Abstract: Methods and apparatuses for discriminating matter utilizing dielectrophoresis combined with magnetophoresis. A sample having one or more constituents is injected into an inlet port of a chamber. A carrier medium flow is initiated at the inlet port to establish a flow within the chamber. A dielectrophoretic force is generated to act on the constituents of the sample. A magnetophoretic force is generated to act on the constituents of the sample. The dielectrophoretic force and magnetophoretic forces are balanced to position the constituents within the chamber. The constituents are then collected at one or more outlet ports of the chamber according to the dielectric and magnetic characteristics of the constituents. The constituents may be collected as a function of time-of-exit from the chamber and/or position within the chamber.

Abstract: Systems, apparatuses and methods for cell isolation and analysis. Cells are introduced into a dielectrophoretic prefilter including one or more trapping electrodes configured to trap at least a portion of the cells with a dielectrophoretic force. The cells trapped from the prefilter are directed into a dielectrophoretic field-flow fractionation separator coupled to the prefilter. The cells are discriminated by balancing a dielectrophoretic force (and optionally a magnetophoretic force) with a gravitational force to displace the cells to positions within a velocity profile in the separator. At least a portion of the cells are trapped as a function of the cells' time of emergence from the separator with two or more spiral electrode segments coupled to the separator.

Abstract: A method and apparatus for microfluidic processing by programmably manipulating a packet. A material is introduced onto a reaction surface and compartmentalized to form a packet. A position of the packet is sensed with a position sensor. A programmable manipulation force is applied to the packet at the position. The programmable manipulation force is adjustable according to packet position by a controller. The packet is programmably moved according to the programmable manipulation force along arbitrarily chosen paths.

Abstract: Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome. Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive. These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (e.g. dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths. Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments.

Abstract: The present invention provides a novel active micro-mixer device and methods using electrohydrodynamic (EHD) convection. At least two fluid samples are introduced into a microchannel device wherein the surface charges are induced at the interface of the liquid samples that have different electric conductivities, and these surface charges react with applied electric fields to generate electric shear forces. By applying electric fields, the separate flow streams get mixed passing the electrodes. A new active micro-mixer for liquid/liquid mixing has been designed, fabricated, and demonstrated by flowing two liquid samples through the microchannel. The device can be used in the nano- or pico-liter range of liquid volumes by applying a low voltage across the microchannel. The micro-mixing device invented in this work has simple structure and no mechanical moving part, which can provide a reliable mixing function on biochips.

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. Specific cells from various cell mixtures were separated, lysed, and enzymatically digested on the chip.

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 method is disclosed for moving, isolating and/or identifying particles in a sample by placing said sample in a spatially varying electrical field wherein the spatially varying electrical field is following a mathematical nonmonotonous function, selected from the group consisting of linear, hyperbolic, parabolic, parabolic functions or y˜xp/q and combinations thereof wherein p q means an integer. Also various devices are disclosed for performing the method.

Abstract: A method and apparatus for microfluidic processing by programmably manipulating a packet. A material is introduced onto a reaction surface and compartmentalized to form a packet. A position of the packet is sensed with a position sensor. A programmable manipulation force is applied to the packet at the position. The programmable manipulation force is adjustable according to packet position by a controller. The packet is programmably moved according to the programmable manipulation force along arbitrarily chosen paths.

Abstract: Microfluidic devices for performing integrated reaction and separation operations. The devices include a planar substrate having a first surface with an integrated channel network disposed therein. The reaction region in the integrated microscale channel network has a mixture of at least first and second reactants located therein, wherein the mixture interacts to produce one or more products. The reaction region is configured to maintain contact between the first and second reactants contained within it. The device also includes a separation region in the integrated channel network, where the separation region is configured to separate the first reactant from the product, when the first reactant and product are flowing through the separation region. The conductivity of a fluid in the reaction region is higher than the conductivity of a fluid in the separation region.

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 device for the integrated micromanipulation, amplification, and analysis of polyelectrolytes such as DNA comprises a microchip which contains electrodes for dielectrophoresis powered by an AC signal generator, and a trapping electrode attached to a direct current source that can be heated to specific temperatures. Nucleic acids can be heated and cooled to allow for denaturation, the annealing of complementary primers and enzymatic reactions, as in a thermocycling reaction. After such a reaction has been completed on the trapping electrode, the dielectrophoretic field can be switched to a direct current to release the product and direct it through a matrix for fractionation and/or analysis. The device includes data analysis equipment for the control of these operations, and imaging equipment for the analysis of the products. The invention permits the efficient handling of minute samples in large numbers, since reactions occur while sample material is positioned on an electrode in a microfluidic channel.

