Abstract: High throughput liquid chromatography systems include multiple separation columns and multiple flow-through detection regions in sensory communication with a common radiation source and a multi-channel detector. Preferred detector types include a multi-anode photomultiplier tube, a charge-coupled device detector, a diode array, and a photodiode array. In certain embodiments, separation columns are microfluidic and integrated into a unitary microfluidic device. The optical path through a detection region is preferably coaxial with the path of eluate flow along a flow axis through a detection region. On-board or off-board detection regions may be provided.

Abstract: Systems and methods for performing multiple parallel chromatographic separations are provided. Microfluidic cartridges containing multiple separation columns allow multiple separations to be performed in a limited space by a single instrument containing high-pressure pumps and analyte detectors. The use of pressure fit interfaces allows the microfluidic cartridges to easily be removed and replaced within the instrument, either manually or robotically.

Abstract: Systems and method for removing undesirable gas from microfluidic separation devices to prepare them for operation are provided. The microfluidic devices contain separation media that provides a significant fluidic impedance. A vacuum source is used to evacuate gas from, and a positive pressure source is used to introduce liquid into, the microfluidic device to minimize the presence of undesirable bubbles. Where hydrophobic materials are present within the microfluidic device, the liquid may be an organic solvent. Positive pressures of at least about 100 psi are preferably employed. A microfluidic separation device may include multiple separation columns and a distribution network in fluid communication with the columns.

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: Systems and methods for collecting the output of multiple simultaneously operated chromatography columns and providing the outputs to a single mass spectrometer are provided. Such systems utilize predetermined lengths of microfluidic tubing that act as storage buffers for the substantially all of the output of each column, preserving all data and, because the storage buffers are microfluidic, there is minimal diffusion between sample bands and solvent and signal clarity is preserved.

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: 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: 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.

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: 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.

Abstract: 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.