Abstract: An assay system and methods are described where patient samples containing genomic DNA are analyzed for the presence of known genetic polymorphisms using a universal reporter strategy. In a preferred embodiment, the amplified DNA is localized at test sites in an array of sites on a microchip followed by a series of hybridization reactions that screen for the presence of a single mutation from among a number of mutations, and allow the identification of specific mutations. In addition to universal reporters, the assay may use blockers and discriminators for screening and identification of known polymorphisms.

Abstract: Methods are provided for the fabrication of microscale, including micron and sub-micron scale, including nanoscale, devices. Electronic transport of movable component devices is utilized through a fluidic medium to effect transport to a desired target location on a substrate or motherboard. Forces include electrophoretic force, electroosmotic force, electrostatic force and/or dielectrophoretic force. In the preferred embodiment, free field electroosmotic forces are utilized either alone, or in conjunction with, other forces. These forces may be used singly or in combination, as well as in conjunction with yet other forces, such as fluidic forces, mechanical forces or thermal convective forces. Transport may be effected through the use of driving electrodes so as to transport the component device to yet other connection electrodes. In certain embodiments, the component devices may be attached to the target device using a solder reflow step.

Abstract: Disclosed herein is a device for measuring fluid dispense volumes including one or more wells adapted to receive a fluid; a tube having an internal passageway fluidly coupled to the one or more wells, wherein fluid in the wells passes into the internal passageway via capillary action to form a fluid column having a meniscus spaced from the wells; and a scale coupled to the tube, the scale calibrated to provide an indication of the volume of the fluid based upon the location of the meniscus in the fluid passageway.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: Methods of addressing a biomolecule to a selectively addressable electrode are described. A permeation layer overlying a plurality of selectively addressable electrodes is provided. The permeation layer includes a reactive group that is adapted to bond to a biomolecule and that requires activation through a chemical transformation before bonding to the biomolecule. At least one selectively addressable electrode is biased such that a pH change occurs in an overlying solution of the at least one selectively addressable electrode. The reactive group in a portion of the permeation layer above the at least one selectively addressable electrode is then chemically transformed to an activated reactive group as a result of the pH change. A biomolecule is then bound to the permeation layer overlying the at least one selectively addressable electrode through the activated reactive group.

Abstract: A method for electronically stabilizing hybridization of nucleic acids bound at a test site of a microelectronic device is described. First and second negatively charged nucleic acids are provided, the second nucleic acid being bound to the test site. A zwitterionic buffer having a conductance of less than 100 mS/cm is applied to the microelectronic device. A current is applied to the test site to positively bias the test site, such that the first negatively charged nucleic acid is transported to the positively biased test site having the bound the second negatively charged nucleic acid. At the test site, the first and second negatively charged nucleic acids hybridize. The zwitterionic buffer acquires a net positive charge under influence of the current, such that the positively charged zwitterionic buffer stabilizes the hybridization by reducing the repulsion between the first and second negatively charged nucleic acids.

Abstract: A method for analyzing nucleic acid obtained from a cell sample on a platform is described. A platform having a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence, is provided. The cell selector is contacted with a cell sample, wherein a portion of the cells remain associated with the cell selector. At least a portion of cells associated with the cell selector are lysed to release a nucleic acid sample. The nucleic acid selector is then contacted with the nucleic acid sample, such that a portion of the nucleic acid sample remains associated with the nucleic acid selector. The associated nucleic acid sample is then released from the nucleic acid selector and then is contacted with the array of microlocations, such that at least a portion of the released nucleic acid sample hybridizes with the capture sequence.

Abstract: The present invention is directed to devices and methods for carrying out and/or monitoring biological reactions in response to electrical stimuli. A programmable multiplexed active biologic array includes an array of electrodes coupled to sample-and-hold circuits. The programmable multiplexed active biologic array includes a digital interface that allows external control of the array using an external processor. The circuit may monitor, digitally control, and deliver electrical stimuli to the electrodes individually or in selected groups.

Abstract: Disclosed herein is a device for measuring fluid dispense volumes including one or more wells adapted to receive a fluid; a tube having an internal passageway fluidly coupled to the one or more wells, wherein fluid in the wells passes into the internal passageway via capillary action to form a fluid column having a meniscus spaced from the wells; and a scale coupled to the tube, the scale calibrated to provide an indication of the volume of the fluid based upon the location of the meniscus in the fluid passageway.

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: A circuit for control of an output current in a multiple unit cell array includes an array of unit cells arranged in rows and columns. Each unit cell includes a column select transistor being adapted for control by a column selector and a row select transistor being adapted for control by a row selector. The column select transistor and the row select transistor are connected together in series to each other and between an output node and a first supply. A return electrode is provided to complete the circuit.

Abstract: A method for electrode-based patterning of thin film, self-assembled nanoparticles. The method uses a variety of types of thin films and electrodes.

Abstract: A system for performing molecular biological diagnosis, analysis and multistep and multiplex reactions utilizes a selfaddressable, selfassembling microelectronic system for actively carrying out controlled reactions in microscopic formats. The device includes a power supply and waveform generator adapted to supply a DC bias and superimposed AC signal to the system through an interface to the array of microlocations.

Abstract: Devices and methods for performing separation of cell particles by dielectrophoresis in three dimensions. In one embodiment the device comprises a flow chamber having microfabricated chip with a plurality of vertical and horizontal electrodes, which may be coated with a protective layer to prevent direct contact between any electrode and a sample. The horizontal electrodes are in electrical communication with a DC or an AC power source, while the vertical electrodes are in electrical communication with an AC power source.

Abstract: An improved synthetic, polymer hydrogel permeation layer for use with an active electronic matrix device for biological assays. The permeation layer includes a dried coating of raffinose or a combination of raffinose and stachyose to protect the permeation layer from degradation during shipping and storage.