Abstract: Microfluidic devices including one or more microstructures adapted to provide an indication of the extent and severity of collapse of channels and other microstructures within the device are provided. The channel collapse test structures do not communicate with operational structures of the device, but are positioned and adapted to provide an indication of the structural integrity of similarly dimensioned operational structures.

Abstract: 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.

Abstract: 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.

Abstract: Microfluidic devices including detection channel geometries that facilitate alignment such detection channels with multiple external sensors are provided. The detection channels include fault tolerant detection channels segments that have a span proportional and parallel to any anticipated positional or dimensional variation of the detection channels with respect to the positions of the multiple external sensors. The detection channels have a substantially constant channel width to minimize pressure-driven channel distortion and dead volumes.

Abstract: A connector for a stencil-based microfluidic device is provided. A planar substrate is affixed to the stencil-based microfluidic structure. A nipple is formed in the substrate. The tip of the nipple is flush with or recessed from the surface of the substrate to avoid interference with fabrication tools and processes.

Abstract: Microfluidic separators for separating multiphase fluids are described. Two or more microfluidic outlet channels within the device meet at an overlap region. The overlap region may be in fluid communication with an inlet channel. The inlet channel and each outlet channel are disposed within different layers of a three-dimensional device. Each channel is defined through the entire thickness of a stencil layer. A multiphase fluid flows through an inlet channel into an overlap region from where the separated phases can be withdrawn through the outlet channels.

Abstract: Microfluidic devices and methods for metering discrete plugs of fluid are provided. The microfluidic devices include an actuating channel, a metering channel and a deformable membrane disposed therebetween. The metering channel is in fluid communication with a fluid source, but is otherwise closed. The pressure in the actuating channel is varied to deform the deformable membrane. The volume of the metering channel varies in proportion with the deformation of the deformable membrane, creating a pressure differential between the metering channel and the fluid source. The pressure differential causes fluid from the fluid source to be drawn into or expelled from the metering channel.

Abstract: A pressure-driven microfluidic device for separating chemical or biological species from a sample provides on-column sample injection from a sample loading segment, with mobile phase solvent supplied to both the separation column and the sample loading segment to promote high-quality separation. Multiple separation channels each having an associated sample loading segment may be provided in a single device, with a first mobile phase solvent being supplied to an upstream portion of each separation channel via a first channel network and a second mobile phase solvent being supplied to each sample loading segment via a second channel network. Methods for operating pressure-driven microfluidic separation devices include the steps of supplying a sample to a sample loading segment and flowing mobile phase solvent an associated separation channel upstream of the sample loading region.

Abstract: Microfluidic fluid control devices are provided. One microfluidic fluid control device can be used as a uni-directional valve within a microfluidic system. The invention also provides a microfluidic pump mechanism having two unidirectional valves separated by an expandable reservoir. Such devices may be formed in multiple layers and utilize flexible membranes.

Abstract: 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.

Abstract: Substantially sealed microfluidic devices for performing pipettorless ratiometric dilution are provided. In one embodiment, valves are disposed between and permit selective fluid communication between multiple chambers of a series of chambers. In another embodiment, a mixing chamber receives fluid from an inlet port and is in donative fluid communication with multiple receiving chambers each having a small volume than the mixing chamber. Active mixing means may be provided, including moveable magnetic elements, sonication, and mixing channels coupled with fluid transport means. A material transport system may be used with a non-electrokinetic pipettorless dilution system for transporting sample, diluent, and combinations thereof within the device.

Abstract: Various microfluidic flow control devices are provided. In one embodiment, a regulating device includes overlapping channel segments separated by a deformable membrane in fluid communication with one another. In another embodiment, a normally open microfluidic valve provides latching valve operation with at least one adhesive surface. A stencil-based microfluidic valve may be operated by deforming a membrane against a seating surface to prevent flow through an aperture. Configurable microfluidic devices permit flow control among an interconnected microfluidic channel network. Magnetic elements may be integrated into flexible membranes to provide magnetically actuated microfluidic flow control device.

Abstract: Microfluidic flow control devices are provided. In one embodiment, a regulating device includes overlapping channel segments separated by a deformable membrane in fluid communication with one another. Pressure differentials between the channel segments deform the membrane towards the channel with the lower pressure, thereby restricting flow.

Abstract: A splitter for multi-layer microfluidic devices is provided. The splitter includes multiple forked channels defined in two or more device layers. The forked channels communicate fluidically at overlap regions. The overlap regions, in combination with symmetrical channel geometries balance the fluidic impedance in the system and promote even splitting.

Abstract: 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.

Abstract: Robust microfluidic mixing devices mix multiple fluid streams passively, without the use of moving parts. In one embodiment, these devices contain microfluidic channels that are formed in various layers of a three-dimensional structure. Mixing may be accomplished with various manipulations of fluid flow paths and/or contacts between fluid streams. In various embodiments, structures such as channel overlaps, slits, converging/diverging regions, turns, and/or apertures may be designed into a mixing device. Mixing devices may be rapidly constructed and prototyped using a stencil construction method in which channels are cut through the entire thickness of a material layer, although other construction methods including surface micromachining techniques may be used.

Abstract: 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.

Abstract: Systems and methods for metering microfluidic volumes are provided. A discrete plug may be separated from a larger volume of first fluid by injecting a second fluid, such as a gas, into a channel containing the first fluid. The injection of the second fluid to isolate the desired amount of the first fluid may be controlled through timing of flows, visual indicators and/or automated control systems using optical or electrical sensors.

Abstract: 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.

Abstract: Multi-layer microfluidic devices incorporating a filter element are provided. A filter element is compressively restrained between device layers, such that the compression promotes a tight seal between device layers and resists fluid leakage around the filter element.