Abstract: 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.

Abstract: 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.

Abstract: Systems and methods for analyzing a plurality of samples in parallel include a plurality of liquid phase separation regions, a plurality of microfluidic storage regions, and a common mass spectrometer. Samples are separated in parallel in the separation regions to yield a plurality of output streams that are stored in the storage regions. The contents of each storage region, or at least a representative portion thereof, are sequentially discharged, ionized, and directed to the inlet of a mass spectrometer. In this manner, multiple separations are conducted in parallel with outputs provided serially to a common mass spectrometer without any loss of data. Microfluidic storage regions minimize diffusion between bands of separated samples. Portions of separated samples may be directed to fraction collectors.

Abstract: A parallel fluid processing system including multiple fluid process regions containing solid material in fluid communication with a common first fluid source may be used to conduct analyses and/or synthesis in parallel. A parallel fluid processing data correction method includes supplying and processing a calibrant in each fluid process region, measuring a first physical parameter and deriving at least one correction factor based on the parameter, supplying and processing at least one second fluid in each fluid process region, and then applying the correction factor to yield corrected process data. Retention time correction, peak area correction, and other useful data corrections may be performed. Parallel fluid processing may be performed with microfluidic devices and systems. A system for correcting retention times in parallel liquid chromatography is further provided.

Abstract: 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.

Abstract: High throughput analytical systems and methods employing multiple liquid phase separation process regions coupled to a common mass spectrometer are provided. Disclosed systems and methods permits parallel separation and parallel storage of discrete eluate fractions, followed by sequential discharge and ionization of previously stored eluate portions to yield a composite ion stream containing the sequential series of eluate portions, followed by mass analysis of the ion stream. A common manifold may receive ions and utilize pressurized gas or ion gating to direct ions within the manifold toward the mass spectrometer inlet.

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: 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.

Abstract: 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.

Abstract: 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.

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: Systems for analyzing multiple samples in parallel using mass spectrometric preferably coupled with fluid phase separation techniques are provided. A multi-analyzer mass spectrometer includes multiple inlets, multiple mass analyzers, and multiple transducers to conduct mass analyses of multiple samples in parallel. A modular mass analyzer may include a vacuum enclosure, a chassis, and multiple mass analysis modules disposed within the chassis. Modules are preferably disposed in a spatially compact two-dimensional array. A common multi-stage vacuum system may be utilized in conjunction with baffles or partitions disposed within and between modules to maintain differential vacuum conditions within the spectrometer utilizing a minimum number of pumps. Common control inputs may be provided to multiple modules or other components within a multi-analyzer spectrometer.

Abstract: 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.

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: A first multi-channel optical flow cell includes a two end blocks disposed around a channel-defining flow layer, with a first end block having multiple inlet ports each containing an associated optical fiber and fluid conduit terminated substantially flush against an inner surface of the first end block. The second end block may have multiple outlet ports each containing at least one of an additional optical fiber and additional fluid conduit. A method for fabricating a multi-channel flow cell includes inserting a first plurality of optical fibers and a first plurality of fluid conduits through a plurality of inlet ports defined in a first end block, sealing the optical fibers and conduits, polishing the optical fibers, and then positioning and joining a channel-defining flow layer between the first end block and a second end block.

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: 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: 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: 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.

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.