The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five-layer model including a first and second microchannel with a membrane-gel layer-membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.

Acoustophoretic devices and methods for separating biological cells (particularly T-cells) from other fluids/materials using multi-dimensional acoustic standing waves are disclosed. The devices include an inlet, at least two outlets, and a flow chamber having an ultrasonic transducer-reflector pair. Specifically, T cells, B cells, or NK cells can be separated from other blood components. A dual-pass acoustophoretic system including two acoustophoretic devices arranged in series and fluidly connected to one another is also illustrated. Means for pre-chilling the mixture prior to separation in the devices or system can be used to improve retention, concentration, and clarification and to prevent outgassing.

Apparatus for processing liquids or liquid-based substances includes a plurality of volumes at least two of which are defined at least in part by one or more phaseguides inside the volume and/or in a conduit connected thereto for controlling aliquoting of one or more liquids or liquid-based substances inside the volume. Each volume has an upstream and downstream side with respect to meniscus advancement direction via which it may be filled with or emptied of one or more liquids or liquid-based substances. The apparatus also includes at least one common upstream-side conduit connected to supply a liquid or liquid-based substance via a plurality of the inlet or extraction conduits, a plurality of the phaseguides exhibiting a predetermined level of stability and one or more of the phaseguides exhibiting a predetermined different stability compared with the stability of at least one of the other phaseguides whereby to control the preference order in which the volumes fill and/or empty. The stability is determined by the value and radius of an acute angle along a said phaseguide at the downstream side of the phaseguide.

A device for assembling aggregations of adherent cells includes a gripper moveable within an assembly vessel that fixes aggregations of adherent cells at a membrane of the gripper and, by movement of the gripper, assembles aggregations of cells on a separate membrane within the vessel, thereby creating a three-dimensional assembly of aggregations of cells that fuse and can be employed in surgical procedures as a unitary tissue of adherent cells. The aggregations of cells, as assembled, can assume three-dimensional configurations distinct from any one of the component aggregations of cells assembled.

An inverted microwell provides rapid and efficient microanalysis system and method for screening of biological particles, particularly functional analysis of cells on a single cell basis. The use of an inverted open microwell system permits identification of particles, cells, and biomolecules that may be combined to produce a desired functional effect also functional screening of secreted antibody therapeutic activity as well as the potential to recover cells and fluid, and optionally expand cells, such as antibody secreting cells, within the same microwell.

A skin organ culture model system is provided having a perfusion plate (1), a peristaltic pump (2), and a culture reservoir (3). The skin organ culture model system combines both the dynamic perfusion of culture medium with the use of plasma as culture medium in order to provide, in the model system, culture conditions that are similar to in vivo conditions.

A composition comprising a first material and a second material, wherein said first material is cross-linkable by a first cross-linking reaction and said second material is cross-linkable by a second cross-linking reaction, wherein said first cross-linking reaction and said second cross-linking reaction are inducible by a common activator.

Microfluidic devices, systems, and methods providing for an invasion assay using microfluidic culture systems.

Production of etanercept using perfusion methods achieves attractive yields of properly folded protein. Desired temperature, feed media, titers and percent correctly folded protein are disclosed.