A static mixer device comprising a housing having a proximal end, a distal end, and an opening extending between the proximal and distal ends. In certain embodiments, a plurality of metal frits is positioned within the opening of the housing, each of the metal frits extending across a cross-sectional dimension of the opening and having interconnected porosity. In other embodiments, one or more mixer elements fabricated using laser additive manufacturing technology and having novel configurations are positioned within the opening of the housing. In yet other embodiments, the housing comprises multiple openings having different diameters from each other, with each opening either extending through the housing with a constant diameter or with one or more of the openings having a varying diameter.

Systems and techniques are described for capturing target extracellular vesicles from a fluid sample. In some implementations, a microfluidic device includes a microfluidic channel where an internal surface of at least one wall of the microfluidic channel includes a plurality of grooves or ridges, or both grooves and ridges, arranged and configured to generate chaotic mixing within a fluid sample flowing through the microfluidic channel. The microfluidic device also includes a plurality of elongate flexible linker molecules, each having a molecular weight between about 1.8-4.8 kDa, where each elongate flexible linker molecule is bound at a first end to an internal surface of at least one wall of the microfluidic channel and is bound at a second end to one or more binding moieties that specifically bind to a target extracellular vesicle.

The present disclosure is directed towards improved systems and methods for large-scale production of nanoparticles used for delivery of therapeutic material. The apparatus can be used to manufacture a wide array of nanoparticles containing therapeutic material including, but not limited to, lipid nanoparticles and polymer nanoparticles. In certain embodiments, continuous flow operation and parallelization of microfluidic mixers contribute to increased nanoparticle production volume.

Provided are scalable, parallelized microfluidic chips that include arrays of microfluidic mixing channels for large-scale production of lipid nanoparticles, among other products. The disclosed chips can operate with a single set of inlets and outlet, and achieve production rates in excess of those achieved by existing methods. The disclosed devices provide large-scale production of formulations while still maintaining the physical properties and potency typical of existing methods of producing such formulations. Also provided are related methods of using the disclosed devices.

Described are chips for detecting a target in a sample including a microfluidic flow chamber comprising one or more flow channels having a capture surface and at least one micromixer. Described are methods of using this chip wherein targets are identified by total internal reflection fluorescence (TIRF).

Described are chips for detecting a target in a sample including a microfluidic flow chamber comprising one or more flow channels having a capture surface and at least one micromixer. Described are methods of using this chip wherein targets are identified by total internal reflection fluorescence (TIRF).

An example overfill-tolerant microfluidic structure can include an inlet microfluidic channel. A sample chamber can be connected to the inlet microfluidic channel to receive liquid from the inlet microfluidic channel. A gas-permeable liquid barrier can be connected to the sample chamber and positioned to allow gas to flow out of the sample chamber. An overflow chamber can be connected to the inlet microfluidic channel. A capillary break can be positioned between the inlet microfluidic channel and the overflow chamber. The capillary break can include a narrowed opening with a smaller width than a width of the inlet microfluidic channel. In some examples, the gas-permeable liquid barrier can allow gas to flow out of the sample chamber at a pressure lower than the break pressure, and prevent liquid from flowing out of the sample chamber at the break pressure.

Disclosed herein are fluidic mixers having bifurcated fluidic flow through toroidal mixing elements. The mixers operate, at least partially, by Dean vortexing. Accordingly, the mixers are referred to as Dean Vortex Bifurcating Mixers (DVBM). The DVBM utilize Dean vortexing and asymmetric bifurcation of the fluidic channels that form the mixers to achieve the goal of optimized microfluidic mixing. The disclosed DVBM mixers can be incorporated into any fluidic (e.g., microfluidic) device known to those of skill in the art where mixing two or more fluids is desired. The disclosed mixers can be combined with any fluidic elements known to those of skill in the art, including syringes, pumps, inlets, outlets, non-DVBM mixers, heaters, assays, detectors, and the like.

The present disclosure is directed towards improved systems and methods for large-scale production of nanoparticles used for delivery of therapeutic material. The apparatus can be used to manufacture a wide array of nanoparticles containing therapeutic material including, but not limited to, lipid nanoparticles and polymer nanoparticles. In certain embodiments, continuous flow operation and parallelization of microfluidic mixers contribute to increased nanoparticle production volume.

A closed-system flow cell system featuring an encasement with an inner cavity adapted to hold a slide and form a channel atop the slide. The encasement comprises a groove pattern within the channel, wherein the groove pattern provides a chaotic advection regime to fluid within the channel. The flow cell system helps enhance fluid mixing and prevent reagent evaporation and drying out of the tissue.