Nanostream, Inc.

Paren P Patel

Christoph D Karp

Steven E Hobbs

Jeffrey Alan Koehler

Stephen D O'Connor

Marci Pezzuto

Joseph F Covington

Eugene Dantsker

Matthew M Gregori

Mark S Scheib

Scott G Beach

Chromatographic separation devices include multiple batch-processed columns joined by a body structure and adapted to perform parallel analyses. Both slurry-packed and monolithic column embodiments are provided. One or more liquid-permeable frits of various types may be used to retain stationary phase material within columns. A fluidic distribution network may be used to distribute stationary phase material and/or mobile phase solvents to multiple columns. Separation devices, including microfluidic embodiments, may be fabricated with various materials including polymers. Multi-column fabrication and separation methods are provided.

Multi-column separation devices and methods

A multi-layer microfluidic separation device comprises a polymeric membrane frit that may be securely bonded within the device and minimizes lateral wicking. Stationary phase material having an average particle size is retained by a frit having an average pore size that is smaller than the average particle size. In one embodiment, a secure bond is ensured by treating the polymer to match its surface energy to that of the materials to which it is bound. Treatments include plasma treatment, irradiation and the application of acids.

Frit material and bonding method for microfluidic separation devices

Microfluidic analytical devices and systems have at least one porous element disposed downstream of one or more optical detection regions in a pressure-based separation system. A porous element elevates the backpressure within an optical detection region, thus suppressing bubble formation and enhancing optical detection. Various types of porous elements include porous membranes, packed particulate material, and polymerized monoliths. Preferred devices may be fabricated with substantially planar device layers, including stencil layers, that are directly bonded without adhesives to form a substantially sealed microstructure suitable for performing pressure-based chromatographic separations at elevated operating pressures and with organic solvents.

Pressurized microfluidic devices with optical detection regions

Microfluidic devices capable of efficiently mixing two or more fluid are provided. Two or more microfluidic inlet channels defined in different sheets of material meet at an overlap region in fluid communication with an outlet channel. The channels are defined through the entire thickness of stencil sheets. The overlap region may include an aperture-defining spacer layer, and/or an impedance element, such as a porous membrane, adapted to distribute at least one fluid across the entire width of the outlet channel to promote reliable fluid mixing.

Fluidic mixer in microfluidic system

Pressure-driven microfluidic separation devices, such as may be used for performing high performance liquid chromatography, are provided. Multiple separation columns may be defined in a single device and packed with stationary phase material retained by porous frits. One or more splitters may be provided to distribute slurry and/or mobile phase among multiple separation columns. In one embodiment, separation devices are substantially planar and fabricated with multiple device layers. Systems and methods employing slurry for packing separation devices are also provided.

Separation column devices and fabrication methods

A method for fabricating a microfluidic device where first and second substantially flat platens are provided. Multiple substantially planar, substantially metal-free, adhesiveless polymer device layers, the device layers including a first cover layer, second cover layer, and at least one stencil layer defining a microfluidic channel penetrating through the entire thickness of the stencil layer also are provided. Each stencil layer is disposed between other device layers such that the channel is bounded laterally by a stencil layer, and bounded from above and below by surrounding device layers to define an upper channel surface and a lower channel surface. The device layers are stacked between the first platen and the second platen. The stacked device layers are controllably heated according to a heating profile adapted to form a substantially sealed adhesiveless microfluidic device wherein each upper channel surface remains distinct from its corresponding lower channel surface. The resulting microfluidic device has high inter-layer bond strength while preserving the integrity of the channel(s) defined in the stencil layer(s).

Adhesiveless microfluidic device fabrication

A frit for use in multi-layer microfluidic separation devices is provided. The frit comprises a polymeric membrane that may be securely bonded within the device and minimizes lateral wicking. A secure bond is ensured by treating the polymer to match its surface energy to that of the materials to which it is bound. Treatments include plasma treatment, irradiation and the application of acids.

A microfluidic reactor for performing chemical and biological synthesis reactions, including chemical and biological syntheses of organic, polymer, inorganic, oligonucleotide, peptide, protein, bacteria, and enzymatic products is provided. Two fluids are input into the device, mixed in a mixing region and provided to a long, composite reaction channel. Fluids flowing through the reaction channel may be diverted at a diversion region into a sample channel. Fluids in the sample channel may be mixed at a second region, with additional reagents.

Microfluidic synthesis devices and methods

Microfluidic devices for splitting an established fluidic flow through a microfluidic channel among multiple downstream microfluidic channels include a plurality of elevated flow resistance regions to promote precise and predictable splitting. Each elevated resistance region imparts a flow resistance that is substantially greater than the characteristic resistance to established flow of its associated downstream channel. Elevated flow resistance regions may include one or more porous materials and/or alterations to the channel geometry of at least a portion of a downstream channel.

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Sierra Madre, CA, United States of America

Paren P Patel