Abstract: An apparatus for promoting reactions between particles suspended in a liquid is provided. The apparatus includes a treatment cell having an electrode array. The suspension of the particles is fed to the treatment cell by feeding means. The liquid is removed from the treatment cell by removing means. The feeding means is connected to the electrode array in the cell and adapted to generate a first non-uniform electrical field, at a first frequency, within the cell. The removing means is connected to the electrode array in the cell and adapted to generate, within the cell, a second non-uniform electrical field, at a second frequency which is different from the first frequency. The apparatus further includes means for simultaneously applying at least the first non-uniform electrical field, at the first frequency, and the second non-uniform electrical field, at the second frequency.

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 field 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: Disclosed is a process for manipulating microscopic dielectric particles in which particles are exposed to an electric field. In disadvantaged processes the particles are exposed to inhomogeneous electric field and are polarized by them. The polarized particles are moved in the direction of higher field strength. These processes permit no reversal of the traveling direction of the particles. The particles are enriched at the electrode so that they cannot be retained in free space. In the invented process the particles are exposed to high-frequency field traveling in one or more prescribed direction, by which the particles are subject to a force which sets them in a motion that is strongly synchronous to the field. With the aid of a device for carrying out the invented process, the particles can be manipulated very flexibly.

Abstract: An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing and temperature profile scheme. The apparatus includes a cuvette holder with a Peltier device forming part of the electrode structures that form part of the holder. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells.

Abstract: A micromachined system for electrical field-flow fractionation of small test fluid samples is provided. The system includes a microchannel device comprising a first substrate having a planar inner surface with an electrode formed thereon. A second substrate having a planar inner surface with an electrode formed thereon is positioned over the first substrate so that the respective electrodes face each other. An insulating intermediate layer is interposed between the first and second substrates. The intermediate layer is patterned to form opposing sidewalls of at least one microchannel, with the electrodes on the substrates defining opposing continuous boundaries along the length of the microchannel. Inlet and outlet ports are formed in one or both substrates for allowing fluid flow into and out of the microchannel. The microchannel device can be fabricated with single or multiple microchannels therein for processing single or multiple test fluids.

Abstract: An ultra-miniaturized surface structure with controllable adhesion having extremely miniaturized (in the sub atomic range) planar electrode strips applied to the surface to which high frequency pulse trains may be applied to generate progressive or stationary standing waves. The electrodes in themselves are combined with dielectric insulating materials with controlled bio-compatibility. The type of electric drive, together with the properties of the surface layers that cover the electrodes, determines the adhesion properties of the surface to a large extent regardless of the used base material. Particle movement is gently influenced, so that for the first time it becomes possible to influence particles in highly physiological nutritive solutions.

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: Travelling wave particle separation apparatus is provided having a flat spiral of electrodes (1,2,3,4) or a helix of similar electrodes on a cylindrical former. Only four electrical connections need to be made.

Abstract: A method and a device for position and/or type-selective control of the position and/or change of position of suspended particles in a multielectrode system by the effect of polarization forces that are induced in the particles by alternating electric fields in the multielectrode system, which particles comprise biological or synthetic objects with dimensions essentially corresponding to those of biological cells or cell organelles, viruses or macromolecules, base on the fact that the multielectrode system forms with the particle suspension an electrical network, in which means of resonance are provided for creating a resonant increase or damping of the field strength of the alternating electric fields at certain frequencies in at least one locally demarcated region of the multielectrode system.

Abstract: Particles are subjected to travelling wave field migration (TWFM) to migrate the particles over an array of microelectrodes. Altered particles are produced by treating original particles in such a way so as to alter their TWFM characteristics and the altered TWFM characteristics are employed for analysis and/or separation of the altered particles. The particles may be cells, bacteria, viruses, biomolecules or plastics microspheres. They may be altered by binding to a ligand such as a metal microparticle via a selective linking moiety such as an antibody/antigen or oligonucleic acid, or be physical or chemical treatments.

Abstract: The present disclosure is directed to a novel apparatus and novel methods for the separtion, characterization, and manipulation of matter. In particular, the invention combines the use of frequency-dependent dielectric and conductive properties of particulate matter and solubilized matter with the properties of the suspending and transporting medium to discriminate and separate such matter. The apparatus includes a chamber having at least one electrode element and at least one inlet and one output port into which cells are introduced and removed from the chamber. Matter carried through the chamber in a fluid stream is then displaced within the fluid by a dielectrophoretic (DEP) force caused by the energized electrode. Following displacement within the fluid, matter travels through the chamber at velocities according to the velocity profile of the chamber. After the matter has transitted through the chamber, it exits at the opposite end of the chamber at a characteristic position.

