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In microfluidics, a well-known challenge is to obtain reproducible results, often constrained by unstable pressures or flow rates. Today, there are existing stabilisers made for low-pressure microfluidics or high-pressure macrofluidics, often consisting of passive membranes, which cannot stabilise long-term fluctuations. In this work, a novel stabilisation method that is able to handle high pressures in microfluidics is presented. It is based on upstream flow capacitance and thermal control of the fluid's viscosity through a PID controlled restrictor-chip. The stabiliser consists of a high-pressure-resistant microfluidic glass chip with integrated thin films, used for resistive heating. Thereby, the stabiliser has no moving parts. The quality of the stabilisation was evaluated with an ISCO pump, an HPLC pump, and a Harvard pump. The stability was greatly improved for all three pumps, with the ISCO reaching the highest relative precision of 0.035% and the best accuracy of 8.0 ppm. Poor accuracy of a pump was compensated for in the control algorithm, as it otherwise reduced the capacity to stabilise longer times. As the dead volume of the stabiliser was only 16 nL, it can be integrated into micro-total-analysis- or other lab-on-a-chip-systems. By this work, a new approach to improve the control of microfluidic systems has been achieved. De två första författarna delar förstaförfattarskapet.

Microfluidics exploiting the phenomenon of inertial focusing have attracted much attention in the last decade as they provide the means to facilitate the detection and analysis of rare particles of interest in complex fluids such as blood and natural water. Although many interesting applications have been demonstrated, the systems remain difficult to engineer. A recently presented line of the technology, inertial focusing in High Aspect Ratio Curved microfluidics, has the potential to change this and make the benefits of inertial focusing more accessible to the community. In this paper, with experimental evidence and fluid simulations, we provide the two necessary equations to design the systems and successfully focus the targets in a single, stable, and high-quality position. The experiments also revealed an interesting scaling law of the lift force, which we believe provides a valuable insight into the phenomenon of inertial focusing.

The ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks, and specially a recently presented variant, inertial focusing in High Aspect Ratio Curved systems (HARC sytsems), where the systems are easily engineered and focus the targets together in a stable position over a wide range of particle sizes and flow rates. However, although convenient for laser interrogation and concentration, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm. In addition to the concept for particle separation, a model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 µm in diameter) in silicon-glass microchannels, where the resolution in the separation could be modulated by the radius of the channel. With the capacity to focus sub-micron particles and to separate them with high resolution, we believe that inertial focusing in HARC systems is a technology with the potential to facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.

The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures. These authors contributed equally: Anna Fornell and Hannah Pohlit

The pressure drop across a stenotic vessel is an important parameter in medicine, providing a commonly used and intuitive metric for evaluating the severity of the stenosis. However, non-invasive estimation of the pressure drop under pathological conditions has remained difficult. This study demonstrates a novel method to quantify the irreversible pressure drop across a stenosis using 4D Flow MRI by calculating the total turbulence production of the flow. Simulation MRI acquisitions showed that the energy lost to turbulence production can be accurately quantified with 4D Flow MRI within a range of practical spatial resolutions (1-3 mm; regression slope = 0.91, R-2 = 0.96). The quantification of the turbulence production was not substantially influenced by the signal-to-noise ratio (SNR), resulting in less than 2% mean bias at SNR amp;gt; 10. Pressure drop estimation based on turbulence production robustly predicted the irreversible pressure drop, regardless of the stenosis severity and post-stenosis dilatation (regression slope = 0.956, R-2 = 0.96). In vitro validation of the technique in a 75% stenosis channel confirmed that pressure drop prediction based on the turbulence production agreed with the measured pressure drop (regression slope = 1.15, R-2 = 0.999, Bland-Altman agreement = 0.75 +/- 3.93 mmHg). Funding Agencies|European Research Council [310612]; Swedish Research Council [2013-6077, 2014-6191]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2016R1A6A3A03006337]