Nanostream, Inc.

Marci Pezzuto

Stephen D O'Connor

Eugene Dantsker

Christoph D Karp

Steven E Hobbs

Paren P Patel

Jeffrey Alan Koehler

Mark S Scheib

Joseph F Covington

Courtney Coyne

Microfluidic devices capable of combining discrete fluid volumes generally include channels for supplying different fluids toward a sample chamber and means for establishing fluid communication between the fluids within the chamber. Discrete fluid plugs are defined from larger fluid volumes before being combined. Certain embodiments utilize adjacent chambers or subchambers divided by a rupture region such as a frangible seal. Further embodiments utilize one or more deformable membranes and/or porous regions to direct fluid flow. Certain devices may be pneumatically or magnetically actuated.

Microfluidic systems and methods for combining discrete fluid volumes

A threadless interface for a fluidic system includes a microfluidic device having an outer surface and an internal near-surface channel having a first width and disposed at a first depth relative to the outer surface, with the first width being less than about two times the first depth. A fluidic seal engages the outer surface and exerts an elevated contact pressure against at least a portion of the outer surface without substantially occluding the channel. A preferred seal includes a raised boss. A fault tolerant flow path design can accommodate misalignment between adjacent device layers without detrimentally affecting fluid flow capability. The interface may be used in a microfluidic system for performing parallel analyses such as high performance liquid chromatography.

Sealing interface for microfluidic device

Modular microfluidic systems includes a plurality of microfluidic modules, each capable of performing fluidic operations including, but not limited to, filtering, splitting, regulating pressure, mixing, metering, reacting, diverting, heating, cooling, and condensing are provided. The microfluidic modules are polymeric, stencil-based structures adapted to be coupled in sequence for performing biological or chemical synthesis, including, but not limited to, chemical and biological syntheses of organic, polymer, inorganic, oligonucleotide, peptide, protein, bacteria, and enzymatic products.

Microfluidic analytical devices and 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 modular microfluidic system includes a plurality of discrete microfluidic modules each capable of performing at least one operation and at least one microfluidic coupling device for fluidically coupling the modules to perform a sequence of operations. The microfluidic modules and coupling devices may be constructed according to various techniques. In one embodiment, coupling devices are fabricated from multiple layers and each include a fluidic inlet port, a fluidic outlet port, and at least one sandwiched stencil layer having a microfluidic channel formed therein. Also described are integrated microfluidic systems and methods capable of performing various sequences of operations.

Modular microfluidic systems

Microfluidic systems and devices having integrated fluidic impedances are provided. Such impedances hinder the passage of fluid at low differential pressures, but allow fluid flow at higher differential pressures. Impedances are formed at the overlap of two or more microfluidic channels contained in different layers of a device. Such devices can be rapidly prototyped and can be assembled to contain multiple fluidic impedances to perform complex fluid handling tasks, including the metering of small aliquots from a larger fluid volume. Various means may be used to overcome the fluidic impedances.

Microfluidic systems with inter-channel impedances

Microfluidic devices having porous materials that restrict fluid flow rate for a given pressure are provided. Multiple porous regions can be constructed in a single device so that they have different valving capabilities or impedances, and in unison can control the overall direction of fluid flow. Porous regions can be constructed in various ways, such as, for example: by inserting porous materials into or between channels; by sandwiching one or more sheets or layers of porous materials between other layers of a device; or by inserting a liquid, solution, slurry, or suspension into a microfluidic channel and then permitting the formation of porous deposits by promoting at least partial evaporation. Adhesive tape may be used for one or more layers of such a microfluidic device.

Microfluidic devices with porous regions

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

The invention provides microfluidic devices with embedded fluidic impedances. Such impedances do not allow fluid to pass at a low differential pressure, but allow fluid to flow at a higher differential pressure. Impedances are formed by the three dimensional overlap of two or more channels contained within layers of the device. Such devices can be rapidly protyped and can be assembled to contain multiple fluidic impedances to perform complex fluid handling tasks, including metering defined volumes of samples and dividing samples into aliquots.

Fluidic impedances in microfluidic system

Microfluidic coupling devices capable of connecting more than one microfluidic module together to form a larger, integrated system are described. These devices are constructed in a number of ways. In a certain embodiments, the coupler is constructed from laminated materials and mates to one or more microfluidic devices using adhesive. The device can be used to place fluid into a microfluidic device, to remove fluid from a microfluidic device, or to transfer fluid between two or more microfluidic devices. Also described are modular microfluidic systems formed from microfluidic modules made using various techniques and/or useful for performing various functions.

Fluidic couplers and modular microfluidic systems

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.

Flow control in multi-stream microfluidic devices

Microfluidic devices and methods for metering discrete plugs of fluid are provided. The microfluidic devices include a trunk channel and a branch channel having an impedance region. A fluid is supplied to the trunk channel and fills the branch channel to the impedance region. The fluid is then flushed from the trunk channel leaving the branch channel filled. Because the branch channel has a volume, a discrete plug of the fluid having a volume substantially equal to that of the branch channel is formed.

Microfluidic branch metering systems and methods

Microfluidic devices having porous membrane valves, which are microfluidic channels or elements having porous materials that restrict fluid flow rate for a given pressure, are provided. Multiple microfluidic valves of this invention can be constructed on a single device so that they have different valving capabilities or impedances, and in unison can control the overall direction of fluid flow. Impedance regions may be constructed in various ways, such as, for example: by inserting porous materials into or between channels; by sandwiching a sheet or layer of porous material between other layers of the device (preferably in stencil form); or by inserting a liquid, solution, slurry, or suspension into microfluidic channels, and then permitting the formation of porous deposits by promoting at least partial evaporation. Adhesive tape may be used for one or more layers of the device.

Growing community of inventors

Altadena, CA, United States of America

Marci Pezzuto