Nanostream, Inc.

Eugene Dantsker

Stephen D O'Connor

Christoph D Karp

Marci Pezzuto

Steven E Hobbs

Paren P Patel

Mike S Lee

Adrian Hightower

Courtney Coyne

Surekha Vajjhala

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

Systems and methods are provided for preparing samples for chromatographic separations and then chromatographically separating the prepared samples, preferably in a high-throughput fashion utilizing multiple parallel first (fluid) processing regions in fluid communication with multiple parallel second (fluid) processing regions wherein the each second processing region includes a chromatography column. One or more common fluid supplies may be utilized in each of the sample preparation and separation steps to minimize the number of requisite fluid connections and external components such as pumps, reservoirs, pulse dampers, flow controllers, and the like.

Sample preparation for parallel chromatography

Fluidic systems, including microfluidic systems, are used to manipulate light by light-fluid interaction so as to affect reflection, refraction, absorption, optical filtering, or scattering of the beam. One or more fluids may be provided to a channel or chamber and exposed to an incident beam, and the proportion of at least one of a plurality of fluids may be varied. Light may interact with a discrete fluid plug subject to movement within a channel. One or more flexible members may be employed, such as to provide a variable lens. Fluidic optical devices may be used in applications including optical switching, optical filtering, or optical processing. Multiplexed fluidic optical systems are further provided.

Optical devices with fluidic systems

Microfluidic devices having a plurality of functional features for performing one or more fluidic operations in parallel are provided. Reagents, samples or other fluids common to multiple functional features ('common fluids') may be input into a microfluidic device or system through one or more distributing inputs that divide and distribute the common fluids as desired. The use of a multi-layer fabrication technique allows multiple distributing inputs to distribute to multiple functional features in a microfluidic device without undesirable fluid channel intersections.

Microfluidic devices with distributing inputs

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

Microfluidic devices with multiple fluid process regions for subjecting similar samples to different process conditions in parallel are provided. One or more common fluid inputs may be provided to minimize the number of external fluid supply components. Solid materials such as chromatographic separation media or catalyst media is preferably provided in each fluid process region. Solid materials may be supplied to the devices in the form of slurry, with particles retained by porous elements or frits. Different fluid process regions may having different effective lengths, different solid material types or amounts, or may receive different ratios of common fluids supplied to the device. The flow resistances of dissimilar fluid process regions may be balanced passively with the addition of impedance elements in series with each fluid process region.

Microfluidic devices for methods development

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

A microfluidic flow control device includes a fluidic chamber, a first and a second microfluidic channel, at least one sealing surface between the first and the second channels, and a floating element disposed within the chamber. The floating element is capable of intermittently engaging the sealing surface, and movement of the floating element affects fluid flow between the first channel and the second channel. The floating element may be moved by fluid pressure, gravity, or an applied force such as a magnetic field. Multiple flow control regions may be integrated into a flow control system.

Microfluidic flow control device with floating element

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

In accordance with the present invention there is provided a microfluidic heat exchange system for cooling heat-generating components of electronic equipment, computers, lasers, analytical instruments, medical equipment and the like. Both direct contact and indirect contact microfluidic systems are described. Also described are microfluidic systems that incorporate remote heat rejection systems that may be located outside the body of the equipment that contains the heat generating components that need cooling.

Microfluidic devices for heat transfer

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.

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Sierra Madre, CA, United States of America

Eugene Dantsker