Abstract: The present disclosure is directed to a novel apparatus and novel methods for the separation, characterization, and manipulation of matter. In particular, the invention combines the use of frequency-dependent dielectric and conductive properties of particulate matter and solubilized matter with the properties of the suspending and transporting medium to discriminate and separate such matter. The apparatus includes a chamber having at least one electrode element and at least one inlet and one output port into which cells are introduced and removed from the chamber. Matter carried through the chamber in a fluid stream is then displaced within the fluid by a dielectrophoretic (DEP) force caused by the energized electrode. Following displacement within the fluid, matter travels through the chamber at velocities according to the velocity profile of the chamber. After the matter has transitted through the chamber, it exits at the opposite end of the chamber at a characteristic position.

Abstract: The present disclosure is directed to a novel apparatus and novel methods for the separation, characterization, and manipulation of matter. In particular, the invention combines the use of frequency-dependent dielectric and conductive properties of particulate matter and solubilized matter with the properties of a suspending medium to discriminate and separate such matter. The apparatus includes a chamber having at least one spiral electrode element. Matter is separated in the chamber by a dielectrophoretic (DEP) force caused by the energized electrode or electrodes.

Abstract: The invention relates to a separator, which is particularly useful for separating cellular matter. The separator utilizes the phenomenon known as dielectrophoresis (DEP).A DEP force effects a particle suspended in a medium. The particle experiences a force in an alternating electric field. The force is proportional to, amongst other things, the electrical properties of the supporting medium and the particle and the frequency of the electric field.The separator, of the present invention, comprises a chamber (10) and a plurality of electrodes (12) disposed in the chamber (10).An electric field established across electrodes subjects some of the particles to a stronger force than others such that they are confined within the chamber. Particles which are not confined are removed from the chamber by the supporting medium which is preferably urged through the chamber. Valves (101 and 202) are provided on exhausts of the chamber.The invention is able to separate two different particles continuously.

Abstract: By applying two or more electrical fields (DC, AC, pulsed) of different characteristics to an electrode array on e.g. the wall of a treatment cell, particles suspended in liquid in the cell may be manipulated as desired on a microscopic scale, in particular by exploiting the dielectrophoretic properties of the particles. The particles may be solid, semi-solid or liquid, and may be of simple materials or may be biological particles such as whole cells or fragments thereof.

Abstract: Devices and methods are disclosed for moving charged molecules through a medium by the application of a plurality of electrical fields of sufficient strength and applied for sufficient amounts of time so as to move the charged molecules through the medium. The devices although preferably small in size, preferably generate large numbers (100 or more) of electrical fields to a movement area which preferably contains a liquid buffered or gel medium. Mixtures of charged molecules are pulled through the gel by the force of the electrical fields. The fields are preferably activated simultaneously or sequentially one after another at various speeds to create complex force field distributions or moving field waves along the separation medium. Charged molecules capable of moving quickly through the gel will be moved along by the faster moving field waves and be separated from slower moving molecules.

Abstract: A filter has a conduit having an opening for flow of fluid into the conduit, a pump for pumping fluid into the conduit through the opening, electrodes spaced apart from each other across the opening such that fluid flowing through the opening passes between the electrodes; and an AC electrical source for the electrodes, the source of AC electrical energy having a frequency and voltage such that an electric field created by the AC electrical energy in the area around the electrodes imposes a negative dielectrophoretic force on target particles carried by the fluid, the negative dielectrophoretic force being opposed to the direction of fluid flow through the opening and having sufficient strength to prevent the target particles from passing between the electrodes into the conduit. The filter is mounted in a bioreactor for filtering viable cells and retaining them in culture medium.

Abstract: In order to separate, within a fluid (1), certain particles (2) contained therein, this fluid is arranged in a corridor (C) partly defined by two faces which are close together and substantially parallel to each other and to the direction of separation E and an exciting field is simultaneously applied to the entire volume of fluid contained in this corridor, according to a direction having at least one component perpendicular to the direction E, which exciting field varies along the said direction in a curve consisting of a regular sequence of mutually identical asymmetric patterns, the mean of this field, taken at each instant along the direction E, being zero, and means are provided for repetitively varying the effect of the exciting field on the particles. The substantially parallel faces may be electrodes between which a potential difference source is connected for producing an electric field thereby exciting particles in the corridor (C).

Abstract: Apparatus for separating a mixture of particles comprising a chamber with an inlet and an outlet, means for providing an eluant flow between said inlet and said outlet, within the chamber an electrode structure of at least two electrodes, means for applying an alternating voltage between the electrodes, said electrode structure being such that when energized in operation of the apparatus there is established in the eluant a spatially non-uniform alternating field, whereby particles caused to flow through the chamber in said eluant flow are carried past the electrode structure and are separated into fractions. There may be an ancillary electrode structure of at least two electrodes placed upstream of the main electrode structure with regard to the direction of the flow of fluid. At least one of the electrodes of the electrode structure may be comprised of one or more grid like structures. The electrode structure may be comprised of interleaved grid like structures aligned to obstruct straight through flow.