Abstract: A method of addressing and driving an electrode array includes the step of addressing one or more electrodes within the array using a plurality of row and column lines. In one aspect of the method, a value corresponding to a voltage is stored in a local memory associated with each electrode. The addressed electrodes are then driven at the voltages corresponding to the stored values. In another aspect of the method, a driving element associated with each addressed electrode is selectively coupled with a voltage line so as to charge the electrode with the voltage on the voltage line. The device and methods may be used in the synthesis of biopolymers such as oligonucleotides and peptides.

Abstract: The present invention presents methods for gene expression monitoring that utilize microelectronic arrays to drive the transport and hybridization of nucleic acids. Procedures are described for generating mRNA expression samples for use in these methods from populations of cells, tissues, or other biological source materials, that may differ in their physiological and/or pathological state. Provided in the invention are methods for generating a reusable nucleic acid transcript library from mRNA in a sample of biological material. In order to improve gene expression monitoring on the microelectronic arrays, the transcripts are amplified to produce sample nucleic acid amplicons of a defined length. Because multiple sample amplicons may be selectively hybridized to controlled sites in the electronic array, the gene expression profiles of the polynucleotide populations from different sources can be directly compared in an array format using electronic hybridization methodologies.

Abstract: Methods and apparatus are provided for the analysis and determination of the nature of repeat units in a genetic target. In one method of this invention, the nature of the repeat units in the genetic target is determined by the steps of providing a plurality of hybridization complex assays arrayed on a plurality of test sites, where the hybridization complex assay includes at least a nucleic acid target containing a simple repetitive DNA sequence, a capture probe having a first unique flanking sequence and n repeat units, where n=0,1,2 . . . , or fractions thereof, being complementary to the target sequence, and a reporter probe having a selected sequence complementary to the same target sequence strand wherein the selected sequence of the reporter includes a second unique flanking sequence and m repeat units, where m=0,1,2 . . . , or fractions thereof, but where the sum of repeat units in the capture probe plus reporter probe is greater than 0 (n+m>0).

Abstract: A multilayer, laminated device for performing fluidic operations includes a first exterior support layer, an adjacent layer disposed in laminated relationship with a portion of the exterior support layer, a second exterior support layer disposed in laminated relationship with a portion of the adjacent layer, and a fluidic pump that is disposed in the adjacent layer. The fluidic pump includes a first gear rotationally mounted to the adjacent layer, the first gear having a magnet contained therein. A second gear is rotationally mounted to the adjacent layer, the second gear having a magnet contained therein, the second gear being engaged with the first gear in a meshed relationship.

Abstract: The present invention contemplates chromophore-containing polynucleotides having at least two donor chromophores operatively linked to the polynucleotide by linker arms, such that the chromophores are positioned by linkage along the length of the polynucleotide at a donor-donor transfer distance, and at least one fluorescing acceptor chromophore operatively linked to the polynucleotide by a linker arm, such that the fluorescing acceptor chromophore is positioned by linkage at a donor-acceptor transfer distance from at least one of the donor chromophores, to form a photonic structure for collecting photonic energy and transferring the energy to an acceptor chromophore, and methods using the photonic structures.

Abstract: The present invention pertains to a method of, and a device created by, depositing an inorganic permeation layer on a micro-electronic device for molecular biological reactions. The permeation layer is preferably sol-gel. The sol-gel permeation layer can be created with pre-defined porosity, pore size distribution, pore morphology, and surface area. The sol-gel permeation layer may also function as the attachment layer of the micro-electric device.

Abstract: We have performed separation of bacterial and cancer cells from peripheral human blood in microfabricated electronic chips by dielectrophoresis. The isolated cells were examined by staining the nuclei with fluorescent dye followed by laser induced fluorescence imaging. We have also released DNA and RNA from the isolated cells electronically and detected specific marker sequences by DNA amplification followed by electronic hybridization to immobilized capture probes. Efforts towards the construction of a “laboratory-on-a-chip” system are presented which involves the selection of DNA probes, dyes, reagents and prototyping of the fully integrated portable instrument.

Abstract: This invention relates to devices, methods, and compositions of matter for the multiplex amplification and analysis of nucleic acid sequences in a sample using ligation-dependent strand displacement amplification technologies in combination with bioelectronic microchip technology.

Abstract: Methods and apparatus are provided for the analysis and determination of the nature of repeat units in a genetic target. In one method of this invention, the nature of the repeat units in the genetic target is determined by the steps of providing a plurality of hybridization complex assays arrayed on a plurality of test sites, where the hybridization complex assay includes at least a nucleic acid target containing a simple repetitive DNA sequence, a capture probe having a first unique flanking sequence and n repeat units, where n=0,1,2 . . . , or fractions thereof, being complementary to the target sequence, and a reporter probe having a selected sequence complementary to the same target sequence strand wherein the selected sequence of the reporter includes a second unique flanking sequence and m repeat units, where m=0,1,2 . . . , or fractions thereof, but where the sum of repeat units in the capture probe plus reporter probe is greater than 0 (n+m>0).

Abstract: An optical memory system includes memory cells which utilize synthetic DNA as a component of the information storage mechanism. In the preferred embodiment, memory cells contain one or more chromophoric memory units attached to a support substrate. Each chromophoric memory unit comprises a donor, an acceptor and, at some time during its existence, an active quencher associated with the donor and/or the acceptor. The donor and the acceptor permit non-radiative energy transfer, preferably by Förster energy transfer. To write to the memory cell, the quencher is rendered inactive, preferably by illumination with ultraviolet light. To read, the chromophoric memory units in a read portal are illuminated, and the read illumination is detected. In the preferred embodiment, multiple chromophoric memory units having resolvable read properties are contained within a single read portal. In this way, a multibit word of data may be read from a single diffraction limited read portal.

Abstract: The present invention presents methods for gene expression monitoring that utilize microelectronic arrays to drive the transport and hybridization of nucleic acids. Procedures are described for generating mRNA expression samples for use in these methods from populations of cells, tissues, or other biological source materials, that may differ in their physiological and/or pathological state. Provided in the invention are methods for generating a reusable nucleic acid transcript library from mRNA in a sample of biological material. In order to improve gene expression monitoring on the microelectronic arrays, the transcripts are amplified to produce sample nucleic acid amplicons of a defined length. Because multiple sample amplicons may be selectively hybridized to controlled sites in the electronic array, the gene expression profiles of the polynucleotide populations from different sources can be directly compared in an array format using electronic hybridization methodologies.

Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.

Abstract: A biologic electrode array assembly is formed on an integrated circuit chip that includes an array of electrodes. At least one metal oxide semiconductor (MOS) switch is coupled to at least one of the electrodes within the array. A voltage line is provided that is selectively connected to the at least one electrode via the MOS switch. A voltage source is coupled to the voltage line. In one preferred aspect of the invention, the MOS switch is a CMOS switch. In another aspect of the invention, an addressable memory is associated with the at least one electrode located within the array.

Abstract: Methods of manufacture and devices for performing active biological operations utilize various structures to advantageously collect and provide charged biological materials to an array of microlocations. In one embodiment, a device includes focusing electrodes to aid in the direction and transport of materials from a collection electrode to an array. Preferably, one or more intermediate transportation electrodes are utilized, most preferably of monotonically decreasing size between the collection electrode and the array, so as to reduce current density mismatches. In another aspect, a flow cell is utilized over devices to provide containment of solution containing materials to be analyzed. Preferably, the volume of the flow cell is more advantageously interrogated through use of relatively large collection and return electrodes, such as where the area of those electrodes relative to the footprint of the flowcell is at least 40%.

Abstract: An optical detection system is adapted particularly for detection of biological reactions, especially fluorescent or chemilluminescent reactions. An excitation source, preferably a laser, illuminates a portion of an object to be examined, the portion preferably comprising one microlocation out of an array of microlocations. An intervening optical detection platform serves to direct the excitation radiation, preferably through use of a scanning system, most preferably through use of an x-y mirror-based scanning system to the portion of the object to be illuminated. A detector, preferably a photomultiplier tube, receives the emitted radiation from the objects to be examined, the detector being characterized in that the diameter of the region examined by the detector is the same as or smaller than the diameter of the illuminated region, and comprises less than the entire surface of the object to be examined, and most preferably images a whole or a part of a single microlocation.

Abstract: Devices for performing active biological operations utilize various structures to advantageously collect and provide charged biological materials to an array of microlocations. An active biological matrix device includes an array of unit cells, each unit cell including a variable current control element, a select switch, and a return electrode. The output of the select switch is preferably adapted to contact a conductive solution including charged biological materials. The return electrode is preferably connected to a second potential and adapted to contact the conductive solution. In the presence of the conductive solution, current is provided between the return electrode and the output of the select switch. The variable current control element includes a control element that is adapted to receive a first control signal via, preferably, a first column line. The select switch includes a control element that is adapted to receive a second control signal via, preferably, a first row line.

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: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.

Abstract: An electronic device for performing active biological operations includes a support substrate, a second substrate, a source of illumination, and an edge illumination layer. The support substrate includes first and second surfaces and a via between the first and second surfaces to permit fluid flow through the substrate. The second substrate includes a first surface that is adapted to be disposed in facing arrangement with the second surface of the first substrate. The second substrate includes an array of microlocations wherein the array is adapted to receive the fluid. A sealant is disposed between the second face of the support substrate and the first face of the second substrate. The device includes a source of illumination and an edge illumination layer having an input adapted to receive the illumination from the source, and an output adapted to direct the illumination to the array. The edge illumination layer is disposed adjacent to and between the support substrate and the second substrate.

Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.