We present microfluidic chip based devices that produce liquid jets with micrometer diameters while operating at very low flow rates. The chip production is based on established soft-lithographical techniques employing a three-layer design protocol. This allows the exact, controlled and reproducible design of critical parts such as nozzles and the production of nozzle arrays. The microfluidic chips reproducibly generate liquid jets exiting at perfect right angles with diameters between 20 μm and 2 μm, and under special circumstances, even down to 0.9 μm. Jet diameter, jet length, and the domain of the jetting/dripping instability can be predicted and controlled based on the theory for liquid jets in the plate-orifice configuration described by Gañán-Calvo et al. Additionally, conditions under which the device produces highly reproducible monodisperse droplets at exact and predictable rates can be achieved. The devices operate under atmospheric and under vacuum conditions making them highly relevant for a wide range of applications, for example, for free-electron lasers. Further, the straightforward integration of additional features such as a jet-in-jet is demonstrated. This device design has the potential to integrate more features based on established microfluidic components and may become a standard device for small liquid jet production.
In biological fluids, proteins bind to particles, forming so-called protein coronas. Such adsorbed protein layers significantly influence the biological interactions of particles, both in vitro and in vivo. The adsorbed protein layer is generally described as a two-component system comprising "hard" and "soft" protein coronas. However, a comprehensive picture regarding protein corona structure is lacking. Herein, we introduce an experimental approach that allows for in situ monitoring of protein adsorption onto silica microparticles. The technique, which mimics flow in vascularized tumors, combines confocal laser scanning microscopy with microfluidics and allows the study of the time-evolution of protein corona formation. Our results show that protein corona formation is kinetically divided into three different phases: phase 1, proteins irreversibly and directly bound (under physiologically relevant conditions) to the particle surface; phase 2, irreversibly bound proteins interacting with pre-adsorbed proteins, and phase 3, reversibly bound "soft" protein corona proteins. Additionally, we investigate particle-protein interactions on lowfouling zwitterionic-coated particles where the adsorption of irreversibly bound proteins does not occur, and on such particles only a "soft" protein corona is formed. The reported approach offers the potential to define new state-of-the art procedures for kinetics and protein fouling experiments. 9 Depending on the characterization method used, the protein corona is described according to either the Gibbs free energy ΔG, 8,10-12 which defines the adsorption and desorption rates of proteins, or binding force 13,14 between the proteins and particle surface. Proteins with a large ΔG have a low probability of desorption and therefore remain associated with the particle surface. These proteins are considered to form the "hard" protein corona. Distinction based on binding forces implies that "hard" protein corona proteins interact directly with the particle surface through long-range, strong protein-surface interactions, whereas proteins in the "soft" protein corona interact with other proteins through short-range, weak protein-protein interactions. Another theoretical distinction is based on the persistence of the protein to remain adsorbed throughout the nanoparticle's journey (i.e. from bloodstream to tissue and past-endocytic environments) as protein corona composition changes during biophysical events. 6-8,15,16 The concept of "persistent" proteins 5 originates from studies where the "hard" protein corona is used to follow the particle's past. 17-19 It is becoming increasingly important to clearly understand the complex process of protein corona formation, with a focus on the influence of the "soft" protein corona on physiological interactions. 4,7,13,20-24 However, to do so, it is crucial to acquire and understand further details such as the time-evolution of protein corona formation. Existing techniques for investigating the protein corona can be divided into ex situ and in situ ...
We present a microfluidic nozzle device for the controlled continuous solution blow spinning of ultrafine fibers. The device is fabricated by soft lithography techniques and is based on the principle of a gas dynamic virtual nozzle for precise three-dimensional gas focusing of the spinning solution. Uniform fibers with virtually endless length can be produced in a continuous process while having accurate control over the fiber diameter. The nozzle device is used to produce ultrafine fibers of perfluorinated copolymers and of polycaprolactone, which are collected and drawn on a rotating cylinder. Hydrodynamics and mass balance quantitatively predict the fiber diameter, which is only a function of flow rate and air pressure, with a small correction accounting for viscous dissipation during jet formation, which slightly reduces the jet velocity. Because of the simplicity of the setup, the precise control of the fiber diameter, the positional stability of the exiting ultrafine fiber and the potential to implement arrays of parallel channels for high throughput, this methodology offers significant benefits compared to existing solution-based fiber production methods.
The manufacturing of inserts for micro injection moulding made of mortar material is presented in this work. The fabrication of the mortar insert described in this publication relied on a versatile and relatively fast rapid prototyping process based on soft tooling. The mortar insert has a QR code with micro features on its surface, which was replicated in acrylonitrile butadiene styrene (ABS) polymer by the micro injection moulding process. With this approach, it is possible to fabricate hard inserts for micro injection moulding purposes that are able to compete with conventional-made inserts made of tool steel.
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