Customised bifurcating networks for mapping polymer dynamics in shear flows

Understanding the effect of varying shear stresses on individual polymer dynamics is important for applications such as polymer flooding, polymer induced drag reduction, or the design of DNA separation devices. In all cases, the individual polymer response to varying shear flows needs to be understood. A biomimetic design rule was recently proposed for bifurcating networks of rectangular channels of constant depth. These customised microfluidic geometries represent an elegant option to investigate, in a single device, multiple well-controlled shear stresses. Here, we present the first experimental realisation of such customised microfluidic networks, consisting of a series of rectangular microchannels with varying cross-sections, and we demonstrate their potential for testing polymer dynamics. We used microfluidic geometries optimised for both Newtonian and power-law fluids of constant or increasing average wall shear stress. The experimental model systems were tested using particle tracking velocimetry to confirm the theoretically predicted flow fields for shear-thinning xanthan gum solutions and a Newtonian fluid. Then, λ-DNA molecules were used as an example of shear sensitive polymers to test the effect of distinct shear stress distributions on their extension. By observing the conformation of individual molecules in consecutive channels, we demonstrate the effect of the varying imposed stresses. The results obtained are in good agreement with previous studies of λ-DNA extension under shear flow, validating the bifurcating network design. The customised microfluidic networks can thus be used as platforms for the investigation of individual polymer dynamics, in a large range of well-controlled local and cumulative shear stresses, using a single experiment

Optimised multi-stream microfluidic designs for controlled extensional deformation

In this study, we optimise two types of multi-stream configurations (a T-junction and a flow-focusing design) to generate a homogeneous extensional flow within a well-defined region. The former is used to generate a stagnation point flow allowing molecules to accumulate significant strain, which has been found very useful for performing elongational studies. The latter relies on the presence of opposing lateral streams to shape a main stream and generate a strong region of extension in which the shearing effects of fluid–wall interactions are reduced near the region of interest. The optimisations are performed in two (2D) and three dimensions (3D) under creeping flow conditions for Newtonian fluid flow. It is demonstrated that in contrast with the classical-shaped geometries, the optimised designs are able to generate a well-defined region of homogeneous extension. The operational limits of the obtained 3D optimised configurations are investigated in terms of Weissenberg number for both constant viscosity and shear-thinning viscoelastic fluids. Additionally, for the 3D optimised flow-focusing device, the operational limits are investigated in terms of increasing Reynolds number and for a range of velocity ratios between the opposing lateral streams and the main stream. For all obtained 3D optimised multi-stream configurations, we perform the experimental validation considering a Newtonian fluid flow. Our results show good agreement with the numerical study, reproducing the desired kinematics for which the designs are optimised

Stabilization of purely elastic instabilities in cross-slot geometries

In this work, two-phase flows of Newtonian and/or viscoelastic fluids in a 'cross-slot' geometry are investigated both experimentally and numerically in the creeping-flow limit. A series of microfluidic experiments-using Newtonian fluids-have been carried out in different cross-section aspect ratios to support our numerical simulations. The numerical simulations rely on a volume of fluid method and make use of a log-conformation formulation in conjunction with the simplified viscoelastic Phan-Thien and Tanner model. Downstream from the central cross, once the flow has become fully developed, we also estimate analytically the thickness of each fluid layer for both two-and three-dimensional cases. In addition to providing a benchmark test for our numerical solver, these analytical results also provide insight into the role of the viscosity ratio. Injecting two fluids with different elastic properties from each inlet arm is shown to be an effective approach to stabilize the purely elastic instability observed in the cross-slot geometry based on the properties of the fluid with the larger relaxation time. Our results show that interfacial tension can also play an important role in the shape of the interface of the two fluids near the free-stagnation point (i.e. in the central cross). By reducing the interfacial tension force, the interface of the two fluids becomes curved and this can consequently change the curvature of streamlines in this region which, in turn, can modify the purely elastic flow transitions. Thus, increasing interfacial tension is shown to have a stabilizing effect on the associated steady symmetry-breaking purely elastic instability. However, at high values of the viscosity ratio, a new time-dependent purely elastic instability arises most likely due to the change in streamline curvature observed under these conditions. Even when both fluids are Newtonian, outside of the two-dimensional limit, a weak instability arises such that the fluid interface in the depth (neutral) direction no longer remains flat

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease