Abstract: A method is disclosed for controlling the direction and transport of a material on a microfluidic device formed from an acrylic polymer, by electrokinetic flow of a fluid containing the material. The method comprises providing an electrokinesis buffer containing a charged hydrophilic polymer, wherein charges on the polymer are randomly distributed. The method has applications for improved transport of proteins and transport of materials comprising differentially charged chemical species. A preferred embodiment of the present invention comprises use of the disclosed method for electrokinetic separations of a mixture of polypeptides having both positive and negative charges. Another preferred embodiment concerns use of the disclosed method for performing an assay involving mixing of two or more reagents, wherein a first reagent comprises an enzyme and a second reagent comprises species having an opposite charge to the enzyme.

Abstract: This invention relates to a competitive-binding, capillary electrophoretic method of detecting new therapeutic regulatory (modulating) and diagnostic compounds in natural samples and other complex biological materials. The present method generally comprises mixing a preselected, detectable target with a sample of complex biological material to produce a first, sample/target mixture capillary electrophoresis apparatus. Subsequently, the first mixture is mixed with a pre-selected, tight-binding competitive ligand (TBCL), prior to produce a second, sample/target/TBCL mixture, for a predetermined optional incubation period sufficient to allow the TBCL to bind a pre-selected percentage of the available target in the absence of any other ligand. An aliquot of the second mixture is subsequently subjected to pre-optimized capillary electrophoresis, during which the migration of the target is monitored.

Abstract: Provided is an apparatus for separating, in a medium, a component from a composition comprising: (1) an array of three or more electrodes arrayed along a pathway along which molecules of the composition are transported; and (2) a power source device for delivering to voltage to the electrodes; wherein the voltages delivered to the electrode array by the power source device are effective to: (a) alter the relative movement along the transport pathway of two or more of the molecules caused by a motive force, or (b) cause the molecules to move along the transport pathway.

Abstract: A system and method is disclosed for chromatography and electrophoresis using circular optical scanning. One or more rectangular microchannel plates or radial microchannel plates has a set of analysis channels for insertion of molecular samples. One or more scanning devices repeatedly pass over the analysis channels in one direction at a predetermined rotational velocity and with a predetermined rotational radius. The rotational radius may be dynamically varied so as to monitor the molecular sample at various positions along a analysis channel. Sample loading robots may also be used to input molecular samples into the analysis channels. Radial microchannel plates are built from a substrate whose analysis channels are disposed at a non-parallel angle with respect to each other. A first step in the method accesses either a rectangular or radial microchannel plate, having a set of analysis channels, and second step passes a scanning device repeatedly in one direction over the analysis channels.

Abstract: The present invention provides methods for measuring endogenous heparin in a mammal at levels that were previously undetectable. The present invention further features methods for assessing the risk for and assessing the progression of atherosclerosis and methods for treating or inhibiting the progression of atherosclerosis. The invention also features methods for monitoring plasma heparin levels in subjects undergoing heparin treatment. Additionally, the present invention provides kits for assaying for heparin in biological samples.

Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.

Abstract: The present invention concerns devices, apparatus and methods for transferring liquids. One aspect of the present invention is a device comprising a plate having a plurality of transfer elements. Each of the transfer elements comprises an aperture in the plate where the aperture is capable of being electrically activated. The plate has one of more attaching elements for attaching the plate to a multiwell plate to form a sealed system except for the apertures of the transfer elements. Usually, the device is adapted for sealing attachment to a multiwell plate. In a method in accordance with the present invention a quantity of liquid is disposed to a second side of a plate having a plurality of apertures in the plate. The apertures are capable of being electrically activated. The liquid is present in a closed well except for the apertures in the plate. To simultaneously expel liquid from the apertures, the apertures are electrically activated.

Abstract: The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (10) including a microfabricated silicon chip (12) on a printed circuit board (14) and a flow cell (16) mounted to the chip (12) to form a flow chamber. The cartridge (10) also includes output pins (22) for electronically connecting the cartridge (10) to an electronic controller. The chip (12) includes a plurality of circular microelectrodes (24) which are preferably coated with a protective permeation layer which prevents direct contact between any electrode and a sample introduced into the flow chamber.

Abstract: An electrophoretic device and method for focusing a charged solute is disclosed. The device includes a first chamber for receiving a fluid medium, the first chamber having an inlet for introducing a first liquid to the chamber and an outlet for exiting the first liquid from the chamber; a second chamber comprising an electrode array, the second chamber having an inlet for introducing a second liquid to the chamber and an outlet for exiting the second liquid from the chamber; and a porous material separating the first and second chambers. The device's electrode array includes a plurality of electrodes and generates an electric field gradient profile which can be dynamically controlled. In the method, a charged solute is introduced into a fluid medium followed by the application of a hydrodynamic force. Opposing the hydrodynamic force with an electric field gradient results in solute focusing in the fluid medium.

Abstract: A proteome analyzer includes a separation cassette having a first dimension separation compartment for separation of protein samples by isoelectric focusing and a second dimension separation compartment for separation of protein samples by SDS-polymer network electrophoresis. The first dimension compartment is a reservoir in which a porous material having capillary channels is disposed. The protein samples are disposed in the capillary channels and, in the presence of a pH gradient, are focused spatially by isolectric focusing upon application of an electric field. The second dimension compartment consists of two glass or plastic plates separated by a separation medium. The separation medium is an ultra-thin layer of a low concentration linear polymer supported by an inert matrix. The spatially focused protein samples are contacted with the separation medium in the presence of an electric field to initiate second dimension separation.

Abstract: Chiral separations can be enhanced through the use of polymerized dipeptide-surfactant or oligopeptide-surfactant chiral micelles. Because polymerized micelles eliminate much of the complex dynamic behavior associated with conventional micelles, polymerized chiral micelles have stronger chiral recognition properties than do otherwise-identical, “conventional” or non-polymerized chiral micelles. Recovery of chiral ligands from polymerized chiral micelles is often easier, as the chiral ligands may typically be recovered by simple extraction with an appropriate organic solvent. By contrast, recovering the solute from a conventional, non-polymerized micellar medium by extraction with an organic solvent frequently results in the formation of troublesome emulsion systems. Polymerized chiral micelle systems are therefore beneficial in both preparative-scale and process-scale separations.

Abstract: Miniaturized planar column devices for use in a liquid phase separation apparatus are described. The devices include microstructures that have been fabricated by laser ablation in a variety of novel support substrates. Devices formed according to the methods of the invention include associated laser-ablated features required for function, such as on-device reservoirs or makeup flow compartments, analyte detection means and sample injection means. The miniaturized columns can be used in an apparatus intended for analysis of either small and/or macromolecular solutes in the liquid phase which employs chromatographic, electrophoretic or electrochromatographic separation means. The apparatus can include a variety of optional injection means, manifolds, keeper means, post column collection means, and combinations thereof.

Abstract: The behavior of particles is tested by placing a suspension of the particles in a chamber in which an electrode array is arranged to generate a spectrum of different frequency dielectrophoretic fields. The behavior of the particles at the different frequencies can be studied in a convenient and rapid manner. The apparatus and method can be used for a variety of purposes, including characterising the properties of specified particle types, or analysing the particle population in a fluid. It is also possible to expose the particles to different fluid parameters to extend the test spectrum in other senses.

Abstract: A fully integrated monolithic small volume PCR-CE device in glass, or the like materials, is fabricated using thin film metal heaters and thermocouples to thermally cycle sub-microliter PCR volumes. Successful amplification of a PCR fragment is demonstrated on a PCR-CE chip. The process utilizes a linear polyacrylamide surface coating coupled with addition of BSA to the amplification buffer was necessary to obtain amplification efficiencies comparable to a positive control. The micro-reactor reduced significantly the time required for amplification and the reaction volume was in the sub-microlitre regime. Likewise addressed are the known problems connected with reliable microfabrication of metal coatings and the insulating layers required to shield these layers from the PCR reaction mix, and the longstanding unresolved issue of exposed metal regions in the PCR-CE chip resulting in electrolysis of water and bubble formation whenever a voltage is applied.

Abstract: A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric filed within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule.

Abstract: A chip for performing an electrophoretic separation of micromolecular or macromolecular structures in two dimensions comprises a base substrate comprising a main surface. A channel is formed in the main surface of said base substrate in a first direction, wherein a first voltage is applicable across the channel in order to allow a separation of micromolecular structures or macromolecular structures in the first direction on the basis of a first separation mechanism. In addition, a two-dimensional separation matrix is formed in the main surface of the base substrate, wherein the separation matrix comprises a shallow recess and an array of stand-alone posts arranged in the recess. The recess extends perpendicular from the channel in a second direction, wherein a second voltage is applicable across the separation matrix in order to allow a separation of the structures on the basis of a second separation mechanism.

Abstract: Degradation of RNA present in a sample is detected by using, as an indicator, rRNA included in the RNA. The steps include: (a) introducing the sample onto a microchannel, at an introducing point, filled with an electrophoresis separation gel; (b) conducting electrophoresis of rRNA fragments present in the sample to force rRNA fragments to migrate through the electrophoresis separation gel; (c) detecting rRNA fragments passing through a detection point located downstream of the introducing point, to obtain detection patterns; and (d) determining degradation of RNA present in the sample based on the detection patterns of rRNA. A sample containing degraded mRNA can also be screened by detecting rRNA degradation in the above microchannel electrophoresis.

Abstract: The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.

Abstract: An adaptor for a multi-channel pipettor which allows the user to load multiple wells of a gel simultaneously using gel loading tips. The adaptor has apertures at the top which lead to channels which travel the length of the adaptor and exit at the bottom. Gel loading tips, already affixed onto a multi-channel pipettor, are inserted into the apertures at the top of the adaptor and the ends of the tips exit the adaptor through apertures at the bottom of the adaptor. The apertures at the bottom of the adaptor are spaced so that they match the spacing of wells for various gels.

Abstract: A multi-channel capillary electrophoresis apparatus is disclosed. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having a capillary outlet, and an outlet support for supporting the capillary outlets. The apparatus further includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot is adapted to removably receive the outlet support, and wherein when the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. In addition, the apparatus includes a front plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.