometry of MEMS devices is limited by the technologies used to fabricate them. Today, microsystems are manufactured with patterning technologies that allow only for 2D and 2.5D geometries. These miniaturized devices are widely used in industry, including the automotive, electronics, and biomedical sectors, and their adoption in our society is expected to increaseeven further with the advance of the Internet of Things. 3D MEMS can contribute to this development enabling novel applications and improvedperformances, by exploiting more complex device geometries, and reducing device footprint, by integrating more functionalities onto smaller areas. In recent years, new technologies have been proposed to realize 3D microdevices by directly patterning 3D microstructures and by integrating together microchips manufactured with standard technologies. In this thesis, we develop 3D MEMS devices and fabrication technologies based on both paradigms using femtosecond laser micromachining and the magnetic assembly of tinychips.

The first part of the thesis describes how laser micromachining with ultrashort pulses can be leveraged to achieve both additive and subtractive MEMS manufacturing. Two-photon polymerization of photosensitive resins enables additive manufacturing of 3D microstructures with sub-micron resolution. However, the kinds of devices, geometries, and materials that can be currently printed by two-photon polymerization are still limited, thus we set out to address some of these limitations. In the first work, we fabricate functional 3D printed accelerometers combining self-shadow masking features with directional metallization. In the second work, we demonstrate the realization of long overhanging structures (∼ 1mm) using the consecutive printing of short sections. In the third work, we 3D print polyimide, a high-performing polymer that can be used in harsh environments, where typical 3D printedpolymers are not suitable. Subtractive manufacturing by laser micromachining is demonstrated in the fourth work, where through-silicon-holes with high quality are formed using water-assisted drilling in a simple fabrication setup ,where the laser is focused on the front side of a silicon substrate and water is in contact with the backside.

The second part of the thesis describes the integration of fragile and tiny MEMS devices coated with ferromagnetic thin films into silicon and polymeric substrates. The micromachined magnetized chips are integrated into receiving structures using permanent magnets. Magnetic interactions allow the non-contact handling and the vertical placement of chips at a scale and speed that is challenging for industry standard pick-&-place tools. In the fifth work, thin silicon chips for electrochemical sensing are magnetically assembled in vertical position and laterally wire bonded. In the sixth work, silicon micromachined spray nozzle chips with a diameter below 300 μm are magnetically assembled and sealed on acrylic sheets, to be used in portable soft mist inhalers.