Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution

In vitro prediction of physiologically relevant transport of therapeutic molecules across the microcirculation represents an intriguing opportunity to predict efficacy in human populations. On-chip microvascular networks (MVNs) show physiologically relevant values of molecular permeability, yet like most systems, they lack an important contribution to transport: the ever-present fluid convection through the endothelium. Quantification of transport through the MVNs by current methods also requires confocal imaging and advanced analytical techniques, which can be a bottleneck in industry and academic laboratories. Here, it is shown that by recapitulating physiological transmural flow across the MVNs, the concentration of small and large molecule therapeutics can be directly sampled in the interstitial fluid and analyzed using standard analytical techniques. The magnitudes of transport measured in MVNs reveal trends with molecular size and type (protein versus nonprotein) that are expected in vivo, supporting the use of the MVNs platform as an in vitro tool to predict distribution of therapeutics in vivo

Exploring voltage mediated delamination of suspended 2D materials as a cause of commonly observed breakdown

Two-dimensional (2D) barrier materials such as graphene, boron nitride, and molybdenum disulfide hold great promise for important applications such as DNA sequencing, desalination, and biomolecular sensing. The 2D materials commonly span pores through an insulating membrane, and electrical fields are applied to drive cross-barrier transport of charged solvated species. While the low-voltage transmembrane transport is well-understood and controllable, high-voltage phenomena are uncontrolled and result in the apparent breakdown of the 2D material's critical insulating properties. Here we use suspended graphene over a 50 nm silicon nitride nanopore as a model system and show that delamination of the 2D material occurs at higher voltages and can directly cause a number of the puzzling high-voltage transport observations. We confirm the occurrence of delamination and observe via atomic force microscopy measurement a micron-scale delaminated patch in a system using chemical vapor deposition graphene. Furthermore, we show that the conductivity of the same system is strongly correlated to the area of delamination via coincident current measurements and optical imaging of the delaminated area. Finally, we demonstrate that delamination alone can cause a dramatic breakdown of barrier function through observation of a reversible increase in conductance of samples prepared with pristine defect-free graphene. These findings should have a great impact on the design and interpretation of 2D barrier material for both experiments and applications

Exploring voltage mediated delamination of suspended 2D materials as a cause of commonly observed breakdown

\u3cp\u3eTwo-dimensional (2D) barrier materials such as graphene, boron nitride, and molybdenum disulfide hold great promise for important applications such as DNA sequencing, desalination, and biomolecular sensing. The 2D materials commonly span pores through an insulating membrane, and electrical fields are applied to drive cross-barrier transport of charged solvated species. While the low-voltage transmembrane transport is well-understood and controllable, high-voltage phenomena are uncontrolled and result in the apparent breakdown of the 2D material's critical insulating properties. Here we use suspended graphene over a 50 nm silicon nitride nanopore as a model system and show that delamination of the 2D material occurs at higher voltages and can directly cause a number of the puzzling high-voltage transport observations. We confirm the occurrence of delamination and observe via atomic force microscopy measurement a micron-scale delaminated patch in a system using chemical vapor deposition graphene. Furthermore, we show that the conductivity of the same system is strongly correlated to the area of delamination via coincident current measurements and optical imaging of the delaminated area. Finally, we demonstrate that delamination alone can cause a dramatic breakdown of barrier function through observation of a reversible increase in conductance of samples prepared with pristine defect-free graphene. These findings should have a great impact on the design and interpretation of 2D barrier material for both experiments and applications.\u3c/p\u3

Numerical investigation of micro- and nanochannel deformation due to discontinuous electroosmotic flow

Large pressures can induce detrimental deformation in micro- and nanofluidic channels. Although this has been extensively studied for systems driven by pressure and/or capillary forces, deflection in electrokinetic systems due to internal pressure gradients caused by non-uniform electric fields has not been widely explored. For example, applying an axial electric field in a channel with a step change in conductivity and/or surface charge can lead to internally generated pressures large enough to cause cavitation, debonding, and/or channel collapse. Finite electric double layers within nanofluidic channels can further complicate the physics involved in the deformation process. In order to design devices and experimental procedures that avoid issues resulting from such deformation, it is imperative to be able to predict deformation for given system parameters. In this work, we numerically investigate pressures resulting from a step change in conductivity and/or surface charge in micro- and nanofluidic channels with both thin and thick double layers. We show an explicit relation of pressure dependence on concentration ratio and electric double layer thickness. Furthermore, we develop a numerical model to predict deformation in such systems and use the model to unearth trends in deformation for various electric double layer thicknesses and both glass and PDMS on glass channels. Our work is particularly impactful for the development and design of micro- and nanofluidic-based devices with gradients in surface charge and/or conductivity, fundamental study of electrokinetic-based cavitation, and other systems that exploit non-uniform electric fields